1,8-Di(piperidinyl)-naphthalene – rationally designed MAILD/MALDI matrix for metabolomics and imaging mass spectrometry

Abstract

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of small molecules requires special matrices, which do not generate interfering signals below m/z 500. Here, we present 1,8-di(piperidinyl)naphthalene (DPN), a new matrix that is suitable for analytes of low molecular weight in negative ion mode and that does not generate such signals. This compound was rationally designed from parent 1,8-bis(dimethylamino)naphthalene (DMAN) by increasing the distance among the di-nitrogen-center-chelated proton and a deprotonated anion and by increasing a steric repulsion. This matrix features superior ionization properties, as its superbasic nature causes analyte molecules to be more effectively deprotonated prior to laser desorption according to the MAILD-principle (Matrix-Assisted-Ionisation/Laser-Desorption). As a result, for a wide range of analytes with varying degrees of acidity, higher signal intensity can be achieved with DPN compared to conventional “classic” matrices as well as already known MAILD-matrices. To demonstrate the applicability of DPN for metabolomical studies, we tested its performance as a matrix on biologically relevant analytes and compared the results with those obtained using established matrices. We also show the advantages of DPN for MS-imaging techniques and MALDI at atmospheric pressure (AP-MALDI). This new matrix reported here represents a considerable improvement on established MAILD-matrices in terms of sensitivity and range of potential analytes.