Gas-phase basicity of several common MALDI matrices measured by a simple experimental approach

Abstract

We present a combined experimental and theoretical study to determine the gas-phase basicity of several relatively small organic molecules that are used as matrices in MALDI: alpha-cyano-4-hydroxycynnamic acid (αCHCA), ferulic acid (FA), 3-hydroxypicolinic acid (HPA), sinapinic acid (SA), and 2,4,6-trihydroxyacetophenone (THAP). Our simple and fast experimental approach utilizes the ability of an electrosonic spray ionization (ESSI) source to produce high densities of gas-phase ions at ambient conditions, so that their gas-phase thermochemical properties can be probed in a bracketing-like experiment at atmospheric pressure, with no need for high vacuum. The reaction between the analyte and reference bases is monitored by a commercial mass spectrometer. We determined the following GB values of the MALDI matrices studied: 908.1 ± 0.8 (αCHCA), 863.8 ± 8.0 (FA), 876.3 ± 10.2 (HPA), 867.4 ± 1.4 (SA), and 864.2 ± 7.6 (THAP) kJ mol⁻¹. A good agreement between the experimentally measured and computationally predicted (DFT-B3LYP, G4MP2) gas-phase basicities for the studied compounds is found, except for αCHCA for which the calculations resulted in approximately 80 kJ mol⁻¹ lower GB. We attribute the observed discrepancy between the measured and calculated values to a gas-phase rearrangement of αCHCA into a heterocyclic aromatic isomer, 7-hydroxyquinoline-3-carboxylic acid (HQA). HQA is thermodynamically more stable and features higher GB than that of αCHCA (calculated at approximately 920 kJ mol⁻¹). The gas-phase basicity values of THAP and HPA are reported for the first time.