Toward the Rational Design of Universal Dual Polarity Matrix for MALDI Mass Spectrometry

Abstract

A series of novel anthranilic acid derivatives I–IV, of which COOH-NH2 (I) and COOH-NHMe (IV) are endowed with acid and base bifunctionality, were designed and synthesized for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry applications in dual polarity molecular imaging of biological samples, particularly for lipids. The heat of protonation, deprotonation, and proton transfer reaction as well as the capability of analyzing biomolecules in both positive and negative ion modes for I–IV were systematically investigated under standard 355 nm laser excitation. The results indicate correlation between dual polarity and acid–base property. Further, COOH-NHMe (IV) showed a unique performance and was successfully applied as the matrix for MALDI-TOF mass spectrometry imaging (MSI) for studying the mouse brain. Our results demonstrate the superiority of COOH-NHMe (IV) in detecting more lipid and protein species compared to commercially available matrices. Moreover, MALDI-TOF MSI results were obtained for lipid distributions, making COOH-NHMe (IV) a potential next generation universal matrix.

Multifunctional Reactive MALDI Matrix Enabling High-Lateral Resolution Dual Polarity MS Imaging and Lipid C═C Position-Resolved MS2 Imaging

“…Novel tailormade matrices, like acid/base bifunctional MALDI matrices, improve the detection of positive/negative ions. 41 MALDI matrices for low-molecular-weight compounds were recently reviewed. 42 However, simultaneous detection of lipids in both ion modes, DB-position assignment, and highresolution MALDI-MSI has not been achieved yet.…”

“…MALDI matrices typically used for high-resolution MSI measurements, such as 2,5-dihydroxybenzoic acid or 9-aminoacridine, yield best results in positive- or negative-ion mode. Novel tailormade matrices, like acid/base bifunctional MALDI matrices, improve the detection of positive/negative ions . MALDI matrices for low-molecular-weight compounds were recently reviewed .…”

Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI

“…Huang and coworkers [30] rationally designed and synthesized a series of novel matrix candidates, including 2-(methylamino)benzoic acid (COOH-NHMe), candidate as a MALDI matrix for imaging. The matrix COOH-NHMe was synthesized by adding a methyl group to anthranilic acid using CH 3 I in basic conditions.…”

Utilizing AgNPt-SALDI to Classify Edible Oils by Multivariate Statistics of Triacylglycerol Profile

“…The current study focuses on the classification of edible oils from plant sources with independent production processes to examine their adulteration. A rapid and robust method, matrix-assisted laser desorption/ionization (MALDI), is suitable for oil sample analysis [ 14 , 15 , 16 , 17 , 18 ]. In a 2015 study, Ng et al [ 19 ] established a preliminary MALDI-MS spectral database for the classification of edible oils using a hierarchical clustering analysis (HCA).…”