Arsonium and phosphonium-functionalized gold nanoparticles for mitochondria targeted therapeutics

This thesis presents a body of original research describing the synthesis, characterisation and biological properties of novel arsonium- and phosphonium- alkylthiosulfate zwitterions and thioacetate salts and gold nanoparticles functionalized with triphenylarsoniumpropylthiolate ligands. Chapter 1 presents a systematic literature review of the preparation of functionalized gold nanoparticles, their biomedical properties, the biological applications of phosphonium and arsonium ions and phosphonium-functionalized nanomaterials. Details of the analytical methods employed to characterize all the compounds produced in this study are outlined in chapter 2. Chapter 3 reports the synthesis of the triphenylarsoniopropylthiosulfate zwitterion and ω- thioacetylpropyl(triphenyl)arsonium bromide salt. Both compounds have been characterized spectroscopically and by single crystal X-ray diffraction. The thiosulfate group of the triphenylarsoniopropylthiosulfate zwitterion and the thioacetate group of the ω- thioacetylpropyl(triphenyl)arsonium salt undergo reductive cleavage, forming the corresponding triphenylarsoniumpropylthiolate ions that attach to the surface of gold in a modification of the established Brust-Schiffrin method for preparing gold nanoparticles. TEM studies show the triphenylarsonium-functionalized gold nanoparticles to be spherical with diameters of c.a. 3nm. The presence of the triphenylarsonium groups has been confirmed by Raman and XPS spectroscopy and mass spectrometry. It also describes the synthesis, characterisation and biological properties of a family of phosphoniopropylthiosulfate zwitterions and ω-thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine. The IC50 values of the triphenylarsoniopropylthiosulfate zwitterion, ω-thioacetylpropyl- (triphenyl)arsonium bromide salt, triphenylarsonium-functionalized gold nanoparticles and family of phosphoniopropylthiosulfate zwitterions and ω- thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine have been determined against PC3 prostate cancer cells using MTT and CellTiter-Glo assays and are reported in Chapter 4. The uptake of the triphenylarsonium-functionalized gold nanoparticles by PC3 and Human Fibroblast cells has also been determined by ICP-OES spectroscopy.