Improved Methodology for the Preparation of Water-Soluble Maleimide-Functionalized Small Gold Nanoparticles

Improved methodology to prepare maleimide-functionalized, water-soluble, small (<3 nm) gold nanoparticles using a retro-Diels-Alder strategy that we developed for similar organic-soluble AuNP's is described. Importantly, our results suggest that a recent paper by Zhu, Waengler, Lennox, and Schirrmacher describing a similar strategy gave results inconsistent with the formation of the titled maleimide-modified AuNP (Zhu, J.; Waengler, C.; Lennox, R. B.; Schirrmacher, R. Langmuir 2012, 28, 5508) as the major product, but consistent with the major product being an adduct derived from the hydrolysis of maleimide formed under the conditions used for the required deprotection of the maleimide. Our methodology provides an efficient and accessible route to pure maleimide-modified small AuNP's that circumvents the formation of the hydrolysis product. The maleimide-modified small AuNP's are versatile because they are soluble in water and in a wide range of organic solvents and their reactivity can now be properly exploited as a reactive moiety in Michael addition for bioconjugation studies in aqueous solution.