ࡱ > RL TL K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K K L L L L L L L L L L
L L L
L L L L L L L L L L L L L L L L L L L L !L "L #L $L %L } bjbj88 R R +Z c+ c+ c+ c+ c+ t + + + , < / l + Ox G1 4 : C4 C4 C4 9 9 9 w w w w w w w , 9| ~ @w c+ 9 9 9 9 9 @w > c+ c+ C4 C4 x > > > 9 r c+ C4 c+ C4 w > 9 w > > N P sz
> O v x 0 Ox .O > ( P > P c+ Y d 9 9 9 @w @w > 9 9 9 Ox 9 9 9 9 9 9 9 9 9 9 9 9 9 + )* :
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR
Francesca Pianaa, David H. Casea, Susana M. Ramalheteb, Giuseppe Pileioa, Marco Facciottia, Graeme M. Daya*, Yaroslav Z. Khimyakb*, Jess Angulob, Richard C. D. Browna and Philip A. Galea*
Eighteen N-aryl-N'-alkyl urea gelators were synthesised in order to understand the effect of head substituents on gelation performance. Minimum gelation concentration values obtained from gel formation studies were used to rank the compounds and revealed the remarkable performance of 4-methoxyphenyl urea gelator 15 in comparison to 4-nitrophenyl analogue 14, which could not be simply ascribed to substituent effects on the hydrogen bonding capabilities of the urea protons. Crystal structure prediction calculations indicated alternative low energy hydrogen bonding arrangements between the nitro group and urea protons in gelator 14, which were supported experimentally by NMR spectroscopy. As a consequence, it was possible to relate the observed differences to interference of the head substituents with the urea tape motif, disrupting the order of supramolecular packing. The combination of unbiased structure prediction calculations with NMR is proposed as a powerful approach to investigate the supramolecular arrangement in gel fibres and help understand the relationships between molecular structure and gel formation.
Introduction
Supramolecular gels, formed by the self-assembly of molecular-scale building blocks, have a wide range of applications.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "978-1-84973-665-7", "author" : [ { "dropping-particle" : "", "family" : "Zweep", "given" : "Niek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Design of Molecular Gelators, Functional Molecular Gels - RSC Soft Matter Series", "editor" : [ { "dropping-particle" : "", "family" : "Escuder", "given" : "Beatriu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miravet", "given" : "Juan F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-26", "publisher" : "The Royal Society of Chemistry", "title" : "The Design of Molecular Gelators", "type" : "chapter" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=846b7a7c-a0de-45a2-892f-3148fecd4e42" ] } ], "mendeley" : { "formattedCitation" : "1", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "1" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }1 Recently, low molecular weight (< 2 kDa) organogelators have attracted attention following the development of polymer gels.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/cr9700282", "author" : [ { "dropping-particle" : "", "family" : "Terech", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Richard G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Reviews", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "1997" ] ] }, "note" : "PMID: 11851487", "page" : "3133-3160", "title" : "Low Molecular Mass Gelators of Organic Liquids and the Properties of Their Gels", "type" : "article-journal", "volume" : "97" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=7257a6b1-2c1c-4415-bcd3-1fa5f34b72a4" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1021/la901720a", "abstract" : "The recent application of supramolecular principles to the design of molecular gelators has led to an enormous variety of new gelators and functional gels but has contributed relatively little to the understanding of molecular gelation phenomena. How do we progress from here?", "author" : [ { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Langmuir", "id" : "ITEM-2", "issue" : "15", "issued" : { "date-parts" : [ [ "2009" ] ] }, "note" : "PMID: 19537740", "page" : "8392-8394", "title" : "We Can Design Molecular Gelators, But Do We Understand Them?", "type" : "article-journal", "volume" : "25" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=47042ea4-aacf-40ab-89dc-6cf19ef9704c" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1039/B417081B", "abstract" : "In recent years there has been immense interest in studying gels derived from low molecular mass gelators (supramolecular{,} or simply molecular gels). The motivation for this is not only to understand the fundamental aggregate structures in the gels at different length scales{,} but also to explore their potential for futuristic technological applications. Gels have been made sensitive to external stimuli like light and chemical entities by incorporating a spectroscopically active or a receptor unit as part of the gelator molecule. This makes them suitable for applications such as sensing and actuating. The diversity of gel structural architectures has allowed them to be utilized as templates to prepare novel inorganic superstructures for possible applications in catalysis and separation. Gels derived from liquid crystals (anisotropy gels) that can act as dynamically functional materials have been prepared{,} for example{,} for (re-writable) information recording. Supramolecular gels can be important in controlled release applications{,} in oil recovery{,} for gelling cryogenic fuels etc. They can also serve as media for a range of applications. This tutorial review highlights some of the instructive work done by various groups to develop smart and functional gels{,} and covers a wide spectrum of scientific interest ranging from medicine to materials science.", "author" : [ { "dropping-particle" : "", "family" : "Sangeetha", "given" : "Neralagatta M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maitra", "given" : "Uday", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem. Soc. Rev.", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "821-836", "publisher" : "The Royal Society of Chemistry", "title" : "Supramolecular gels: Functions and uses", "type" : "article-journal", "volume" : "34" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=2925918c-8e61-4a72-b089-c1c7725c0338" ] } ], "mendeley" : { "formattedCitation" : "2\u20134", "plainTextFormattedCitation" : "2\u20134", "previouslyFormattedCitation" : "2\u20134" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }24 The late development of this area can be explained by the serendipitous nature of the discovery of new gelators.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/jo502915w", "ISSN" : "0022-3263", "abstract" : "Small molecule gelators are serendipitously discovered more often than they are designed. As a consequence, it has been challenging to develop applications based on the limited set of known materials. This synopsis highlights recent strategies to streamline the process of gelator discovery, with a focus on the role of unidirectional intermolecular interactions and solvation. We present these strategies as a series of tools that can be employed to help identify gelator scaffolds and solvents for gel formation. Overall, we suggest that this guided approach is more efficient than random derivatization and screening.", "author" : [ { "dropping-particle" : "", "family" : "Zurcher", "given" : "Danielle M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNeil", "given" : "Anne J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Organic Chemistry", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015", "3", "6" ] ] }, "note" : "doi: 10.1021/jo502915w", "page" : "2473-2478", "publisher" : "American Chemical Society", "title" : "Tools for Identifying Gelator Scaffolds and Solvents", "type" : "article-journal", "volume" : "80" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=cadd1f71-8ad2-4889-80a6-7c7c905bba40" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1021/ja503363v", "abstract" : "A Perspective is presented on the history and current understanding of molecular gels and the factors that must be considered to characterize them. The abilities of the most important structural, dynamic, and rheological tools available currently to provide the information necessary to follow the formation of a molecular gel from its initial sol phase and then to define it at different distance and time scales are discussed. Approaches to determining a priori when a molecule will gelate a selected liquid, as well as possible methodologies for overcoming current limitations in understanding molecular gels, are presented. Finally, some of the many potential and realized applications for these materials are enumerated.", "author" : [ { "dropping-particle" : "", "family" : "Weiss", "given" : "Richard G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Chemical Society", "id" : "ITEM-2", "issue" : "21", "issued" : { "date-parts" : [ [ "2014" ] ] }, "note" : "PMID: 24836858", "page" : "7519-7530", "title" : "The Past, Present, and Future of Molecular Gels. What Is the Status of the Field, and Where Is It Going?", "type" : "article-journal", "volume" : "136" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=75c6826d-5fd4-477f-85c9-173be1183933" ] } ], "mendeley" : { "formattedCitation" : "5,6", "plainTextFormattedCitation" : "5,6", "previouslyFormattedCitation" : "5,6" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }5,6 Despite much effort, the gelation process of low molecular weight organogelators is still not fully understood.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/1521-3765(20000717)6:14<2633::AID-CHEM2633>3.0.CO;2-L", "ISSN" : "1521-3765", "author" : [ { "dropping-particle" : "", "family" : "Schoonbeek", "given" : "Franck S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hulst", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kellogg", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feringa", "given" : "Ben L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry - A European Journal", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "2633-2643", "publisher" : "WILEY-VCH Verlag", "title" : "Geminal Bis-ureas as Gelators for Organic Solvents: Gelation Properties and Structural Studies in Solution and in the Gel State", "type" : "article-journal", "volume" : "6" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=e6f369e8-f702-4627-b08f-7c8aeef2f587" ] } ], "mendeley" : { "formattedCitation" : "7", "plainTextFormattedCitation" : "7", "previouslyFormattedCitation" : "7" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }7 In particular, the correlation between precursor composition, assembly conditions and self-assembled structure remains unclear. As a consequence, many researchers have identified new gelators simply by modifying known scaffolds.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4SM01389A", "abstract" : "We explore the formation and structure of gels produced from solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide (DMSO). Mixing these solutions with water results in the self-assembly of Fmoc-FF molecules into space-filling fibrous networks{,} exhibiting mechanical properties characteristic of gels. Using confocal fluorescence microscopy{,} we observe the gel transition in situ and find that{,} upon the addition of water{,} the solution undergoes a rapid transition to a non-equilibrium state forming [similar]2 [small mu ]m spheres{,} followed by the formation of fibers 5-10 nm in diameter{,} nucleating at a sphere surface and expanding into the solution as the remaining spheres dissolve{,} extending the network. The gel aging process is associated with the network becoming increasingly uniform through apparent redissolution/reaggregation of the Fmoc-FF molecules{,} corresponding to the observed increase in the elastic modulus to a plateau value. We demonstrate that this increase in uniformity and elastic modulus can be expedited by controlling the temperature of the system{,} as well as that these gels are thermally reversible{,} further indicating that the system is in equilibrium in its fibrous network state. X-ray scattering information suggests that the packing of the molecules within a fiber is based on [small pi]-[small pi] stacking of [small beta]-sheets{,} consistent with models proposed in the literature for similar systems{,} implying that each particle (molecule) possesses a limited number of interaction sites. These observations provide experimental evidence that these low molecular weight gelator molecules can be considered valence-limited {", "author" : [ { "dropping-particle" : "", "family" : "Dudukovic", "given" : "Nikola A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zukoski", "given" : "Charles F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "39", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "7849-7856", "publisher" : "The Royal Society of Chemistry", "title" : "Evidence for equilibrium gels of valence-limited particles", "type" : "article-journal", "volume" : "10" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=bb495a10-9b6d-4d0c-a823-8a99b3511ff8" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/C3RA44070B", "abstract" : "Gel formation by low molecular mass gelators was investigated. The gelator was trans(RR)- or trans(SS)-N{,}N[prime or minute]-n-bromoalkanoyl-1{,}2-diaminocyclohexane (denoted as RR-CnBr or SS-CnBr{,} respectively; n = the number of carbon atoms in an alkanoyl group). When n was varied from 5 to 12{,} the gelators formed transparent or opaque or turbid gels in benzene except for n = 8. Focusing on the end effects{,} the gelation behavior of CnBr was compared with that of non-brominated counterparts (denoted as RR- or SS-Cn). From the vibrational circular dichroism (VCD) spectra of enantiomeric gelator/benzene-d6 gels{,} the signs of the coupled peaks around 1640 cm-1{,} which were assigned to the symmetric and asymmetric C[double bond{,} length as m-dash]O stretching vibrations from the higher to lower wavenumber{,} respectively{,} were opposite between SS-CnBr and SS-Cn (or between RR-CnBr and RR-Cn). On the other hand{,} the signs of the coupled peaks around 1550 cm-1 assigned to the NH stretching vibrations remained unaffected. The observed reversal of the signs in the C[double bond{,} length as m-dash]O couplet was rationalized in terms of the different modes of stacking in fibrils. In the case of Cn{,} for example{,} the molecules were stacked through anti-parallel double intermolecular hydrogen bonds using two pairs of >NH and >C[double bond{,} length as m-dash]O groups{,} while{,} in the case of CnBr{,} a single intermolecular hydrogen bond was formed with the remaining pair of >NH and >C[double bond{,} length as m-dash]O groups forming an intramolecular hydrogen bond. Single crystal X-ray analyses were performed for SS-C6Br and SS-C8Br. The results demonstrated that the length of the bromoalkanoyl chains drastically affected the packing modes in crystalline states.", "author" : [ { "dropping-particle" : "", "family" : "Sato", "given" : "Hisako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nogami", "given" : "Emiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajima", "given" : "Tomoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamagishi", "given" : "Akihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RSC Adv.", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1659-1665", "publisher" : "The Royal Society of Chemistry", "title" : "Terminal effects on gelation by low molecular weight chiral gelators", "type" : "article-journal", "volume" : "4" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=c9fc5d03-242d-4777-920e-e73450852899" ] } ], "mendeley" : { "formattedCitation" : "8,9", "plainTextFormattedCitation" : "8,9", "previouslyFormattedCitation" : "8,9" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }8,9 However, the approach of taking known gelators and tuning them for a specific purpose is limited by the systems available and solvents required for effective gelation, which may further limit the scope of application.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/jo502915w", "ISSN" : "0022-3263", "abstract" : "Small molecule gelators are serendipitously discovered more often than they are designed. As a consequence, it has been challenging to develop applications based on the limited set of known materials. This synopsis highlights recent strategies to streamline the process of gelator discovery, with a focus on the role of unidirectional intermolecular interactions and solvation. We present these strategies as a series of tools that can be employed to help identify gelator scaffolds and solvents for gel formation. Overall, we suggest that this guided approach is more efficient than random derivatization and screening.", "author" : [ { "dropping-particle" : "", "family" : "Zurcher", "given" : "Danielle M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNeil", "given" : "Anne J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Organic Chemistry", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015", "3", "6" ] ] }, "note" : "doi: 10.1021/jo502915w", "page" : "2473-2478", "publisher" : "American Chemical Society", "title" : "Tools for Identifying Gelator Scaffolds and Solvents", "type" : "article-journal", "volume" : "80" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=cadd1f71-8ad2-4889-80a6-7c7c905bba40" ] } ], "mendeley" : { "formattedCitation" : "5", "plainTextFormattedCitation" : "5", "previouslyFormattedCitation" : "5" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }5 An increased understanding of the relationship between molecular and self-assembled structure would not only represent a significant scientific advance, but also enable the design of new gel-based materials.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4SM02532F", "abstract" : "Low molecular weight hydrogels are formed by molecules that form a matrix that immobilises water to form a self-supporting gel. Such gels have uses as biomaterials such as molecular scaffolds and structures for tissue engineering. One class of low molecular weight gelator (LMWG){,} naphthalene-conjugated dipeptides{,} has been shown to form hydrogels via self-assembly following a controlled drop in pH. A library of naphthalene-dipeptides has been generated previously although the relationship between the precursor sequence and the resulting self-assembled structures remained unclear. Here{,} we have investigated the structural details of a set of dipeptide sequences containing alanine (A) and valine (V) conjugated to naphthalene groups substituted with a Br{,} CN or H at the 6-position. Electron microscopy{,} circular dichroism and X-ray fibre diffraction shows that these LMWG may be structurally classified by their composition: the molecular packing is determined by the class of conjugate{,} whilst the chirality of the self-assemblies can be attributed to the dipeptide sequence. This provides insights into the relationship between the precursor sequence and the macromolecular and molecular structures of the fibres that make up the resulting hydrogels.", "author" : [ { "dropping-particle" : "", "family" : "Morris", "given" : "Kyle L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodger", "given" : "Alison", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "Dave J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serpell", "given" : "Louise C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1174-1181", "publisher" : "The Royal Society of Chemistry", "title" : "Structural determinants in a library of low molecular weight gelators", "type" : "article-journal", "volume" : "11" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=615f80c8-124a-449c-9174-fa8b0224ad2b" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }10
