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Fluoride-selective binding in a new deep cavity calix[4]pyrrole: experiment and theory

Fluoride-selective binding in a new deep cavity calix[4]pyrrole: experiment and theory
Fluoride-selective binding in a new deep cavity calix[4]pyrrole: experiment and theory
A new "super-extended cavity" tetraacetylcalix[4]pyrrole derivative was synthesized and characterized, and X-ray crystal structures of complexes bound to fluoride and acetonitrile were obtained. The binding behavior of this receptor was investigated by NMR titration, and the complex was found to exclusively bind fluoride ions in DMSO-d6. This unusual binding behavior was investigated by Monte Carlo free energy perturbation simulations and Poisson calculations, and the ion specificity was seen to result from the favorable electrostatic interactions that the fluoride gains by sitting lower in the phenolic cavity of the receptor. The effect of water present in the DMSO on the calculated free energies of binding was also investigated. Owing to the use of a saturated ion solution, the effect of contaminating water is small in this case; however, it has the potential to be very significant at lower ion concentrations. Finally, the adaptive umbrella WHAM protocol was investigated and optimized for use in binding free energy calculations, and its efficiency was compared to that of the free energy perturbation calculations; adaptive umbrella WHAM was found to be approximately two times more efficient. In addition, structural evidence demonstrates that the protocol explores a wider conformational range than free energy perturbation and should therefore be the method of choice. This paper represents the first complete application of this methodology to "alchemical" changes.
free-energy calculations, monte-carlo simulations, anion complexation, electrostatics, calixpyrroles
0002-7863
8644-8652
Woods, Christopher J.
54c21a03-755f-4977-aa2c-72c1b073e734
Camiolo, Salvatore
4ea1c6a7-c0c9-48a0-8998-66a61de7d4d0
Light, Mark E.
cf57314e-6856-491b-a8d2-2dffc452e161
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Hursthouse, Michael B.
57a2ddf9-b1b3-4f38-bfe9-ef2f526388da
King, Michael A.
60520a12-4a45-435b-98bb-420eff76ab34
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Woods, Christopher J.
54c21a03-755f-4977-aa2c-72c1b073e734
Camiolo, Salvatore
4ea1c6a7-c0c9-48a0-8998-66a61de7d4d0
Light, Mark E.
cf57314e-6856-491b-a8d2-2dffc452e161
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Hursthouse, Michael B.
57a2ddf9-b1b3-4f38-bfe9-ef2f526388da
King, Michael A.
60520a12-4a45-435b-98bb-420eff76ab34
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5

Woods, Christopher J., Camiolo, Salvatore, Light, Mark E., Coles, Simon J., Hursthouse, Michael B., King, Michael A., Gale, Philip A. and Essex, Jonathan W. (2002) Fluoride-selective binding in a new deep cavity calix[4]pyrrole: experiment and theory. Journal of the American Chemical Society, 124 (29), 8644-8652. (doi:10.1021/ja025572t).

Record type: Article

Abstract

A new "super-extended cavity" tetraacetylcalix[4]pyrrole derivative was synthesized and characterized, and X-ray crystal structures of complexes bound to fluoride and acetonitrile were obtained. The binding behavior of this receptor was investigated by NMR titration, and the complex was found to exclusively bind fluoride ions in DMSO-d6. This unusual binding behavior was investigated by Monte Carlo free energy perturbation simulations and Poisson calculations, and the ion specificity was seen to result from the favorable electrostatic interactions that the fluoride gains by sitting lower in the phenolic cavity of the receptor. The effect of water present in the DMSO on the calculated free energies of binding was also investigated. Owing to the use of a saturated ion solution, the effect of contaminating water is small in this case; however, it has the potential to be very significant at lower ion concentrations. Finally, the adaptive umbrella WHAM protocol was investigated and optimized for use in binding free energy calculations, and its efficiency was compared to that of the free energy perturbation calculations; adaptive umbrella WHAM was found to be approximately two times more efficient. In addition, structural evidence demonstrates that the protocol explores a wider conformational range than free energy perturbation and should therefore be the method of choice. This paper represents the first complete application of this methodology to "alchemical" changes.

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Published date: 24 July 2002
Keywords: free-energy calculations, monte-carlo simulations, anion complexation, electrostatics, calixpyrroles

Identifiers

Local EPrints ID: 19872
URI: http://eprints.soton.ac.uk/id/eprint/19872
ISSN: 0002-7863
PURE UUID: 28c5bd1a-4708-4e8a-b615-e48e4eb3c7fa
ORCID for Mark E. Light: ORCID iD orcid.org/0000-0002-0585-0843
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272
ORCID for Philip A. Gale: ORCID iD orcid.org/0000-0001-9751-4910
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

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Date deposited: 22 Feb 2006
Last modified: 09 Jan 2022 03:03

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Contributors

Author: Christopher J. Woods
Author: Salvatore Camiolo
Author: Mark E. Light ORCID iD
Author: Simon J. Coles ORCID iD
Author: Michael A. King
Author: Philip A. Gale ORCID iD

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