Towards the rationalization of the MALDI process: a combined mass spectrometry/solid-state NMR approach

Abstract

Molecular organization of MALDI samples is suspected to play a major role in the ionization process. Using solvent-free conditions to prepare polymer samples to be mass analyzed, we show here that the grinding time influenced not only the quality of MALDI data but also the nature of detected adducts. In this context, molecular organization of these MALDI samples was studied by solid-state NMR, due to the ability of this technique to reveal changes in the local nuclear environment in solids. The model system investigated here was composed of 2,5-DHB as the matrix, a small poly(ethylene oxide) (PEG) as the analyte and cesium chloride as the cationizing agent, allowing ¹H, ¹³C and ¹³³Cs sites to be directly probed using NMR. To ensure reproducible data, the vortex method was chosen to grind the sample components in the solid state. Three different phases within the MALDI samples were evidenced through NMR. After grinding the three sample components for short times (ca. 2 min), the solid was composed of two phases, a crystalline 2,5-DHB phase and a matrix–PEG co-crystal. In spite of the addition of a cesium salt in the ternary mixture, laser irradiation of these samples only produced polymer sodium adducts. In contrast, longer grinding times (ca. 16 min), shown to promote the formation of a third phase composed of a matrix–salt co-crystal, allowed optimal production of PEG cesium adducts. Water molecules were evidenced for the first time to be part of the MALDI sample. Water could only be observed in the 2,5-DHB–CsCl crystalline complex and its presence in the grinding atmosphere was shown to be necessary for this complex to form. The variety of structural information obtained by solid-state NMR on the investigated model sample showed how this technique can be successfully employed to gain new insights into the MALDI mechanism.