At around the same time, Hanabusa,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1246/cl.1996.885", "author" : [ { "dropping-particle" : "", "family" : "Hanabusa", "given" : "Kenji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimura", "given" : "Kouji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Kazunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kimura", "given" : "Mutsumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirai", "given" : "Hirofusa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry Letters", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "885-886", "title" : "Formation of Organogels by Intermolecular Hydrogen Bonding between Ureylene Segment", "type" : "article-journal", "volume" : "25" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=f35af723-b93b-45e3-a324-40309ad8389d" ] } ], "mendeley" : { "formattedCitation" : "11", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "11" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }11 van Esch and KelloggADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "http://dx.doi.org/10.1016/S0040-4039(96)02292-7", "ISSN" : "0040-4039", "abstract" : "Simple diurea compounds form thermoreversible gels with several organic solvents. These gels are stable up to temperatures of 100\u00b0C, and can be stored for months. Electron microscopy reveals that in these solvents the gelation agents assemble into very thin rectangular sheets which are several tens of micrometers long.", "author" : [ { "dropping-particle" : "", "family" : "Esch", "given" : "Jan", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kellogg", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feringa", "given" : "Ben L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Tetrahedron Letters", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-284", "title" : "Di-urea compounds as gelators for organic solvents", "type" : "article-journal", "volume" : "38" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=8d0b293f-6b60-43f4-bc47-b1657a8f3bc5" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/chem.19970030811", "ISSN" : "1521-3765", "author" : [ { "dropping-particle" : "", "family" : "Esch", "given" : "Jan", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feyter", "given" : "Steven", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kellogg", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schryver", "given" : "Frans", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feringa", "given" : "Ben L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry - A European Journal", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "1238-1243", "publisher" : "WILEY-VCH Verlag", "title" : "Self-Assembly of Bisurea Compounds in Organic Solvents and on Solid Substrates", "type" : "article-journal", "volume" : "3" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=31720186-aeb0-478f-8d78-216f89df07ae" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/1521-3765(20000717)6:14<2633::AID-CHEM2633>3.0.CO;2-L", "ISSN" : "1521-3765", "author" : [ { "dropping-particle" : "", "family" : "Schoonbeek", "given" : "Franck S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hulst", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kellogg", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feringa", "given" : "Ben L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry - A European Journal", "id" : "ITEM-3", "issue" : "14", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "2633-2643", "publisher" : "WILEY-VCH Verlag", "title" : "Geminal Bis-ureas as Gelators for Organic Solvents: Gelation Properties and Structural Studies in Solution and in the Gel State", "type" : "article-journal", "volume" : "6" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=e6f369e8-f702-4627-b08f-7c8aeef2f587" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/(SICI)1521-3765(19990301)5:3<937::AID-CHEM937>3.0.CO;2-0", "ISSN" : "0947-6539", "author" : [ { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoonbeek", "given" : "Franck", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Maaike", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooijman", "given" : "Huub", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spek", "given" : "Anthony L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kellogg", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feringa", "given" : "Ben L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry - A European Journal", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "3", "1" ] ] }, "page" : "937-950", "publisher" : "WILEY-VCH Verlag", "title" : "Cyclic Bis-Urea Compounds as Gelators for Organic Solvents", "type" : "article-journal", "volume" : "5" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=cb6b85a8-9ad6-4c3b-9252-b7d82763f8a9" ] } ], "mendeley" : { "formattedCitation" : "7,12\u201314", "plainTextFormattedCitation" : "7,12\u201314", "previouslyFormattedCitation" : "7,12\u201314" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }7,1214 have independently exploited urea derivatives to obtain new gelators, where the urea motif represents the molecular equivalent of a Velcro type hook-and-loop.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/B926219A", "ISSN" : "0306-0012", "abstract" : "This tutorial review looks at the formation of low molecular weight gels from molecular principles using the well-explored supramolecular chemistry of ureas as an example. Synthesising lessons learned from classical urea inclusion chemistry, ureas in crystal engineering, ureas in self-assembly, urea functional groups in anion binding and sensing, and ureas as organocatalysts lead to the development and understanding of a new class of anion-tunable, urea-based soft materials. This review concludes with a look at emerging application areas for tunable gel-phase materials as controlled crystal growth media, both in templating metallic nanoparticles and in the growth and isolation of high quality crystals of molecular organic compounds, including polymorphic pharmaceuticals.", "author" : [ { "dropping-particle" : "", "family" : "Steed", "given" : "Jonathan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Society Reviews", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "3686-3699", "publisher" : "The Royal Society of Chemistry", "title" : "Anion-tuned supramolecular gels: a natural evolution from urea supramolecular chemistry", "type" : "article-journal", "volume" : "39" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=849d7b04-da98-41f9-958d-cbefeb52c1d4" ] } ], "mendeley" : { "formattedCitation" : "15", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "15" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }15 This enabled molecular unidirectional self-association and, for this reason, the urea motif has been extensively used to form supramolecular assemblies. Further developments followed with the increasing awareness that gelation can be considered a kinetically-trapped phase of matter, even in molecular modelling, when compared with the thermodynamic crystalline phase.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C0SM00409J", "abstract" : "Predicting the ability of low molecular weight molecules to form hydrogels is difficult. Here{,} we have examined the self-assembly behavior of two chemically and structurally similar functionalized dipeptides{,} one of which is found to form a meta-stable hydrogel (1) and the other forming a crystalline solid (2). To investigate the reasons for these differences{,} we have employed computational methods to explore the crystal energy landscapes of the two molecules and examined differences in their preferred packing arrangements. We show that this method accurately predicts the packing for the crystalline solid{,} 2. Furthermore{,} the predictions for the gel-former 1 suggest that one-dimensional hydrogen-bonding arranged into tightly coiled molecular columns is a preferred mode of packing for this system{,} but is unfavorable for 2. The different tendencies of forming these columns could provide an explanation for the different behavior of the two molecules and demonstrate that this approach could be useful for the future predictable design of low molecular weight gelators.", "author" : [ { "dropping-particle" : "", "family" : "Adams", "given" : "Dave J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Kyle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serpell", "given" : "Louise C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacsa", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "4144-4156", "publisher" : "The Royal Society of Chemistry", "title" : "The delicate balance between gelation and crystallisation: structural and computational investigations", "type" : "article-journal", "volume" : "6" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=bd455810-e557-4e3d-b11b-cca2d2867e32" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/anie.200703785", "ISSN" : "1521-3773", "author" : [ { "dropping-particle" : "", "family" : "Anderson", "given" : "Kirsty M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "Martin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byrne", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Nigel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steed", "given" : "Jonathan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Angewandte Chemie International Edition", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1058-1062", "publisher" : "WILEY-VCH Verlag", "title" : "Structure Calculation of an Elastic Hydrogel from Sonication of Rigid Small Molecule Components", "type" : "article-journal", "volume" : "47" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=453b1d5f-7a32-48ab-9e1c-8f145e3094a4" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1021/la050655j", "abstract" : "Mixtures of derivatives of Hanabusa's bolaamphiphilic amidocarbamates containing two Z-valinyl subunits and aliphatic spacers that range from ethylenic to octamethylenic are able to form organogels. A coassembly of them is observed in their acetonitrile and toluene gels; namely, the concentration of a given compound at which a gel is formed is lowered by the presence of equimolar quantities of any other compound in the series. The aggregates were studied by wide-angle X-ray diffraction (WAXD) and the results can be rationalized if the gel fibers are formed by supramolecular copolymers. NMR studies reveal that in solution these molecules adopt folded conformations containing intramolecular H-bonds, but IR studies indicate that these are not present in their aggregates. Additionally, analogues of the amidocarbamates obtained by replacement of the carbamate functionality by amide have been shown to behave in a similar way. For these molecules it can be shown that the central aliphatic subunit is not completely extended in the conformations present in the aggregates according to IR and WAXD studies. The tetraamide-type compounds described are robust organogelators that form gels in a variety of organic solvents with good thermostability and present improved feasibility for the synthesis of envisaged functional organogelators.", "author" : [ { "dropping-particle" : "", "family" : "Escuder", "given" : "Beatriu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ed", "given" : "Santiago", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miravet", "given" : "Juan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Langmuir", "id" : "ITEM-3", "issue" : "15", "issued" : { "date-parts" : [ [ "2005" ] ] }, "note" : "PMID: 16008387", "page" : "6776-6787", "title" : "Organogel Formation by Coaggregation of Adaptable Amidocarbamates and Their Tetraamide Analogues", "type" : "article-journal", "volume" : "21" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=ad17ac25-891a-4888-acc2-1b03532e0b37" ] } ], "mendeley" : { "formattedCitation" : "16\u201318", "plainTextFormattedCitation" : "16\u201318", "previouslyFormattedCitation" : "16\u201318" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }1618 With this knowledge, functional groups began to be used as a means to manipulate the solubility parameters of gelators (e.g. long alkyl chain in polar solvents), allowing access to this metastable state and taking advantage of the modified solute-solvent interactions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C0SM00843E", "abstract" : "By studying a family of l-lysine bis-urea gelators with variable peripheral groups in different solvents{,} a more detailed understanding of the way in which gelator fibres interact with the surrounding solvent environment is obtained. In all cases{,} these gelators establish the same hydrogen bonding molecular recognition pathways-however{,} this process is mediated by the nature of the solvent. In terms of Kamlet-Taft parameters{,} the [small alpha] parameter of the solvent (hydrogen bond donor ability) has primary importance in controlling whether the gelator can establish a hydrogen bond network; the [small beta] parameter (hydrogen bond acceptor ability) plays a secondary role in tuning the thermal stability of the gel{,} and the [small pi]* parameter (polarisability) controls the solvation of the peripheral groups on the gelator by the solvent{,} and hence tunes the gel stability and the ability of the gelator to establish fibre-fibre interactions{,} as evidenced by scanning electron microscopy imaging. Considering solvent parameters allows us to gain a unique insight into hierarchical assembly processes at different length scales{,} i.e.{,} molecular scale gelator-gelator interactions{,} and nanoscale fibre-fibre and fibre-solvent interactions. These processes are at the heart of developing effective models for the dynamic assembly of gel-phase soft materials.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagadec", "given" : "Cecile A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "David K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "110-117", "publisher" : "The Royal Society of Chemistry", "title" : "Solvent-gelator interactions-using empirical solvent parameters to better understand the self-assembly of gel-phase materials", "type" : "article-journal", "volume" : "7" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=8919f90f-e42a-4538-b946-93585a362ced" ] } ], "mendeley" : { "formattedCitation" : "19", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "19" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }19 These and many other studies during the past twenty years contributed to the formulation of three basic rulesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "978-1-84973-665-7", "author" : [ { "dropping-particle" : "", "family" : "Zweep", "given" : "Niek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Design of Molecular Gelators, Functional Molecular Gels - RSC Soft Matter Series", "editor" : [ { "dropping-particle" : "", "family" : "Escuder", "given" : "Beatriu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miravet", "given" : "Juan F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-26", "publisher" : "The Royal Society of Chemistry", "title" : "The Design of Molecular Gelators", "type" : "chapter" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=846b7a7c-a0de-45a2-892f-3148fecd4e42" ] } ], "mendeley" : { "formattedCitation" : "1", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "1" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }1 for designing low molecular weight gelators: 1) the existence of unidirectional intermolecular interactions to favour one-dimensional self-assembly; 2) intertwining of the aggregates for network formation, and 3) the control of fibre/solvent interfacial energy to manipulate solubility and prevent the crystallisation of the metastable gel.
