Triethylamine Solution for the Intractability of Aqueous Gold-Thiolate Cluster Anions: How Ion Pairing Enhances ESI-MS and HPLC of aq-Au_n(pMBA)_p

Herein we disclose methods that greatly improve the solution- and gas-phase handling properties of larger aqueous-phase gold-thiolate clusters, which previously presented extreme technical obstacles to molecular analysis and size control, even as they have enjoyed ever-wider applications in materials science and biomedicine. The methods are based upon an analogy between the polyacidic surface structure of the pMBA-protected clusters (pMBA = p-mercaptobenzoic acid) and that of oligonucleotides. A volatile ion-pairing reagent, TEA = triethylamine, greatly improves solution-phase stability near neutral pH and thus facilitates both electrospray generation of the gas-phase ions and the in-line reversed-phase ion-pairing HPLC-ESI-MS approach to analyzing complex mixtures of Au-pMBA oligomers and clusters. Previously anticipated but never established compounds, including Au₃₆(pMBA)₂₄, are thereby demonstrated. These results are in accord with recent theoretical simulations of ion pairing of model Au₁₄₄(pMBA)₆₀ clusters in aqueous solutions. This advance complements our recent work on their nonaqueous (hydrophobic) counterparts, in which redox electrochemistry is sufficient to support the efficient LC-ESI processes, enabling various precise measurements on the intact molecular ions. Here, we report (i) novel conditions for enhanced ESI generation of polyanions of the aqueous clusters and by extension (ii) a notably improved method by which mixtures of these clusters may be successfully separated and detected by ion-pair reversed-phase HPLC-MS.