Investigation and optimization of parameters affecting the multiply charged ion yield in AP-MALDI MS

Liquid matrix-assisted laser desorption/ionization (MALDI) allows the generation of predominantly multiply charged ions in atmospheric pressure (AP) MALDI ion sources for mass spectrometry (MS) analysis. The charge state distribution of the generated ions and the efficiency of the ion source in generating such ions crucially depend on the desolvation regime of the MALDI plume after desorption in the AP-tovacuum inlet. Both high temperature and a flow regime with increased residence time of the desorbed plume in the desolvation region promote the generation of multiply charged ions. Without such measures the application of an electric ion extraction field significantly increases the ion signal intensity of singly charged species while the detection of multiply charged species is less dependent on the extraction field. In general, optimization of high temperature application facilitates the predominant formation and detection of multiply charged compared to singly charged ion species. In this study an experimental setup and optimization strategy is described for liquid AP-MALDI MS which improves the ionization effi- ciency of selected ion species up to 14 times. In combination with ion mobility separation, the method allows the detection of multiply charged peptide and protein ions for analyte solution concentrations as low as 2 fmol/lL (0.5 lL, i.e. 1 fmol, deposited on the target) with very low sample consumption in the low nL-range

Intermolecular dissociation energies of hydrogen-bonded 1-naphthol complexes

We have measured the intermolecular dissociation energiesD0of supersonically cooled 1-naphthol(1NpOH) complexes with solvents S = furan, thiophene, 2,5-dimethylfuran, and tetrahydrofuran. Thenaphthol OH forms non-classical H-bonds with the aromaticπ-electrons of furan, thiophene, and2,5-dimethylfuran and a classical H-bond with the tetrahydrofuran O atom. Using the stimulated-emission pumping resonant two-photon ionization method, the ground-stateD0(S0) values werebracketed as 21.8±0.3 kJ/mol for furan, 26.6±0.6 kJ/mol for thiophene, 36.5±2.3 kJ/mol for2,5-dimethylfuran, and 37.6±1.3 kJ/mol for tetrahydrofuran. The dispersion-corrected density func-tional theory methods B97-D3, B3LYP-D3 (using the def2-TZVPP basis set), andωB97X-D [usingthe 6-311++G(d,p) basis set] predict that the H-bonded (edge) isomers are more stable than the faceisomers bound by dispersion; experimentally, we only observe edge isomers. We compare the cal-culated and experimentalD0values and extend the comparison to the previously measured 1NpOHcomplexes with cyclopropane, benzene, water, alcohols, and cyclic ethers. The dissociation energiesof the nonclassically H-bonded complexes increase roughly linearly with the average polarizabilityof the solvent, ̄α(S). By contrast, theD0values of the classically H-bonded complexes are larger,increase more rapidly at low ̄α(S), but saturate for large ̄α(S). The calculatedD0(S0) values forthe cyclopropane, benzene, furan, and tetrahydrofuran complexes agree with experiment to within1 kJ/mol and those of thiophene and 2,5-dimethylfuran are∼3 kJ/mol smaller than experiment. TheB3LYP-D3 calculatedD0values exhibit the lowest mean absolute deviation (MAD) relative toexperiment (MAD = 1.7 kJ/mol), and the B97-D3 andωB97X-D MADs are 2.2 and 2.6 kJ/mol,respectively

Imaging Mass Spectrometry: Hype or Hope?

Imaging mass spectrometry is currently receiving a significant amount of attention in the mass spectrometric community. It offers the potential of direct examination of biomolecular patterns from cells and tissue. This makes it a seemingly ideal tool for biomedical diagnostics and molecular histology. It is able to generate beautiful molecular images from a large variety of surfaces, ranging from cancer tissue sections to polished cross sections from old-master paintings. What are the parameters that define and control the implications, challenges, opportunities, and (im)possibilities associated with the application of imaging MS to biomedical tissue studies. Is this just another technological hype or does it really offer the hope to gain new insights in molecular processes in living tissue? In this critical insight this question is addressed through the discussion of a number of aspects of MS imaging technology and sample preparation that strongly determine the outcome of imaging MS experiments