The original aim of this work was to extend the understanding of molecular structure-gelation relationships by systematically varying some molecular features of a common scaffold, as exemplified in Fig. 1, in order to isolate the contribution of NO2 and OCH3 head substituents on a phenyl ring. Gelation test outcomes have driven the series of structural modifications that led to the synthesis of a total of eighteen analogues. As a consequence of the unusual observations made and in an effort to understand them, two representative gelators (14 and 15) underwent more comprehensive thermo-mechanical characterisation, molecular modelling and NMR studies.
Fig. 1 Schematic representation of the urea scaffold investigated.
Results and discussion
Synthesis of the gelators
Compounds 118 were synthesized and all products precipitated as solids and were isolated in moderate to good yields.
1 R = H; n = 5 (92%)
2 R = NO2; n = 5 (50%)
3 R = OCH3; n = 5 (95%)
4 R = H; n = 10 (69%)
5 R = NO2; n = 10 (72%)
6 R = OCH3; n = 10 (86%)
7 R = H; n = 11 (100%)
8 R = NO2; n = 11 (59%)
9 R = OCH3; n = 11 (89%)
10 R = H; n = 12 (100%)
11 R = NO2; n = 12 (63%)
12 R = OCH3; n = 12 (100%)
13 R = H; n = 13 (98%)
14 R = NO2; n = 13 (85%)
15 R = OCH3; n = 13 (98%)16 (77%)
17 (72%)
18 (100%)Gelation studies
Gel formation studies were performed in fifteen solvents, chosen in order to cover a wide range of polarities from hexane to water. Gelators were tested at nine different concentrations (5, 10, 15, 20, 30, 40, 50, 100, 150 mg mL1). The threshold concentration of 20 mg mL1 was that from which all gel formation studies commenced. If a gel was formed at this concentration, further tests at lower concentration (15, 10, 5 mg mL1) were performed. If the result was the formation of a partial gel, more tests were conducted at higher concentration (30, 40, 50, 100, 150 mg mL1) in an attempt to form a gel. No further tests were carried out when no gel or insolubility was observed. Although a wide range of gelation solvents were tested, solvent polarity was found not to directly affect (or at least straightforwardly) gelation performance, despite reported evidence on other systems.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C5CS00136F", "ISSN" : "0306-0012", "author" : [ { "dropping-particle" : "", "family" : "Lan", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corradini", "given" : "M. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "R. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raghavan", "given" : "S. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rogers", "given" : "M. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem. Soc. Rev.", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "6035-6058", "title" : "To gel or not to gel: correlating molecular gelation with solvent parameters", "type" : "article-journal", "volume" : "44" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=43d32cd9-aff5-464c-b74a-93a9dd20b01e" ] } ], "mendeley" : { "formattedCitation" : "20", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "20" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }20 For this reason, it was decided to concentrate on three solvents: toluene, tetralin and dimethyl sulfoxide. Gelation performances of 118 were then ranked with respect to the minimum gelation concentration (MGC) values in these three solvents (Table 1).
Table 1 Minimum gelation concentration (MGC) values for gelators 118 in toluene, tetralin and dimethyl sulfoxide.
MGC (mg mL1)GelatorTolueneTetralinDimethyl sulfoxide1n.g.n.g.n.g.2n.g.n.g.n.g.3n.g.n.g.n.g.4i.> 150n.g.5i.20n.g.63030n.g.7100100n.g.830i.n.g.9i.153010i.40n.g.11i.30n.g.122015100131015301420205015555016i.i.4017n.g.n.g.i.18201520n.g. stands for no gel and i. insoluble results.
Gelators 13 bearing short alkyl chains did not form any gels due to their high solubility, indicating that solute-solvent interactions prevailed over the solute-solute interactions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C3SM52297K", "abstract" : "Many small molecules can self-assemble by non-covalent interactions into fibrous networks and thereby induce gelation of organic liquids. However{,} no capability currently exists to predict whether a molecule in a given solvent will form a gel{,} a low-viscosity solution (sol){,} or an insoluble precipitate. Gelation has been recognized as a phenomenon that reflects a balance between solubility and insolubility; however{,} the distinction between these regimes has not been quantified in a systematic fashion. In this work{,} we focus on a well-known gelator{,} 1{,}3:2{,}4-dibenzylidene sorbitol (DBS){,} and study its self-assembly in various solvents. From these data{,} we build a framework for DBS gelation based on Hansen solubility parameters (HSPs). While the HSPs for DBS are not known a priori{,} the HSPs are available for each solvent and they quantify the solvent{'}s ability to interact via dispersion{,} dipole-dipole{,} and hydrogen bonding interactions. Using the three HSPs{,} we construct three-dimensional plots showing regions of solubility (S){,} slow gelation (SG){,} instant gelation (IG){,} and insolubility (I) for DBS in the different solvents at a given temperature and concentration. Our principal finding is that the above regions radiate out as concentric shells: i.e.{,} a central solubility (S) sphere{,} followed in order by spheres corresponding to SG{,} IG{,} and I regions. The distance (R0) from the origin of the central sphere quantifies the incompatibility between DBS and a solvent-the larger this distance{,} the more incompatible the pair. The elastic modulus of the final gel increases with R0{,} while the time required for a super-saturated sol to form a gel decreases with R0. Importantly{,} if R0 is too small{,} the gels are weak{,} but if R0 is too large{,} insolubility occurs-thus{,} strong gels fall within an optimal window of incompatibility between the gelator and the solvent. Our approach can be used to design organogels of desired strength and gelation time by judicious choice of a particular solvent or a blend of solvents. The above framework can be readily extended to many other gelators{,} including those with molecular structures very different from that of DBS. We have developed a MATLAB program that will be freely available (upon request) to the scientific community to replicate and extend this approach to other gelators of interest.", "author" : [ { "dropping-particle" : "", "family" : "Diehn", "given" : "Kevin K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oh", "given" : "Hyuntaek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashemipour", "given" : "Reza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Richard G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raghavan", "given" : "Srinivasa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2632-2640", "publisher" : "The Royal Society of Chemistry", "title" : "Insights into organogelation and its kinetics from Hansen solubility parameters. Toward a priori predictions of molecular gelation", "type" : "article-journal", "volume" : "10" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=58d4cae0-9f7b-4d8c-9820-1d8d87d663bc" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/anie.200301739", "ISSN" : "1521-3773", "abstract" : "Molecular recognition events in solution are affected by many different factors that have hampered the development of an understanding of intermolecular interactions at a quantitative level. Our tendency is to partition these effects into discrete phenomenological fields that are classified, named, and divorced: aromatic interactions, cation\u2013\u03c0 interactions, CH\uf8ffO hydrogen bonds, short strong hydrogen bonds, and hydrophobic interactions to name a few.1 To progress in the field, we need to develop an integrated quantitative appreciation of the relative magnitudes of all of the different effects that might influence the molecular recognition behavior of a given system. In an effort to navigate undergraduates through the vast and sometimes contradictory literature on the subject, I have developed an approach that treats theoretical ideas and experimental observations about intermolecular interactions in the gas phase, the solid state, and solution from a single simplistic viewpoint. The key features are outlined here, and although many of the ideas will be familiar, the aim is to provide a semiquantitative thermodynamic ranking of these effects in solution at room temperature.", "author" : [ { "dropping-particle" : "", "family" : "Hunter", "given" : "Christopher A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Angewandte Chemie International Edition", "id" : "ITEM-2", "issue" : "40", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "5310-5324", "publisher" : "WILEY-VCH Verlag", "title" : "Quantifying Intermolecular Interactions: Guidelines for the Molecular Recognition Toolbox", "type" : "article-journal", "volume" : "43" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=07e1c7ba-52fc-48d8-82cb-f440e980d5b9" ] } ], "mendeley" : { "formattedCitation" : "21,22", "plainTextFormattedCitation" : "21,22", "previouslyFormattedCitation" : "21,22" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }21,22 Evidently, the relatively short alkyl chain (C6) was insufficient to provide enough solvophobic drive, with a weak contribution to chain packing through van der Waals interactions.
In an effort to optimise gelation performance, the number of carbon atoms in the chain was increased (C11C14) in 415. Notably, it was more difficult to obtain gels in toluene in the presence of an odd numbered alkyl chain, while the presence of the even numbered C14 chain yielded the best performance in both toluene and tetralin. Additionally, no gels were formed in dimethyl sulfoxide until the alkyl chain was sufficiently long. Consequently, C14 alkyl chain analogues were chosen to study the substituent interference on the self-assembly of the class of molecules investigated in this work.
Since the inclusion of the C14 apolar moiety in 1315 was shown to be sufficient to promote either gelation or lower MGC values and literature reports show that long n-alkanes can provide gels of remarkable stability in organic solvents,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/la990795r", "abstract" : "Thermoreversible gelation of relatively short n-alkanes and a variety of other organic liquids has been accomplished using low concentrations of long n-alkanes (chain lengths from 24 to 36 carbon atoms) as gelators. The stability of the gels is discussed in terms of gelator concentration, gelation temperature, and the duration of time gels persist without bulk phase separation. Generally, stability increases with the chain length of the gelator. n-Alkanes are structurally the simplest organic gelators possible and their gels with n-alkanes as liquids are the simplest organogels that can be made. Their existence demonstrates that London dispersion forces alone can provide colloidal networks whose strength is sufficient to immobilize liquids against the pull of gravity.", "author" : [ { "dropping-particle" : "", "family" : "Abdallah", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Richard G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Langmuir", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "352-355", "title" : "n-Alkanes Gel n-Alkanes (and Many Other Organic Liquids)", "type" : "article-journal", "volume" : "16" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=05d26d77-3da5-4fac-a250-e8f90393536e" ] } ], "mendeley" : { "formattedCitation" : "23", "plainTextFormattedCitation" : "23", "previouslyFormattedCitation" : "23" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }23 gelator 18 was designed and found to exhibit low MGC values (1520 mg mL1).
