Methoxy-phenyl groups reduce the cytotoxicity and increase the aqueous solubility of phosphonium zwitterions and salts

The ability of phosphonium cations to act as intracellular transport vectors is well-established. Previous research has demonstrated that phosphonioalkylthiosulfate zwitterions, and -thioacetylalkylphosphonium salts are useful precursors for the formation of phosphonium-functionalised gold nanoparticles and enable the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this report we describe the synthesis and characterisation of a series of phosphonioalkylthiosulfate zwitterions, and-thioacetylalkylphosphonium salts derived from the methoxy-phenylphosphines tris(2,4,6-trimethoxyphenyl)phosphine, tris(2,6-dimethoxyphenyl)phosphine and tri(4-methoxyphenyl)phosphine. The methoxyphenyl-substituted phosphonium compounds show greater solubility in aqueous systems than the corresponding phenyl derivatives and cytotoxicity studies reveal that the compounds are significantly less toxic than the related triphenylphosphonium derivatives. The solid-state structures of the tris(2,4,6-trimethoxyphenyl)- and tris(2,6-dimethoxyphenyl)-phosphoniopropylthiosulfate zwitterions have been investigated by single crystal X-ray crystallography. The differences in the molecular packing of the compounds may account for greater solubility of these zwitterions in aqueous solutions

Gold nanoparticle-based colorimetric biosensors

Gold nanoparticles (AuNPs) provide excellent platforms for the development of colorimetric biosensors as they can be easily functionalised, displaying different colours depending on their size, shape and state of aggregation. In the last decade, a variety of biosensors have been developed to exploit the extent of colour changes as nano-particles (NPs) either aggregate or disperse, in the presence of analytes. Of critical importance to the design of these methods is that the behaviour of the systems has to be reproducible and predictable. Much has been accomplished in understanding the interactions between a variety of substrates and AuNPs, and how these interactions can be harnessed as colorimetric reporters in biosensors. However, despite these developments, only a few biosensors have been used in practice for the detection of analytes in biological samples. The transition from proof of concept to market biosensors requires extensive long-term reliability and shelf life testing, and modification of protocols and design features to make them safe and easy to use by the population at large. Developments in the next decade will see the adoption of user friendly biosensors for point-of-care and medical diagnosis as innovations are brought to improve the analytical performances and usability of the current designs. This review discusses the mechanisms, strategies, recent advances and perspectives for the use of AuNPs as colorimetric biosensors. Keywords: biosensors, colloids, gold nanoparticles, nanotechnology, surface plasmon resonance, enzymes, quantification

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 (omega)-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 (omega)-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 67uM and 252uM 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 (omega)-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 (omega)-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