Letter pubs.acs.org/ac
Capillary Liquid Chromatography Mass Spectrometry Analysis of Intact Monolayer-Protected Gold Clusters in Complex Mixtures David M. Black,*,‡ Stephan B. H. Bach,† and Robert L. Whetten‡ ‡
Department of Physics and Astronomy, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, United States † Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, United States S Supporting Information *
ABSTRACT: In some respects, large noble-metal clusters protected by thiolate ligands behave as giant molecules of definite composition and structure; however, their rigorous analysis continues to be quite challenging. Analysis of complex mixtures of intact monolayer-protected clusters (MPCs) by liquid chromatography mass spectrometry (LC-MS) could provide quantitative identification of the various components present. This advance is critical for biomedical and toxicological research, as well as in fundamental studies that rely on the identification of selected compositions. This work expands upon the separate LC and MS results previously achieved, by interfacing the capillary liquid chromatograph directly to the electrospray source of the mass spectrometer, in order to provide an extremely sensitive, quantitative, and rapid means to characterize MPCs and their derivatives far beyond that of earlier reports. Here, we show that nonaqueous reversed-phase chromatography can be coupled to mass-spectrometry detection to resolve complex mixtures in minute (∼100 ng) samples of gold MPCs, of molecular masses up to ∼40 kDa, and with single-species sensitivity easily demonstrated for components on the level of sub-10 ng or picomole (1 pmol).
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metric detection, is a mature technology that should be well suited to this kind of characterization. Crucially, the capillary chromatographic separation can be coupled to electrospray ionization (ESI) mass spectrometric (MS) detection to provide a rapid “in-line” analysis that bypasses fraction collection and thus can be completed rapidly and reduces material consumption. Here, we report the implementation of inline liquid chromatography mass spectrometry (LC-MS) for separation and detection of intact gold MPCs with molecular mass up to 36.5 kDa, of which 77.5% is gold. Although LC-MS is routinely used for analysis of small molecules, peptides, and other biopolymers,15 we demonstrate herein how this instrumentation can also be adapted for the characterization of these significantly different types of molecules, comprising large metal-atom clusters in the core and a ligand monolayer in the mantle. Much of the MPC related liquid chromatography reported in the literature up until this point has been carried out on a preparative scale, meaning flow rates on the order of tens of milliliters per minute (mL/min) are run through a large-bore LC column, or analytical scale which works at (mL/min) mobile phase flow rates.14,16−19 Here, we make use of capillary LC,
s the synthesis of novel monolayer protected clusters (MPCs) and their respective derivatives and bioconjugates1−8 becomes ever more prevalent (from