Finally, to confirm the importance of the urea hydrogen bonding motif for this scaffold, one or both urea hydrogen bonding donor sites were removed in 16 (amide) and 17 (ester). Poor gelation observed was attributed to the either extremely low or high solubility of 16 and 17, respectively, incompatible with the required balance between solute-solute and solute-solvent interactions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C3SM52297K", "abstract" : "Many small molecules can self-assemble by non-covalent interactions into fibrous networks and thereby induce gelation of organic liquids. However{,} no capability currently exists to predict whether a molecule in a given solvent will form a gel{,} a low-viscosity solution (sol){,} or an insoluble precipitate. Gelation has been recognized as a phenomenon that reflects a balance between solubility and insolubility; however{,} the distinction between these regimes has not been quantified in a systematic fashion. In this work{,} we focus on a well-known gelator{,} 1{,}3:2{,}4-dibenzylidene sorbitol (DBS){,} and study its self-assembly in various solvents. From these data{,} we build a framework for DBS gelation based on Hansen solubility parameters (HSPs). While the HSPs for DBS are not known a priori{,} the HSPs are available for each solvent and they quantify the solvent{'}s ability to interact via dispersion{,} dipole-dipole{,} and hydrogen bonding interactions. Using the three HSPs{,} we construct three-dimensional plots showing regions of solubility (S){,} slow gelation (SG){,} instant gelation (IG){,} and insolubility (I) for DBS in the different solvents at a given temperature and concentration. Our principal finding is that the above regions radiate out as concentric shells: i.e.{,} a central solubility (S) sphere{,} followed in order by spheres corresponding to SG{,} IG{,} and I regions. The distance (R0) from the origin of the central sphere quantifies the incompatibility between DBS and a solvent-the larger this distance{,} the more incompatible the pair. The elastic modulus of the final gel increases with R0{,} while the time required for a super-saturated sol to form a gel decreases with R0. Importantly{,} if R0 is too small{,} the gels are weak{,} but if R0 is too large{,} insolubility occurs-thus{,} strong gels fall within an optimal window of incompatibility between the gelator and the solvent. Our approach can be used to design organogels of desired strength and gelation time by judicious choice of a particular solvent or a blend of solvents. The above framework can be readily extended to many other gelators{,} including those with molecular structures very different from that of DBS. We have developed a MATLAB program that will be freely available (upon request) to the scientific community to replicate and extend this approach to other gelators of interest.", "author" : [ { "dropping-particle" : "", "family" : "Diehn", "given" : "Kevin K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oh", "given" : "Hyuntaek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashemipour", "given" : "Reza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Richard G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raghavan", "given" : "Srinivasa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2632-2640", "publisher" : "The Royal Society of Chemistry", "title" : "Insights into organogelation and its kinetics from Hansen solubility parameters. Toward a priori predictions of molecular gelation", "type" : "article-journal", "volume" : "10" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=58d4cae0-9f7b-4d8c-9820-1d8d87d663bc" ] } ], "mendeley" : { "formattedCitation" : "21", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "21" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }21
Inspection of the MCG values for gelators 1315 indicated that the presence of the head substituent OCH3 led to better performance (5 mg mL1) than NO2 (20 mg mL1). Gelation driven by cooperative hydrogen bonding between urea functional groups in gelators 1315 was expected to be reinforced by electron-withdrawing substitution of the aromatic head group leading to more acidic NH groups and consequently stronger hydrogen bonding interactions, with improved gelation. However, the reverse was found and gel formation studies on gelators 14 and 15 showed that the presence of electron donating OCH3 could improve the gelation performances in two of the three selected solvents. We note that the same effect is seen in comparing 11 to 12, while with shorter chain lengths (5 vs 6) there is some evidence that the NO2 substituent improves gelation (Table 1). These observations indicate that there must be a balance of effects that influence the gelation behaviour, related to alkyl chain length, substituent electron donating or withdrawing ability, and perhaps other, less intuitive, substituent effects.
Thermo-mechanical and morphological characterisation of the gels
Studies were conducted to explore whether a simple correlation existed between the gelation performance of a compound and the thermo-mechanical characteristic of the resulting gel. The gels derived from 14 (NO2) and 15 (OCH3) in toluene were selected for more detailed studies.
The gel-sol transition temperatures (Tgel) were obtained b y d i f f e r e n t i a l s c a n n i n g c a l o r i m e t r y ( D S C ) m e a s u r e m e n t s . E a c h g e l s a m p l e ( H" 2 0 m g o f g e l s a t 2 0 m g m L 1 ) u n d e r w e n t a h e a t i n g - c o o l i n g - h e a t i n g c y c l e f r o m 3 0 t o 1 8 0 C a t a r a t e o f 1 0 C m i n 1 i n s e a l e d a l u m i n i u m p a n s . I n b o t h s a m p l e s , c h a r a c t e r i s t i c t h e r m a l e v e n t s w e r e o n l y p r e s e n t i n t h e f i r s t h e a t i n g r a m p . T h e i r T g e l w a s f o u n d t o b e 7 5 C f o r g e l 1 4 a n d 8 6 C f o r g e l 1 5 .
R h e o l o g i c a l t e s t s w e r e p e r f o r m e d w i t h b o t h g e l s s h o w i n g a s o l i d - l i k e b e h a v i o u r , w h e r e t h e s t o r a g e m o d u l u s ( G ' , H" 1 0 3 P a ) w a s s y s t e m a t i c a l l y l a r g e r t h a n t h e l o s s m o d u l u s ( G ' ' , H" 1 0 2 P a ) b y r o u g h l y o n e o r d e r o f m a g n i t u d e a n d p a r a l l e l t o e a c h o t h e r w i t h r e s p e c t t o t h e a n g u l a r f r e q u e n c y . T h e i r r i g i d b e h a v i o u r w a s f u r t h e r p r o v e d i n o s c i l l a t i o n s w e e p e x p e r i m e n t s , w h e r e t h e p h a s e a n g l e , t h a t m e a s u r e s t h e d e l a y b e t w e e n s t r e s s a n d s t r a i n , w a s f o u n d a l w a y s a r o u n d 1 0 ( a n i d e a l e l a s t i c s o l i d h a s = 0 ) . A d d i t i o n a l l y , t h e p h a s e a n g l e s h o w e d n o s i g n i f i c a n t v a r i a t i o n a c r o s s t h e f r e q u e n c y r a n g e i n v e s t i g a t e d , i n d i c a t i n g t h e a b i l i t y o f a l l g e l s t o w i t h s t and stresses below their yield stress value without showing signs of mechanical fatigue.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-9538032-0-1", "author" : [ { "dropping-particle" : "", "family" : "Barnes", "given" : "Howard A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "13.3.8", "container-title" : "The oscillatory response of real systems, A Handbook of Elementary Rheology", "edition" : "1st Ed.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "92-98", "publisher" : "The University of Wales Institute of Non-Newtonian Fluid Mechanics", "title" : "The oscillatory response of real systems", "type" : "chapter" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=7ff1c57a-ba97-424b-ae0f-59dac0a5bda2" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/C4RA15241G", "abstract" : "Six urea-based supramolecular gels have been obtained in situ by mixing either (R)-(-)-1-(1-naphthyl)ethyl isocyanate or (+/-)-1-(1-naphthyl)ethyl isocyanate with various amines. This allowed a comparative study on the effects of chirality on the response of the molecular gels to the presence of the neutral organophosphate guest dimethyl methylphosphonate (DMMP). The inversion test results show that the absence of enantiomeric purity causes marked instability of the gel network in the presence of the guest. DSC and rheology measurements reveal the promotion of a structural reinforcement of the gels when 0.01 mL of DMMP interacts with the enantiomerically pure systems. This effect was investigated by means of electrostatic potential surface calculations and 31P-{1H} NMR spectroscopy.", "author" : [ { "dropping-particle" : "", "family" : "Piana", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Facciotti", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pileio", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiscock", "given" : "Jennifer R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossom", "given" : "Wim", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Richard C D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gale", "given" : "Philip A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RSC Adv.", "id" : "ITEM-2", "issue" : "16", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "12287-12292", "publisher" : "The Royal Society of Chemistry", "title" : "Organophosphorus chemical warfare agent simulant DMMP promotes structural reinforcement of urea-based chiral supramolecular gels", "type" : "article-journal", "volume" : "5" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=54d1c4c5-3677-4ad3-a2a9-02e0945ad30a" ] } ], "mendeley" : { "formattedCitation" : "24,25", "plainTextFormattedCitation" : "24,25", "previouslyFormattedCitation" : "24,25" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }24,25 The oscillation stress sweep experiments demonstrated that the strength of the material was increasing from gel 14 to g e l 1 5 , a s c o n f i r m e d b y b o t h r e l a t i v e o r d e r a n d p o s i t i o n o f t h e c u r v e s . I t w a s n o t p o s s i b l e t o e x t r a p o l a t e t h e y i e l d s t r e s s v a l u e s a t = 4 5 s i n c e G ' a n d G ' ' d a t a s e t s n e v e r c r o s s e d e a c h o t h e r , a s t h e s t r u c t u r e b r o k e d o w n s u d d e n l y b e f o r e t h e f i n a l d a t a p oint could be collected.
Rheology measurements, in accordance with DSC outcomes, showed the existence of a correlation between the gelation performance and the thermo-mechanical characteristics of the gel materials. 4-Nitrophenyl urea 14, a gelator with higher MGC values and therefore poorer tendency to self-assemble, also resulted in a less stable network and consequently in a weaker material when compared to 4-methoxy phenyl urea derived gel 15.
Furthermore, environmental scanning electron microscopy (ESEM) was used to investigate morphological differences in dried gel samples, defined as xerogels, obtained from gels 14 and 15 in toluene. Two kinds of morphologies were observed in Fig. 2, possibly reflecting the head groups influence in the supramolecular packing of the corresponding gelators during the formation of the network. Interestingly, xerogel 15 presented a more fibrillar network, when compared to xerogel 14.
Fig. 2 ESEM images at 500x magnification for xerogels 14 and 15.
Molecular modelling
To help interpret the observed differences in gelation between 14 and 15, electronic-structure calculations were performed on both isolated molecules, as well as crystal structure prediction (CSP) calculations on both molecules. We applied CSP methods here to take advantage of the developments that have been made in this area over the past few yearsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0889311X.2010.517526", "ISSN" : "0889-311X", "author" : [ { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Crystallography Reviews", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "3-52", "title" : "Current approaches to predicting molecular organic crystal structures", "type" : "article-journal", "volume" : "17" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=d3f8c0b7-1f25-4482-a495-8e23477c9686" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "http://dx.doi.org/10.1016/j.ijpharm.2011.03.058", "ISSN" : "0378-5173", "abstract" : "The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed.", "author" : [ { "dropping-particle" : "V", "family" : "Kazantsev", "given" : "Andrei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamertzanis", "given" : "Panagiotis G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adjiman", "given" : "Claire S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelides", "given" : "Constantinos C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Sarah L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galek", "given" : "Peter T A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz-Cabeza", "given" : "Aurora J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Pharmaceutics", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "note" : "A priori Performance Predictions", "page" : "168-178", "title" : "Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction", "type" : "article-journal", "volume" : "418" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=093ef83b-75df-4d66-8fd6-6bc84e9c0661" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/anie.200704247", "ISSN" : "1521-3773", "author" : [ { "dropping-particle" : "", "family" : "Neumann", "given" : "Marcus A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leusen", "given" : "Frank J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kendrick", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Angewandte Chemie International Edition", "id" : "ITEM-3", "issue" : "13", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2427-2430", "publisher" : "WILEY-VCH Verlag", "title" : "A Major Advance in Crystal Structure Prediction", "type" : "article-journal", "volume" : "47" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=410d211a-030b-4a24-8841-90ff286b8dcc" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1021/ct500621v", "abstract" : "A key step in many approaches to crystal structure prediction (CSP) is the initial generation of large numbers of candidate crystal structures via the exploration of the lattice energy surface. By using a relatively simple lattice energy approximation, this global search step aims to identify, in a computationally tractable manner, a limited number of likely candidate structures for further refinement using more detailed models. This paper presents an effective and efficient approach to modeling the effects of molecular flexibility during this initial global search. Local approximate models (LAMs), constructed via quantum mechanical (QM) calculations, are used to model the conformational energy, molecular geometry, and atomic charge distributions as functions of a subset of the conformational degrees of freedom (e.g., flexible torsion angles). The effectiveness of the new algorithm is demonstrated via its application to the recently studied 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) molecule and to two molecules, \u03b2-d-glucose and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione, a Bristol Myers Squibb molecule referenced as BMS-488043. All three molecules present significant challenges due to their high degree of flexibility.", "author" : [ { "dropping-particle" : "", "family" : "Habgood", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugden", "given" : "Isaac J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Kazantsev", "given" : "Andrei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adjiman", "given" : "Claire S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelides", "given" : "Constantinos C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Chemical Theory and Computation", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1957-1969", "title" : "Efficient Handling of Molecular Flexibility in Ab Initio Generation of Crystal Structures", "type" : "article-journal", "volume" : "11" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=75ae26bf-5a65-406c-815e-90e619fa9598" ] } ], "mendeley" : { "formattedCitation" : "26\u201329", "plainTextFormattedCitation" : "26\u201329", "previouslyFormattedCitation" : "26\u201329" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }2629 in predicting the preferred solid-state assembly of organic molecules using a global search of the lattice energy surface. This global optimisation approach provides an unbiased assessment of molecular packing possibilities in a solid state environment, unlike other recent molecular modelling studies of gel structure based on assumed supramolecular arrangementsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/ja403345p", "ISSN" : "0002-7863", "author" : [ { "dropping-particle" : "", "family" : "Sun", "given" : "Zhifang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Zhengyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "He", "given" : "Yonghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Rujuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Liu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Minghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Yizeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Chemical Society", "id" : "ITEM-1", "issue" : "36", "issued" : { "date-parts" : [ [ "2013", "9", "11" ] ] }, "page" : "13379-13386", "title" : "Ferrocenoyl Phenylalanine: A New Strategy Toward Supramolecular Hydrogels with Multistimuli Responsive Properties", "type" : "article-journal", "volume" : "135" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=1c9ff432-3777-4f88-b70f-0a4e329dce2a" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/chem.201300642", "ISSN" : "09476539", "author" : [ { "dropping-particle" : "", "family" : "Vuji\u010di\u0107", "given" : "Nata\u0161a \u0160ijakovi\u0107", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glasovac", "given" : "Zoran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zweep", "given" : "Niek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esch", "given" : "Jan H.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinkovi\u0107", "given" : "Marijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Popovi\u0107", "given" : "Jasminka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "\u017dini\u0107", "given" : "Mladen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemistry - A European Journal", "id" : "ITEM-2", "issue" : "26", "issued" : { "date-parts" : [ [ "2013", "6", "24" ] ] }, "page" : "8558-8572", "title" : "Chiral Hexa- and Nonamethylene-Bridged Bis( L -Leu-oxalamide) Gelators: The First Oxalamide Gels Containing Aggregates with a Chiral Morphology", "type" : "article-journal", "volume" : "19" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=6c57c411-a3ff-4f60-b92f-518cf4707399" ] } ], "mendeley" : { "formattedCitation" : "30,31", "plainTextFormattedCitation" : "30,31", "previouslyFormattedCitation" : "30,31" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }30,31 conformational sampling of small molecular clustersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/jo200766u", "ISSN" : "0022-3263", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Masahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Toshiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mack", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Nagao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haino", "given" : "Takeharu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Organic Chemistry", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2011", "6", "17" ] ] }, "page" : "5082-5091", "title" : "Self-Assembly and Gelation Behavior of Tris(phenylisoxazolyl)benzenes", "type" : "article-journal", "volume" : "76" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=2501126f-5afb-46d2-b976-df586db90daa" ] } ], "mendeley" : { "formattedCitation" : "32", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "32" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }32, or dynamical simulations of pre-arranged fibre models.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/jp074420n", "ISSN" : "1520-6106", "author" : [ { "dropping-particle" : "", "family" : "Velichko", "given" : "Yuri S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stupp", "given" : "Samuel I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "la Cruz", "given" : "Monica Olvera", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Physical Chemistry B", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2008", "2" ] ] }, "page" : "2326-2334", "title" : "Molecular Simulation Study of Peptide Amphiphile Self-Assembly", "type" : "article-journal", "volume" : "112" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=32c6c244-ed87-46b6-bdf1-71e228a8addb" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1021/ja110966y", "ISSN" : "0002-7863", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "One-Sun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stupp", "given" : "Samuel I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schatz", "given" : "George C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Chemical Society", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "3", "16" ] ] }, "page" : "3677-3683", "title" : "Atomistic Molecular Dynamics Simulations of Peptide Amphiphile Self-Assembly into Cylindrical Nanofibers", "type" : "article-journal", "volume" : "133" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=ae4b69b8-a5d8-462b-adbb-8504cf08028d" ] } ], "mendeley" : { "formattedCitation" : "33,34", "plainTextFormattedCitation" : "33,34", "previouslyFormattedCitation" : "33,34" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }33,34
