Synthesis and bioactivity of water-soluble phosphine-stabilized ultrasmall gold nanoparticles

摘要

Ultrasmall gold nanoparticles (usAuNP) with core diameters below 2 nm have attracted increasing scientific interest due to their special properties, which arise from size quantization effects. They are promising candidates for biomedical applications, because they approach the size of subcellular units. For this kind of application their bioactivity has to be evaluated. In this context this work focuses on the synthesis, characterization and bioactivity of water-soluble phosphine- and diphosphine-stabilized usAuNP. Water-soluble tetrasulfonated bis(diphenylphosphino)alkanes with different alkyl chain lengths were synthesized via the sulfonation of their water-insoluble derivatives. A reduction of AuCl3 in the presence of a tetrasulfonated diphosphine ligand yielded usAuNP with particle core diameters between 1-2 nm. Depending on the used diphosphine ligand different dipsersities were achieved. 31P-NMR spectroscopy revealed a bidentate binding of the ligand to the Au-surface as main binding motif. A ligand exchange reaction on [Au9(PPh3)8](NO3)3 with a water-soluble diphosphine ligand yielded diphosphine-stabilized usAuNP with a particle core diameter around 1 nm. However, no crystals for single-X-ray diffraction (XRD) analysis could be obtained for any of the synthesized usAuNP. The lack of precise structural information prevented their use in bioactivity studies. The synthesis of a recently described 1.1 nm sized triphenylphosphine-monosulfonate (TPPMS)-stabilized Au9-cluster was greatly improved. This particle was used in patch-clamp experiments together with TPPMS-stabilized AuNP of larger size, to evaluate their blocking potential on the human-ether-á-go-go (hERG) ion channel. Therein, AuNP with a particle core diameter of 1.4 nm showed the highest blocking effect. As an alternative to single-XRD analysis, high resolution transmission electron microscopy (HRTEM) was tested as structural characterization method. For a first evaluation of HRTEM as structural characterization method AuNP with a core diameter of 4 nm and ultrathin carbon supports were used, leading to images of the AuNP structures with a high resolution. This concludes that HRTEM might also be used as a structural characterization tool for usAuNP.