| 研究実績の概要 |
In order to enable these clusters to be employed in biological media, we prepared unsymmetrical NHC-thiol ligands with a carboxylic acid on the backbone. Reaction of the unsymmetrical bis-alkylated benzimidazolium bromide with potassium thioacetate followed by a reaction with Au(SMe2)Cl/K2CO3 in acetone at 60°C afforded the thioacetyl derivative and its gold(I) complex, respectively. Basic ester hydrolysis conditions hydrolyzed both the ethyl ester and thioacetyl groups, affording complex.
However, the last step proved problematic, as NMR and mass spectroscopic analysis showed that hydrolysis gave dimeric species, which could not be converted into nanoparticles by reduction. Thus, we changed our plan such that thioacetate and ester groups were first hydrolyzed under basic conditions at room temperature in the presence of additional unligated gold, and then reduced by NaBH4 without isolation of the intermediate species. This method resulted in hydrolysis of both the ethyl ester and thioacetate groups, and, formation of (NHC-S)-Au nanoparticles as determined by attained water-solubility and TEM analyses, respectively. Reduction of the NHC-Br precursor in the presence of additional Au3+ ions on the other hand, produced larger nanoparticles with an SPR band at ca. 510 nm. The size of the nanoparticles could be affected by the choice of solvent or changing the reaction time. The produced nanoparticles were highly monodisperse in all cases.
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| 今後の研究の推進方策 |
In future work, we will employ amide coupling to enable the transformation of surface carboxylates to amides. Once we have successfully introduced this functionality, we will turn to the introduction of more biologically relevant compounds, such as amino acids and small peptides that are known to be tumor targeting agents. Once this is accomplished, we will study the stability of the resulting functionalized nanoparticles in simulated bio fluids and then will examine their ability to bind to tumors selectively in vivo employing mouse models. In long term studies, we will prepare nanoparticles with a mixture of tumor targeting groups and drugs to shrink/treat tumors.
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