While CSP calculations have been applied to fairly challenging molecules,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4SC00095A", "abstract" : "In principle{,} the development of computational methods for structure and property prediction offers the potential for the in silico design of functional materials. Here{,} we evaluate the crystal energy landscapes of a series of porous organic cages{,} for which small changes in chemical structure lead to completely different crystal packing arrangements and{,} hence{,} porosity. The differences in crystal packing are not intuitively obvious from the molecular structure{,} and hence qualitative approaches to crystal engineering have limited scope for designing new materials. We find that the crystal structures and the resulting porosity of these molecular crystals can generally be predicted in silico{,} such that computational screening of similar compounds should be possible. The computational predictability of organic cage crystal packing is demonstrated by the subsequent discovery{,} during screening of crystallisation conditions{,} of the lowest energy predicted structure for one of the cages.", "author" : [ { "dropping-particle" : "", "family" : "Pyzer-Knapp", "given" : "Edward O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Hugh P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schiffmann", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jelfs", "given" : "Kim E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Samantha Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Little", "given" : "Marc A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Andrew I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem. Sci.", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2235-2245", "publisher" : "The Royal Society of Chemistry", "title" : "Predicted crystal energy landscapes of porous organic cages", "type" : "article-journal", "volume" : "5" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=ef49823e-f266-4fae-8fee-976cc8fa10f6" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "http://dx.doi.org/10.1016/j.ces.2014.08.058", "ISSN" : "0009-2509", "abstract" : "Abstract Organic molecules can crystallize in multiple structures or polymorphs, yielding crystals with very different physical and mechanical properties. The prediction of the polymorphs that may appear in nature is a challenge with great potential benefits for the development of new products and processes. A multistage crystal structure prediction (CSP) methodology is applied to axitinib, a pharmaceutical molecule with significant polymorphism arising from molecular flexibility. The {CSP} study is focused on those polymorphs with one molecule in the asymmetric unit. The approach successfully identifies all four known polymorphs within this class, as well as a large number of other low-energy structures. The important role of conformational flexibility is highlighted. The performance of the approach is discussed in terms of both the quality of the results and various algorithmic and computational aspects, and some key priorities for further work in this area are identified.", "author" : [ { "dropping-particle" : "", "family" : "Vasileiadis", "given" : "Manolis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelides", "given" : "Constantinos C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adjiman", "given" : "Claire S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Engineering Science", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "note" : "2013 Danckwerts Special Issue on Molecular Modelling in Chemical Engineering", "page" : "60-76", "title" : "Prediction of the crystal structures of axitinib, a polymorphic pharmaceutical molecule", "type" : "article-journal", "volume" : "121" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=4a288bd4-2c61-41ff-9e7d-e90fe3874787" ] } ], "mendeley" : { "formattedCitation" : "35,36", "plainTextFormattedCitation" : "35,36", "previouslyFormattedCitation" : "35,36" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }35,36 due to the size and possible conformational flexibility of these molecules, the extent to which their crystal packing possibilities could be sampled is limited. Moreover, CSP generates perfect crystalline arrangements of the molecules, which might not correspond to the packing that is present in gel fibres. Therefore, the realistic goal of this study was not to determine the packing of molecules in the gel fibres, but to understand the molecules preferred intermolecular arrangements, and the influence on solid-state packing of changing the substitution of the aromatic ring.
The initial motivation for investigating different aromatic substitutions stemmed from the potential ability of electron withdrawing or donating substituents to tune the acidity of the urea group. To investigate this inductive effect, single molecule density functional theory (DFT) calculations were performed using DMol3ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1063/1.1316015", "ISSN" : "00219606", "author" : [ { "dropping-particle" : "", "family" : "Delley", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Chemical Physics", "id" : "ITEM-1", "issue" : "18", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "7756", "title" : "From molecules to solids with the DMol[sup 3] approach", "type" : "article-journal", "volume" : "113" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=bbc9c59d-be6d-4d20-b2c9-970dfac9627c" ] } ], "mendeley" : { "formattedCitation" : "37", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "37" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }37 at the B3LYP/DNP level of theory to investigate the electrostatic potential around 14 and 15. These calculations revealed a slightly more positive electrostatic potential at the polar hydrogen atoms of the urea in 14 compared to 15, as shown in Fig. 3, and a more negative e l e c t r o s t a t i c p o t e n t i a l i n t h e p- e l e c t r o n r e g i o n o f t h e a r o m a t i c r i n g f o r 1 5 . T h e s e d i f f e r e n c e s r e f l e c t t h e e x p e c t e d i n f l u e n c e o f t h e e l e c t r o n w i t h d r a w i n g a n d d o n a t i n g s u b s t i t u e n t s . H o w e v e r , t h e m o r e c o n s p i c u o u s d i f f e r e n c e b e t w e e n t h e m o l e c u l e s w a s t h e i n t roduction of a region of negative charge at the NO2 substituent in 14. The oxygen atoms in the NO2 group of 14 are particularly accessible, so are positioned to easily compete with the urea oxygen as hydrogen bond acceptors for the protons of the urea group. Similarly, the oxygen of the OCH3 substituent in gelator 15 also introduced a region of negative charge, but one that was much less strong and was shielded to some extent by the steric bulk of the methyl. These details of the electrostatic potential are significant, as they could affect the disruption of the urea zipping, which was associated with good gelation properties.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/B926219A", "ISSN" : "0306-0012", "abstract" : "This tutorial review looks at the formation of low molecular weight gels from molecular principles using the well-explored supramolecular chemistry of ureas as an example. Synthesising lessons learned from classical urea inclusion chemistry, ureas in crystal engineering, ureas in self-assembly, urea functional groups in anion binding and sensing, and ureas as organocatalysts lead to the development and understanding of a new class of anion-tunable, urea-based soft materials. This review concludes with a look at emerging application areas for tunable gel-phase materials as controlled crystal growth media, both in templating metallic nanoparticles and in the growth and isolation of high quality crystals of molecular organic compounds, including polymorphic pharmaceuticals.", "author" : [ { "dropping-particle" : "", "family" : "Steed", "given" : "Jonathan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Society Reviews", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "3686-3699", "publisher" : "The Royal Society of Chemistry", "title" : "Anion-tuned supramolecular gels: a natural evolution from urea supramolecular chemistry", "type" : "article-journal", "volume" : "39" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=849d7b04-da98-41f9-958d-cbefeb52c1d4" ] } ], "mendeley" : { "formattedCitation" : "15", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "15" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }15
Fig. 3 Calculated molecular electrostatic potentials of 14 (a-c) and 15 (d-f). The potentials are plotted on the 0.02 a.u. electronic isodensity surface. The red patches of positive electrostatic potential in b) and e) correspond to the urea hydrogen atom positions. c) and f) show the view down the urea oxygen atom, highlighting its negative electrostatic potential.
In a study of the effects of anions on urea gelators, Steed has reported that only anions of sufficient hardness can disrupt this pattern.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C1SM06448G", "abstract" : "A series of chiral bis(urea) compounds based on oligomethylene spacers with S-phenylethyl end groups have been investigated as low molecular weight gelators. The series shows gelation of a variety of liquids and their structural{,} morphological and rheological properties are reported. The bis(urea) compounds also act as supramolecular hosts for anions such as chloride and acetate and the weakening of the gels by competitive anion complexation on this series of archetypical{,} low molecular weight gels is reported. Modification of gel properties using gel mixtures is also described and the gelation process studied using a fluorescent napthyl analogue.", "author" : [ { "dropping-particle" : "", "family" : "Lloyd", "given" : "Gareth O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piepenbrock", "given" : "Marc-Oliver M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foster", "given" : "Jonathan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Nigel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steed", "given" : "Jonathan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "204-216", "publisher" : "The Royal Society of Chemistry", "title" : "Anion tuning of chiral bis(urea) low molecular weight gels", "type" : "article-journal", "volume" : "8" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=fa14871a-df02-4fe3-977c-15c2f3db29ee" ] } ], "mendeley" : { "formattedCitation" : "38", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "38" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }38 In comparing 14 to 15, the increased acidity of the urea hydrogen atoms could enhance the formation of urea tapes in 14, while the presence of competing hydrogen bond acceptors might have disrupted their formation. The purpose of performing CSP calculations was to explore the balance of these competing effects and the overall influence of the aromatic substituents on the preferred arrangement of these molecules.
Putative crystal structures were generated using the Global Lattice Energy Explorer software,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C3FD00162H", "abstract" : "The ability of computational methods to predict the structures and energetics that determine the equilibrium of solid state mechanochemical reactions has been assessed. Two previously characterised base-catalysed metathesis reactions between aromatic disulfides are studied using crystal structure prediction methods and lattice energy calculations that combine molecular electronic structure methods with anisotropic atom-atom potentials. We find that lattice energy searches locate three of the six crystal structures as global minima on their respective crystal energy landscapes. The remaining structures are less successfully predicted{,} due to problems modelling relative conformational energies due to limitations of the density functional theory method for calculating intramolecular energies. Prediction of the overall reaction energies proves challenging for current methods{,} but the results show promise as a base on which to build more accurate and reliable approaches.", "author" : [ { "dropping-particle" : "", "family" : "Bygrave", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Case", "given" : "David H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Faraday Discuss.", "id" : "ITEM-1", "issue" : "0", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "41-57", "publisher" : "The Royal Society of Chemistry", "title" : "Is the equilibrium composition of mechanochemical reactions predictable using computational chemistry?", "type" : "article-journal", "volume" : "170" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=14960510-1d7c-4029-8d01-4ef5517a44bd" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Case", "given" : "David H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bygrave", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Under review. pdf in submission pack directory.", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Under review. A copy of the pdf is in the submission pack directory.", "type" : "article-journal" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=f7c9a172-5bc3-4769-bf17-002676e6ef6a" ] } ], "mendeley" : { "formattedCitation" : "39,40", "plainTextFormattedCitation" : "39,40", "previouslyFormattedCitation" : "39,40" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }39,40 performing quasi-random crystal structure generation, followed by lattice energy minimisation. An initial study was performed with rigid, gas phase molecular geometries, generating 5000 crystal structures in each of 16 common space groups for organic molecules, for both 14 and 15 (rigid searches were performed with two orientations of the OCH3 group on 15, which differed by only 1.2 kJ mol1). All crystal structures were lattice energy minimised using a force field model combining an empirically parameterised model of exchange-repulsion and dispersion interactions with an accurate atomic multipole model for intermolecular electrostatics.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C004164E", "abstract" : "Crystal structure prediction for organic molecules requires both the fast assessment of thousands to millions of crystal structures and the greatest possible accuracy in their relative energies. We describe a crystal lattice simulation program{,} DMACRYS{,} emphasizing the features that make it suitable for use in crystal structure prediction for pharmaceutical molecules using accurate anisotropic atom-atom model intermolecular potentials based on the theory of intermolecular forces. DMACRYS can optimize the lattice energy of a crystal{,} calculate the second derivative properties{,} and reduce the symmetry of the spacegroup to move away from a transition state. The calculated terahertz frequency k = 0 rigid-body lattice modes and elastic tensor can be used to estimate free energies. The program uses a distributed multipole electrostatic model (Qat{,} t = 00{,}...{,}44s) for the electrostatic fields{,} and can use anisotropic atom-atom repulsion models{,} damped isotropic dispersion up to R-10{,} as well as a range of empirically fitted isotropic exp-6 atom-atom models with different definitions of atomic types. A new feature is that an accurate model for the induction energy contribution to the lattice energy has been implemented that uses atomic anisotropic dipole polarizability models ([small alpha]at{,} t = (10{,}10)...(11c{,}11s)) to evaluate the changes in the molecular charge density induced by the electrostatic field within the crystal. It is demonstrated{,} using the four polymorphs of the pharmaceutical carbamazepine C15H12N2O{,} that whilst reproducing crystal structures is relatively easy{,} calculating the polymorphic energy differences to the accuracy of a few kJ mol-1 required for applications is very demanding of assumptions made in the modelling. Thus DMACRYS enables the comparison of both known and hypothetical crystal structures as an aid to the development of pharmaceuticals and other speciality organic materials{,} and provides a tool to develop the modelling of the intermolecular forces involved in molecular recognition processes.", "author" : [ { "dropping-particle" : "", "family" : "Price", "given" : "Sarah L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leslie", "given" : "Maurice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Gareth W A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Habgood", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Louise S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamertzanis", "given" : "Panagiotis G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Phys. Chem. Chem. Phys.", "id" : "ITEM-1", "issue" : "30", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "8478-8490", "publisher" : "The Royal Society of Chemistry", "title" : "Modelling organic crystal structures using distributed multipole and polarizability-based model intermolecular potentials", "type" : "article-journal", "volume" : "12" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=fd473620-8643-4776-aec4-6b79fed2a6f9" ] } ], "mendeley" : { "formattedCitation" : "41", "plainTextFormattedCitation" : "41", "previouslyFormattedCitation" : "41" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }41 This rigid molecule approach allowed a fairly rapid exploration of crystal packing phase space, due to the reduced dimensionality of the search space and requirement only to consider intermolecular interactions in assessing the relative stabilities of the predicted structures.
