Biological and structural studies of phosphonium ‘masked thiolate’ compounds
Biological and structural studies of phosphonium ‘masked thiolate’ compounds
The ability of phosphonium cations to act as intracellular transport vectors is well-established. Phosphonioalkylthiosulfate zwitterions, and w-thioacetylalkylphosphonium salts, which act as 'masked thiolate' ligands, are useful precursors for the formation of phosphonium-functionalised gold nanoparticles, enabling the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this study we have completed cytotoxicity studies of w-thioacetylpropylphosphonium salts derived from triphenylphosphine and tri(4-fluorophenyl)phosphine, which show that the compounds are only toxic towards PC3 prostate cancer cells at high concentrations and at prolonged incubation periods and display IC50 values of 67 ?M and 252 ?M respectively, significantly higher than those of other phosphonium salts. MALDI-TOF-MS has been used to investigate the uptake of the compounds by PC3 cells and to quantify detectable levels of the compounds inside the cells. The structures of w-thioacetylpropyl(tri-4-fluorophenyl) phosphonium bromide and the corresponding tri(4-fluorophenyl)phosphonio-propylthiosulfate zwitterion have been investigated by single crystal X-ray crystallography. The results show that molecules of the zwitterion are held together through an extensive array of electrostatic and non-covalent interactions. The unit cell of w-thioacetylpropyl(tri-4-fluorophenyl)phosphonium bromide contains eight cations together with eight bromide anions and two waters of crystallisation, all held together through a complex network of hydrogen bonds. The differences in the molecular packing of the two compounds may account for the lower solubility of the zwitterion in aqueous solutions, compared with that of the phosphonium salt.
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Chen, Yu-Su
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Allen, David W.
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Tizzard, Graham
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Pitak, Mateusz
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Coles, Simon
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Cross, Neil A.
71a10a02-6a23-444a-85b5-6033d0ed4e0a
Bricklebank, Neil
6e082c98-a747-4690-bb37-f05f24d621f5
Chen, Yu-Su
3840b827-cc48-49a4-b038-e7417493c460
Allen, David W.
4cbcd21b-4bb9-40e8-baa9-27b1b3e5a7b2
Tizzard, Graham
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Pitak, Mateusz
eeb6a00f-2291-4376-830f-d30dfd607ed1
Coles, Simon
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Cross, Neil A.
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Bricklebank, Neil
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Chen, Yu-Su, Allen, David W., Tizzard, Graham, Pitak, Mateusz, Coles, Simon, Cross, Neil A. and Bricklebank, Neil
(2016)
Biological and structural studies of phosphonium ‘masked thiolate’ compounds.
European Journal of Medicinal Chemistry, .
(doi:10.1016/j.ejmech.2016.08.025).
Abstract
The ability of phosphonium cations to act as intracellular transport vectors is well-established. Phosphonioalkylthiosulfate zwitterions, and w-thioacetylalkylphosphonium salts, which act as 'masked thiolate' ligands, are useful precursors for the formation of phosphonium-functionalised gold nanoparticles, enabling the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this study we have completed cytotoxicity studies of w-thioacetylpropylphosphonium salts derived from triphenylphosphine and tri(4-fluorophenyl)phosphine, which show that the compounds are only toxic towards PC3 prostate cancer cells at high concentrations and at prolonged incubation periods and display IC50 values of 67 ?M and 252 ?M respectively, significantly higher than those of other phosphonium salts. MALDI-TOF-MS has been used to investigate the uptake of the compounds by PC3 cells and to quantify detectable levels of the compounds inside the cells. The structures of w-thioacetylpropyl(tri-4-fluorophenyl) phosphonium bromide and the corresponding tri(4-fluorophenyl)phosphonio-propylthiosulfate zwitterion have been investigated by single crystal X-ray crystallography. The results show that molecules of the zwitterion are held together through an extensive array of electrostatic and non-covalent interactions. The unit cell of w-thioacetylpropyl(tri-4-fluorophenyl)phosphonium bromide contains eight cations together with eight bromide anions and two waters of crystallisation, all held together through a complex network of hydrogen bonds. The differences in the molecular packing of the two compounds may account for the lower solubility of the zwitterion in aqueous solutions, compared with that of the phosphonium salt.
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More information
Accepted/In Press date: 12 August 2016
e-pub ahead of print date: 18 August 2016
Organisations:
Organic Chemistry: SCF
Identifiers
Local EPrints ID: 402139
URI: http://eprints.soton.ac.uk/id/eprint/402139
ISSN: 0223-5234
PURE UUID: a62ef200-4109-464f-8a0c-2c020dbafb70
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Date deposited: 01 Nov 2016 17:13
Last modified: 16 Mar 2024 03:05
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Contributors
Author:
Yu-Su Chen
Author:
David W. Allen
Author:
Mateusz Pitak
Author:
Neil A. Cross
Author:
Neil Bricklebank
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