These initial calculations displayed a clear difference in the predicted crystal packing behaviours of gelators 14 and 15. The low energy predicted structures of gelator 15 displayed hydrogen bonding between urea groups, predominantly forming the one-dimensional urea chains or tapes (Fig. 4d, 4f) that were associated with gel fibre formation. The OCH3 did not participate in hydrogen bonding. In contrast, the low energy structures of 14 lacked the NHOurea hydrogen bonding linking urea into one-dimensional chains or tapes; the CSP results suggested that the urea tape formation was disrupted by the presence of the NO2 group, which preferentially acted as a hydrogen bond acceptor amongst the low energy predicted crystal structures (Fig. 4b).
To verify that these findings were not biased by the simplification of using rigid molecular geometries in the crystal structure search, further CSP calculations were performed with flexibility of the molecular geometry allowed during structure generation and lattice energy minimisation. These more demanding calculations provide the opportunity for molecules to explore packing arrangements that are inaccessible to the molecules in their gas phase geometries, as well as to optimise their hydrogen bonding networks, which can be very sensitive to small changes in molecular geometry. A further 5000 crystal structures were generated and minimised in each of the same 16 space groups for each molecule, with flexibility in the two dihedral angles around NC bonds connecting the urea to the aromatic ring and alkyl chain. Flexibility of the dihedral connecting the NO2 or OCH3 group to the aromatic ring was also included. Molecular distortion corresponding to up 22 kJ mol1 was allowed during the search, as this is the largest intramolecular strain seen in crystalline molecular geometries of small organic molecules.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c4sc01132e", "ISSN" : "2041-6520", "author" : [ { "dropping-particle" : "", "family" : "Thompson", "given" : "Hugh P. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Science", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "3173", "title" : "Which conformations make stable crystal structures? Mapping crystalline molecular geometries to the conformational energy landscape", "type" : "article-journal", "volume" : "5" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=2588d36c-6d76-4754-9b26-cac9ad9c3a72" ] } ], "mendeley" : { "formattedCitation" : "42", "plainTextFormattedCitation" : "42", "previouslyFormattedCitation" : "42" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }42
Unlike intermolecular interactions, atom-atom force fields to describe intramolecular energies lack the accuracy required for CSP. Modern methods combine atom-atom intermolecular models with a DFT description of intramolecular geometry and energy.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "http://dx.doi.org/10.1016/j.ijpharm.2011.03.058", "ISSN" : "0378-5173", "abstract" : "The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed.", "author" : [ { "dropping-particle" : "V", "family" : "Kazantsev", "given" : "Andrei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamertzanis", "given" : "Panagiotis G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adjiman", "given" : "Claire S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelides", "given" : "Constantinos C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Sarah L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galek", "given" : "Peter T A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz-Cabeza", "given" : "Aurora J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Pharmaceutics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "note" : "A priori Performance Predictions", "page" : "168-178", "title" : "Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction", "type" : "article-journal", "volume" : "418" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=093ef83b-75df-4d66-8fd6-6bc84e9c0661" ] } ], "mendeley" : { "formattedCitation" : "27", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "27" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }27 Here, we applied a newly developed method in which the intramolecular energies and atomic partial charges were modelled with a Gaussian process regression model fitted to DFT data.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Bygrave", "given" : "P.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Case", "given" : "David H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gee", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "In preparation", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "In preparation", "type" : "article-journal" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=ad436563-99b3-4693-b1c0-8982a912a951" ] } ], "mendeley" : { "formattedCitation" : "43", "plainTextFormattedCitation" : "43", "previouslyFormattedCitation" : "43" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }43 Details of the model, structure generation and energy minimisation are provided as supplementary material. All structures generated with the flexible search had their final energies calculated with the same anisotropic atom-atom force field intermolecular energy model used in the rigid structure search.
Fig. 4 Molecular packing in representative low energy predicted crystal structures of 14 (a, b, c) and 15 (d, e, f). a) and d) are the global minimum energy crystal structures that have been located for each molecule. Calculated lattice energies of each structure are shown. Hydrogen bonds are shown as dashed blue lines. hydrogen atoms on the alkyl chains are hidden in (f) for clarity.
These flexible-molecule calculations did not change the overall conclusions from the initial calculations: Hydrogen bonded urea tapes dominate the low energy structures of 15, while the low energy structures of 14 are dominated by urea hydrogen bonded to NO2. However, the details of these interactions were modified by giving the molecule freedom to distort from its ideal geometry. For 14, a slight reorientation of the alkyl chain allowed the alignment of both NO2 oxygen atoms with urea hydrogen atoms, forming a double hydrogen bond, as shown in Fig. 4a. This interaction was found in the overall lowest energy predicted structures of 14 and provided a significant stabilisation. The total energy of the best structure involving the double hydrogen bond (Fig. 4a) is 9 kJ mol1 more stable than the lowest energy structure involving only one NO2 oxygen in hydrogen bonding (Fig. 4b). The lowest energy predicted crystal structure of 14 that displayed the urea hydrogen bond tape motif was a further 13 kJ mol1 higher in energy (Fig. 4c), outside the energetic range that would be observable in small molecule crystal structures.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C5CE00045A", "ISSN" : "1466-8033", "abstract" : "A computational study of 1061 experimentally determined crystal structures of 508 polymorphic organic molecules has been performed with state-of-the-art lattice energy minimisation methods{,} using a hybrid method that combines density functional theory intramolecular energies with an anisotropic atom-atom intermolecular model. Rigid molecule lattice dynamical calculations have also been performed to estimate the vibrational contributions to lattice free energies. Distributions of the differences in lattice energy{,} free energy{,} zero point energy{,} entropy and heat capacity between polymorphs are presented. Polymorphic lattice energy differences are typically very small: over half of polymorph pairs are separated by less than 2 kJ mol-1 and lattice energy differences exceed 7.2 kJ mol-1 in only 5% of cases. Unsurprisingly{,} vibrational contributions to polymorph free energy differences at ambient conditions are dominated by entropy differences. The distribution of vibrational energy differences is narrower than lattice energy differences{,} rarely exceeding 2 kJ mol-1. However{,} these relatively small vibrational free energy contributions are large enough to cause a re-ranking of polymorph stability below{,} or at{,} room temperature in 9% of the polymorph pairs.", "author" : [ { "dropping-particle" : "", "family" : "Nyman", "given" : "Jonas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CrystEngComm", "id" : "ITEM-1", "issue" : "28", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "5154-5165", "publisher" : "The Royal Society of Chemistry", "title" : "Static and lattice vibrational energy differences between polymorphs", "type" : "article-journal", "volume" : "17" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=d8e642c4-47f2-457b-b985-d1e34513d79c" ] } ], "mendeley" : { "formattedCitation" : "44", "plainTextFormattedCitation" : "44", "previouslyFormattedCitation" : "44" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }44 This gives an indication of the strength of the ability of the oxygen atoms on the NO2 group to interfere with the urea-tape packing motif.
For gelator 15, the influence of molecular flexibility on the predictions was subtler; here, freedom of the molecule to distort from its gas phase geometry led to some low energy structures with planar urea tapes (Fig. 4e), whereas these interactions were twisted or buckled in the best structures generated with the rigid gas phase geometry, as per Fig. 4d, 4f. The difference in lattice energies of the most stable predicted structures of each (198.8 kJ mol1 for 14 vs. 176.7 kJ mol1 for 15) further highlighted the strength of the ureaO2N interaction. The calculated lattice energies of the lowest energy urea-tape structures of each molecule, as shown in Fig. 4c vs. Fig. 4d, were remarkably similar.
There are various types of interactions in these systems, including hydrogen bonding and van der Waals interactions, which can be maximised by stacking of the aromatic rings and aligning molecular tails. All of the low energy structures in the CSP were densely packed. It was seen, though, that in the systems of gelator 15 all of the types of interactions were associated within a pair of neighbouring molecules, i.e. they had a tendency to align tails, urea groups, and aromatic groups in series, a behaviour that is thought to be associated with the formation of a self-assembled fibrillar network (SAFIN) in gels.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/cr400195e", "ISSN" : "0009-2665", "author" : [ { "dropping-particle" : "", "family" : "Babu", "given" : "Sukumaran Santhosh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Praveen", "given" : "Vakayil K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajayaghosh", "given" : "Ayyappanpillai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Reviews", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014", "1", "8" ] ] }, "note" : "doi: 10.1021/cr400195e", "page" : "1973-2129", "publisher" : "American Chemical Society", "title" : "Functional \u03c0-Gelators and Their Applications", "type" : "article-journal", "volume" : "114" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=cc44a4a4-bae4-42aa-8c14-f56dadeb5215" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/B417081B", "abstract" : "In recent years there has been immense interest in studying gels derived from low molecular mass gelators (supramolecular{,} or simply molecular gels). The motivation for this is not only to understand the fundamental aggregate structures in the gels at different length scales{,} but also to explore their potential for futuristic technological applications. Gels have been made sensitive to external stimuli like light and chemical entities by incorporating a spectroscopically active or a receptor unit as part of the gelator molecule. This makes them suitable for applications such as sensing and actuating. The diversity of gel structural architectures has allowed them to be utilized as templates to prepare novel inorganic superstructures for possible applications in catalysis and separation. Gels derived from liquid crystals (anisotropy gels) that can act as dynamically functional materials have been prepared{,} for example{,} for (re-writable) information recording. Supramolecular gels can be important in controlled release applications{,} in oil recovery{,} for gelling cryogenic fuels etc. They can also serve as media for a range of applications. This tutorial review highlights some of the instructive work done by various groups to develop smart and functional gels{,} and covers a wide spectrum of scientific interest ranging from medicine to materials science.", "author" : [ { "dropping-particle" : "", "family" : "Sangeetha", "given" : "Neralagatta M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maitra", "given" : "Uday", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem. Soc. Rev.", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "821-836", "publisher" : "The Royal Society of Chemistry", "title" : "Supramolecular gels: Functions and uses", "type" : "article-journal", "volume" : "34" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=2925918c-8e61-4a72-b089-c1c7725c0338" ] } ], "mendeley" : { "formattedCitation" : "4,45", "plainTextFormattedCitation" : "4,45", "previouslyFormattedCitation" : "4,45" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }4,45 For gelator 14, there was instead a strong interaction between the urea and th e N O 2 g r o u p o f m o l e c u l e s , b u t t h e s e t w o m o l e c u l e s c o u l d n o t t h e n a l i g n t h e i r t a i l s a n d a r r a n g e a r o m a t i c g r o u p s i n t o - s t a c k ( F i g . 4 a , 4 b ) . T h e s e C S P r e s u l t s s u g g e s t e d t h a t , r a t h e r t h a n t h e a c i d i t y o f t h e u r e a g r o u p d e t e r m i n i n g t h e d i f f e r e n c e i n b e h a v i o u r of 14 and 15, it was such compromises between sources of strong interaction that may cause the differing observations in the gel formation experiments.
Powder X-ray diffraction
Semicrystalline structures attributed to the gel fibres were verified by the presence of diffractions peaks in PXRD patterns acquired on gel samples without the need to removing any amount of solvent.
Comparison between the simulated and observed diffraction patterns must take into account the expected discrepancies between the lattice parameters of modelled structures and packing in the gel fibres, which are usually a few percent in lattice parameters, as well as differences in reflection intensities caused by orientation of the gel fibres. Nevertheless, several of the predicted crystal structures for each molecule were identified as giving similar simulated diffraction patterns to those observed from the gels (Fig. 5). These comparisons support the conclusions from the structure prediction: for 15, those structures that give similar PXRD patterns all include the hydrogen bond urea tapes, while urea-nitro hydrogen bonding is present in all structures of 14 that give good agreement with the observed diffraction pattern. The structures that give good agreement with the experimental PXRD patterns include some of the lowest energy predicted structures of each molecule (Fig. 4a, 4e, 198.8 kJ mol1 for 14 and 176.8 kJ mol1 for 15).
Fig. 5. Powder X-ray diffraction patterns of the gels (a) 14 and (b) 15 in DMSO, compared to simulated diffraction patterns from low energy predicted structures that give similar diffraction patterns to the gels. The simulated patterns from the predicted structures are labelled by their calculated lattice energies. The simulated diffraction patterns of 14 and 15 with lattice energies of 198.8 and 173.8 kJ mol1 correspond to the predicted crystal structures reported in Fig. 4a, 4e, respectively. A larger set of comparisons is provided in the supporting information.
NMR chemical shielding calculations were performed on all of the predicted structures that gave good agreement with gel PXRD patterns, vide infra.
NMR spectroscopy
NMR spectroscopy enabled us to get further insight into the molecular level organisation of the gels. This technique has already proven its potential in characterising structure and dynamics of soft materials.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/B926785A", "abstract" : "HRMAS 1H NMR is reported for the first time as a useful technique to gain insight into the dynamic properties of aggregates present in supramolecular gels. The study of several low molecular weight gelators with this technique in toluene and acetonitrile is described.", "author" : [ { "dropping-particle" : "", "family" : "Iqbal", "given" : "Sajid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez-LLansola", "given" : "Francisco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escuder", "given" : "Beatriu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miravet", "given" : "Juan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verbruggen", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willem", "given" : "Rudolph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Soft Matter", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1875-1878", "publisher" : "The Royal Society of Chemistry", "title" : "HRMAS 1H NMR as a tool for the study of supramolecular gels", "type" : "article-journal", "volume" : "6" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=223c984e-91cb-4a17-a838-4964e53d91a9" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.progpolymsci.2011.04.002", "ISSN" : "00796700", "abstract" : "Hydrogels and organogels are semi-solid systems, in which a liquid phase is immobilized by a three-dimensional network composed of self-assembled, intertwined polymer/gelator fibers. Investigations pertaining to these systems have only picked up speed in the last few decades. Consequently, many burning questions regarding these systems, such as the specific molecular requirements guaranteeing gelation, still await definite answers. Nonetheless, the application of different hydrogels and organogels to various areas of interest, i.e., as drug delivery devices, has been quick to follow their discoveries. The use of {NMR} spectroscopy for the characterization of polymer hydrogels and organogels has recently seen enormous growth. The {NMR} measurements involving magic angle spinning (MAS) in the solid-state NMR, spin relaxation times, nuclear Overhauser enhancements (NOE), or multiple-quantum (MQ) spectroscopy, the pulse field gradient (PFG) technique and magnetic resonance imaging (MRI) allow obtaining the detailed information on morphology, molecular organization, specific interactions and internal mobility of constituents. This review aims at providing a global view and capabilities all of these {NMR} methods in comprehensive studies of hydrogels and organogels, with special emphasis on the interplay between the morphology and molecular mobility of constituents and the intermolecular interactions.", "author" : [ { "dropping-particle" : "", "family" : "Shapiro", "given" : "Yury E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Progress in Polymer Science", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "9" ] ] }, "page" : "1184-1253", "title" : "Structure and dynamics of hydrogels and organogels: An NMR spectroscopy approach", "type" : "article-journal", "volume" : "36" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=bc1282a3-e021-47df-a772-0ed02bda9102" ] } ], "mendeley" : { "formattedCitation" : "46,47", "plainTextFormattedCitation" : "46,47", "previouslyFormattedCitation" : "46,47" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }46,47 These multiphasic materials required both solution and solid-state NMR spectroscopy to probe mobile entities and rigid components of the gel network, respectively. NMR studies were conducted with gels prepared from dimethyl sulfoxide to avoid overlapping of aromatic peaks with solvent peaks from toluene and tetralin. NOESY solution-state NMR experiments provided information on spatial connectivity between molecular regions in aggregated states7. Cross-peaks in 2D 1H1H NOESY spectra of gels 14 and 15 displayed the same phase as the diagonal peaks, as shown in Fig. 6, indicative of negative NOE enhancements, which are characteristic of large molecules. Since these systems are exclusively formed of small gelator molecules (< 600 Da), these negative enhancements can be attributed to medium-large supramolecular aggregates, which are the building blocks required for gel formation. Therefore, NOESY experiments allowed probing interactions originating the gel network.
Table 2 Intermolecular distances calculated from initial rates of NOE build-up curves with mixing time, using the HcHd distance as reference.
r ()Pair of protonsGel 14Gel 15Hc / Hd (ref)2.492.47NHa / NHb2.852.50CH3 / Hc4.24n/aCH3 / Hd4.11n/aCH3 / NHa4.03n/aCH3 / NHb4.31n/aNHa / Hc3.74n/aNHa / Hd3.58n/aNHb / Hc3.16*NHb / Hd3.40**Pairs of protons for which cross-peaks were observed only at mixing times longer than 0.25 s, thus preventing accurate calculations of distances.
As shown in Fig. 6, cross-peaks between the CH3 protons of the alkyl chain and the aromatic and urea ones were identified in gel 14, whereas they were not detected for gel 15. The presence of such cross-peaks in gel 14 revealed close proximity between the end of the aliphatic chain, the benzene ring and the urea moiety (Table 2), belonging either to the same or to surrounding molecules. Such an arrangement was suggested by the CSP calculations, whose results showed that the urea HO2N interaction leads to interdigitation of the aliphatic chains, as shown in Fig. 4a, 4b, which places the end of the chain near to the aromatic rings of neighbouring molecules. Furthermore, intermolecular cross-peaks between distant NHa and Hc or Hd (Fig. 6) suggested proximity of the aromatic ring to another molecule with a different orientation. Conversely, the absence of cross-peaks between the alkylic CH3 protons, the aromatic, the urea and the OCH3 sites in gel 15 suggested a well-aligned network in which the long aliphatic chains are positioned separately from aromatic and urea groups. In addition, the absence of cross-peaks between NHa and Hc or Hd (Fig. 6) was also in agreement with the predicted well defined stacking of the aromatic rings in the 3D network of gel 15.
1H13C CP/MAS NMR experimentsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/cr000060n", "ISSN" : "0009-2665", "author" : [ { "dropping-particle" : "", "family" : "Kolodziejski", "given" : "Waclaw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klinowski", "given" : "Jacek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Reviews", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "note" : "PMID: 11890752", "page" : "613-628", "title" : "Kinetics of Cross-Polarization in Solid-State NMR: A Guide for Chemists", "type" : "article-journal", "volume" : "102" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=d61e6f98-b661-40a7-a6ea-29cdf0f6044e" ] } ], "mendeley" : { "formattedCitation" : "48", "plainTextFormattedCitation" : "48", "previouslyFormattedCitation" : "48" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }48 can probe rigid components of the gel samples and were therefore used to study the molecular packing of the gel fibres. Despite the presence of high contents of solvent which was expected to lead to an increased mobility and a reduced efficiency of polarisation transfer, we were able to acquire 1H13C CP/MAS NMR spectra of gels 14 and 15. The detection of peaks in 1H13C CP/MAS NMR spectra of these gels was indicative of a rigid 3D fibrous network, with densely packed molecules as predicted by molecular modelling studies. To the best of our knowledge, this is the first example of supramolecular gels in which 1H13C CP/MAS NMR peaks were detectable without any physical modification of the gel samples, i.e. removing any amount of the solvent or lowering the temperature.49
For gels 14 and 15, aliphatic carbons appeared as sharp resonances, while low intensity peaks were observed for the aromatic and carbonyl carbons (and OCH3 carbon in gel 15) in spectra acquired at 25 C and 1 kHz MAS rate, as shown in Fig. 7a (the assignment is provided separately). The presence of sharp peaks is in agreement with the semicrystalline gel fibres identified in PXRD experiments. Lowering the temperature to 15, 10, 5 and 0 C enabled us to record 1H13C CP/MAS NMR spectra at higher MAS rates, as shown in Fig. 7b-7g. This led to significant narrowing of the aromatic and carbonyl carbons (and OCH3 carbon in gel 15), with spinning sidebands present in accordance with the specific MAS rate. No significant differences were observed for the chemical shift values in the spectra acquired at lower temperatures.
The 1H13C CP/MAS NMR spectrum of frozen gel 14 acquired at an MAS rate of 8 kHz (Fig. 7g) presented a single peak per carbon, indicative of one magnetic environment for each carbon site. Peaks at 125.7 and 117.2 ppm resulted from overlapped resonances of carbons C2 and C6, and C3 and C5, respectively (Fig. 8), as predicted by solid-state DFT calculations. The variation of chemical shift values between the reference solid powder 14 (Fig. 7h) and the resulting gel suggested the molecular organisation of the gel fibres was different from the reference solid powder.
In contrast to gel 14, frozen gel 15 acquired at an MAS rate of 8 kHz (Fig. 7g) showed several peaks per carbon in the aromatic region, indicating the same carbon can experience different magnetic environments in different molecules. These results suggested the presence of multiple symmetrically independent gel molecules in the structure. Structures with multiple independent molecules (Z` > 1) are not uncommon in molecular crystals and it is not surprising that this phenomenon carries over to gel fibre packing.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/cr500564z", "ISSN" : "0009-2665", "author" : [ { "dropping-particle" : "", "family" : "Steed", "given" : "Kirsty M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steed", "given" : "Jonathan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Reviews", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "4", "22" ] ] }, "note" : "PMID: 25675105", "page" : "2895-2933", "title" : "Packing Problems: High Z \u2032 Crystal Structures and Their Relationship to Cocrystals, Inclusion Compounds, and Polymorphism", "type" : "article-journal", "volume" : "115" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=272bb498-a436-4e2d-9e10-b3c522feb64a" ] } ], "mendeley" : { "formattedCitation" : "51", "plainTextFormattedCitation" : "51", "previouslyFormattedCitation" : "51" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }52 This observation reflects the symmetry of molecular packing and does not imply a less organised structure. However, this finding does mean that the packing in the gel 15 fibres cannot be perfectly described by any one of the predicted crystal structures, since the molecular modelling studies were conducted considering only one molecule in the asymmetric unit (Z` = 1). Furthermore, the similarity in chemical shift values of the reference solid powder 15 (Fig. 7h) and the resulting gel pointed towards a self-assembled network with a 3D organisation similar to that of the crystalline powder.
Fig. 6 2D 1H1H NOESY spectra of gels 14 and 15 (60 mg mL1 in DMSO-d6) were acquired at 25 C with a mixing time of 0.5 s using a 800.23 MHz spectrometer. Relevant cross-peaks have the corresponding spatial connectivity assigned (coloured lines). The cross-peaks observed between the CH2 and the aromatic protons in gel 15 do not contain structural information, as they result from indirect NOE enhancements, only observable at long mixing times.
Fig. 7 1H13C CP/MAS NMR spectra of gel samples (60 mg mL1 in DMSO-d6) acquired at 25 C and 1 kHz MAS rate (a), froz e n g e l s a m p l e s a c q u i r e d a t 1 5 C ( b ) , 1 0 C ( c ) a n d 5 C ( d ) a n d 1 k H z M A S r a t e , f r o z e n g e l s a m p l e s a c q u i r e d a t 0 C a n d 1 k H z ( e ) , 4 k H z ( f ) a n d 8 k H z ( g ) M A S r a t e s , a n d r e f e r e n c e s o l i d p o w d e r s a c q u i r e d a t 2 5 C a n d 1 0 k H z M A S r a t e ( h ) f o r 1 4 a n d 1 5 . L o w - r e s o l u t i o n a r o m a t i c p e a k s a r e h i g h l i g h t e d w i t h t r i a n g l e s ( ) a n d s p i n n i n g s i d e b a n d s w i t h a s t e r i s k s ( * ) .
F i g . 8 A r o m a t i c c a r b o n l a b e l s f o r g e l a t o r 1 4 .
F o r c o m p a r i s o n , N M R c h e m i c a l s h i e l d i n g c a l c u l a t i o n s w e r e p e r f o r m e d f o r t h e p r e d i c t e d c r y s t a l s t r u c t u r e s of gelators 14 and 15 and gave reasonable agreement with the gel X-ray diffraction pattern (Fig. 5), using DFT calculations (with the PBE functional and a plane wave basis set) and the GIPAWADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1103/PhysRevB.63.245101", "ISSN" : "0163-1829", "author" : [ { "dropping-particle" : "", "family" : "Pickard", "given" : "Chris J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauri", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physical Review B", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2001", "5", "10" ] ] }, "page" : "245101", "title" : "All-electron magnetic response with pseudopotentials: NMR chemical shifts", "type" : "article-journal", "volume" : "63" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=95731044-1f87-4e47-8754-627a3134567e" ] } ], "mendeley" : { "formattedCitation" : "49", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "49" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }50 methodology. Despite the similarities in intermolecular interactions, we found a reasonable variation in predicted chemical shifts from the selected structures (see supporting information). Amongst these structures, the simulated 13C chemical shifts for the lowest energy predicted structures (198.8 kJ mol1 for 14, reported in Fig. 4a, and 176.8 kJ mol1 for 15, reported in Fig. 4e) were found to be in best agreement with the 13C chemical shift values observed for gel fibres (Fig. 9), with RMSD (predicted observed) of 1.8 ppm for 14 and 1.4 ppm for 15. These deviations are as low as those seen in comparing observed 13C chemical shifts with those predicted from known single crystal structures of small organic molecules.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c3cp41095a", "ISSN" : "1463-9076", "abstract" : "A protocol for the ab initio crystal structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy{,} crystal structure prediction{,} and DFT chemical shift calculations was evaluated to determine the crystal structures of four small drug molecules: cocaine{,} flutamide{,} flufenamic acid{,} and theophylline. For cocaine{,} flutamide and flufenamic acid{,} we find that the assigned 1H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation (rmsd) between experimentally determined and calculated chemical shifts. In most cases unassigned shifts could not be used to determine the structures. This method requires no prior knowledge of the crystal structure{,} and was used to determine the correct crystal structure to within an atomic rmsd of less than 0.12 A with respect to the known reference structure. For theophylline{,} the NMR spectra are too simple to allow for unambiguous structure selection.", "author" : [ { "dropping-particle" : "", "family" : "Baias", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Widdifield", "given" : "Cory M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumez", "given" : "Jean-Nicolas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Hugh P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Timothy G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salager", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassil", "given" : "Sirena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stein", "given" : "Robin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lesage", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Graeme M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emsley", "given" : "Lyndon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physical Chemistry Chemical Physics", "id" : "ITEM-1", "issue" : "21", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "8069", "publisher" : "The Royal Society of Chemistry", "title" : "Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy", "type" : "article-journal", "volume" : "15" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=06b4e709-7b80-412f-b40d-01a28ee79f62" ] } ], "mendeley" : { "formattedCitation" : "50", "plainTextFormattedCitation" : "50", "previouslyFormattedCitation" : "50" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }50 These results strongly support the relevance of the predicted structures in interpreting the properties of the two gelators.
Fig. 9 Experimental 13C chemical shift values for frozen gels 14 and 15 acquired at 0 C and MAS rate of 8 kHz vs. calculated values for the predicted structures that give best agreement with both NMR and PXRD from the gel. Calculated isotropic chemical shieldings were converted to chemical shifts by matching the calculated and observed chemical shift of the CH3 carbon in gel. The structures for gelators 14 and 15 correspond to those reported in Fig. 4a, 4e, respectively.
The increased resolution obtained for the aromatic and carbonyl carbons (and OCH3 carbon in gel 15) upon spinning at higher MAS rates, with no significant changes for the aliphatic carbons, strongly indicated that chemical shift anisotropy is considerable for the aromatic and carbonyl carbons (and OCH3 carbon in gel 15), even in the gel state. The solid-state DFT calculations of NMR properties performed for the low energy predicted crystal structures confirmed that the anisotropy of the shielding tensors for the aromatic and carbonyl carbon atoms was much larger (in the range from 108 to 192 ppm) than for the aliphatic carbons (in the range from 19 to 43 ppm) for both gelators, supporting the previous conclusions. The OCH3 carbon in gel 15 was narrower than the aromatic carbons, but the peak sharpened as a result of spinning faster, in agreement with the DFT calculated intermediate anisotropy of the shielding tensor (ca. 70 ppm). Hence, the significantly broadened peaks detected for aromatic and carbonyl carbons at low MAS rates in 1H13C CP/MAS NMR spectra of gels 14 and 15 were most likely due to the high values of chemical shift anisotropy for these carbon sites.
Overall, the combination of calculation, diffraction and NMR studies provides valuable insight into the molecular level organisation, offering likely motifs of intermolecular packing and local structure in the gels.
Conclusions
The aim of this work was to study the influence of the electron-withdrawing (NO2) and electron-donating (OCH3) head substituents on the gelation performances of urea gelators. The thermo-mechanical characterisation of gels 14 (20 mg mL1) and 15 (5 mg mL1) confirmed the latter to be a stronger material, expressing higher Tgel and more solid-like rheological behaviour. The results of the crystal structure prediction calculations suggested that, rather than changes in the acidity of the urea group, the differences observed in their gelation performance is due to the presence of strong competing interactions between the NO2 head substituent and the urea. The computational studies of ideal crystals quantified these interactions, and we therefore suggest that the availability of substituent groups to form competing interactions must be considered in any programme of rationally designed self-assembling systems as gels. The crystalline arrangements produced by the modelling studies and their molecular contacts detected by NOESY solution-state NMR experiments showed that gelator 15 has a tendency to align tails, urea groups, and aromatic rings in series. Conversely, such well stacked supramolecular assemblies were not observed in gelator 14, due to the perturbing influence of the NO2 group on the formation of the urea tape motif. These materials were proven to be rigid by 1H13C CP/MAS solid-state NMR studies and therefore some insight into preferred molecular arrangements was gained, particularly through comparison with simulated chemical shifts of the predicted structures. Despite the limitations of molecular modelling studies of gels, when validated by solid-state NMR experiments, these have a great potential in unravelling structure of supramolecular gels.
Acknowledgements
FP, PAG and RCDB thank the A-I Chem Channel project, an European INTERREG IV A France (Channel) England Cross border cooperation programme, co-financed by ERDF. FP thanks Dr A. I. Pop for practical advice in the synthesis of some of the molecules. PAG and RCDB thank EPSRC EP/K039466/1 (Core Capability for Chemistry Research in Southampton). PAG thanks the Royal Society and the Wolfson Foundation for a Research Merit Award. DHC and GMD thank the European Research Council for funding under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 307358 (ERC-StG-2012-ANGLE). We acknowledge the use of the IRIDIS High Performance Computing Facility at the University of Southampton for CSP calculations, and via our membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202), the NMR modelling work used the ARCHER UK National Supercomputing Service. SMR thanks UEA for a postgraduate studentship.
Notes and references
These authors contributed equally.
Authors address:
a Chemistry, University of Southampton, Southampton, SO17 1BJ, UK
b School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
Electronic Supplementary Information (ESI) available: synthesis of the gelators, results of gelation studies, DSC, rheology, ESEM, CSP and NMR calculations, PXRD and NMR spectroscopy. See DOI:10.1039/b000000x/ Data from this paper has been available online at: DOI: 10.5258/SOTON/382352.
ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. N. Zweep and J. H. van Esch, in The Design of Molecular Gelators, Functional Molecular Gels - RSC Soft Matter Series, eds. B. Escuder and J. F. Miravet, The Royal Society of Chemistry, 2014, pp. 126.
2. P. Terech and R. G. Weiss, Chem. Rev., 1997, 97, 31333160.
3. J. H. van Esch, Langmuir, 2009, 25, 83928394.
4. N. M. Sangeetha and U. Maitra, Chem. Soc. Rev., 2005, 34, 821836.
5. D. M. Zurcher and A. J. McNeil, J. Org. Chem., 2015, 80, 24732478.
6. R. G. Weiss, J. Am. Chem. Soc., 2014, 136, 75197530.
7. F. S. Schoonbeek, J. H. van Esch, R. Hulst, R. M. Kellogg, and B. L. Feringa, Chem. - A Eur. J., 2000, 6, 26332643.
8. N. A. Dudukovic and C. F. Zukoski, Soft Matter, 2014, 10, 78497856.
9. H. Sato, E. Nogami, T. Yajima, and A. Yamagishi, RSC Adv., 2014, 4, 16591665.
10. K. L. Morris, L. Chen, A. Rodger, D. J. Adams, and L. C. Serpell, Soft Matter, 2015, 11, 11741181.
11. K. Hanabusa, K. Shimura, K. Hirose, M. Kimura, and H. Shirai, Chem. Lett., 1996, 25, 885886.
12. J. van Esch, R. M. Kellogg, and B. L. Feringa, Tetrahedron Lett., 1997, 38, 281284.
13. J. van Esch, S. De Feyter, R. M. Kellogg, F. De Schryver, and B. L. Feringa, Chem. - A Eur. J., 1997, 3, 12381243.
14. J. H. van Esch, F. Schoonbeek, M. de Loos, H. Kooijman, A. L. Spek, R. M. Kellogg, and B. L. Feringa, Chem. - A Eur. J., 1999, 5, 937950.
15. J. W. Steed, Chem. Soc. Rev., 2010, 39, 36863699.
16. D. J. Adams, K. Morris, L. Chen, L. C. Serpell, J. Bacsa, and G. M. Day, Soft Matter, 2010, 6, 41444156.
17. K. M. Anderson, G. M. Day, M. J. Paterson, P. Byrne, N. Clarke, and J. W. Steed, Angew. Chemie Int. Ed., 2008, 47, 10581062.
18. B. Escuder, S. Mart, and J. F. Miravet, Langmuir, 2005, 21, 67766787.
19. W. Edwards, C. A. Lagadec, and D. K. Smith, Soft Matter, 2011, 7, 110117.
20. Y. Lan, M. G. Corradini, R. G. Weiss, S. R. Raghavan, and M. A. Rogers, Chem. Soc. Rev., 2015, 44, 60356058.
21. K. K. Diehn, H. Oh, R. Hashemipour, R. G. Weiss, and S. R. Raghavan, Soft Matter, 2014, 10, 26322640.
22. C. A. Hunter, Angew. Chemie Int. Ed., 2004, 43, 53105324.
23. D. J. Abdallah and R. G. Weiss, Langmuir, 2000, 16, 352355.
24. H. A. Barnes, in The oscillatory response of real systems, A Handbook of Elementary Rheology, The University of Wales Institute of Non-Newtonian Fluid Mechanics, 1st Ed., 2000, pp. 9298.
25. F. Piana, M. Facciotti, G. Pileio, J. R. Hiscock, W. Van Rossom, R. C. D. Brown, and P. A. Gale, RSC Adv., 2015, 5, 1228712292.
26. G. M. Day, Crystallogr. Rev., 2011, 17, 352.
27. A. V Kazantsev, P. G. Karamertzanis, C. S. Adjiman, C. C. Pantelides, S. L. Price, P. T. A. Galek, G. M. Day, and A. J. Cruz-Cabeza, Int. J. Pharm., 2011, 418, 168178.
28. M. A. Neumann, F. J. J. Leusen, and J. Kendrick, Angew. Chemie Int. Ed., 2008, 47, 24272430.
29. M. Habgood, I. J. Sugden, A. V Kazantsev, C. S. Adjiman, and C. C. Pantelides, J. Chem. Theory Com p u t . , 2 0 1 5 , 1 1 , 1 9 5 7 1 9 6 9 .
3 0 . Z . S u n , Z . L i , Y . H e , R . S h e n , L . D e n g , M . Y a n g , Y . L i a n g , a n d Y . Z h a n g , J . A m . C h e m . S o c . , 2 0 1 3 , 1 3 5 , 1 3 3 7 9 1 3 3 8 6 .
3 1 . N . `. V u j i
i , Z . G l a s o v a c , N . Z w e e p , J . H . v a n E s c h , M . V i n k o v i , J . P o p o v i , a n d M . }i n i , C h e m . - A E # r ~
yiyZiJy; ho hs OJ QJ mH sH ho hM H*OJ QJ mH sH ho h
OJ QJ mH sH ho h/ H*OJ QJ mH sH ho h_Wu OJ QJ mH sH ho h OJ QJ mH sH ho h, OJ QJ mH sH ho ho OJ QJ mH sH ho h, mH sH ho hzS 5CJ OJ QJ aJ ho hAz 5CJ OJ QJ aJ ho h, CJ OJ QJ aJ ho h, 5CJ OJ QJ aJ # ? Z r % c J ߶ $ gd8 gd8 gdz` gd^ gdxP
+ @&