title: Structure-performance relationships of phenyl cinnamic acid derivatives as MALDI-MS matrices for sulfatide detection.
abstract: A key aspect for the further development of matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (MS) is a better understanding of the working principles of MALDI matrices. To address this issue, a chemical compound library of 59 structurally related cinnamic acid derivatives was synthesized. Potential MALDI matrices were evaluated with sulfatides, a class of anionic lipids which are abundant in complex brain lipid mixtures. For each matrix relative mean S/N ratios of sulfatides were determined against 9-aminoacridine as a reference matrix using negative ion mass spectrometry with 355 and 337 nm laser systems. The comparison of matrix features with their corresponding relative mean S/N ratios for sulfatide detection identified correlations between matrix substitution patterns, their chemical functionality, and their MALDI-MS performance. Crystal structures of six selected matrices provided structural insight in hydrogen bond interactions in the solid state. Principal component analysis allowed the additional identification of correlation trends between structural and physical matrix properties like number of exchangeable protons at the head group, MW, logP, UV-Vis, and sulfatide detection sensitivity. Graphical abstract Design, synthesis and mass spectrometric evaluation of MALDI-MS matrix compound libraries allows the identification of matrix structure - MALDI-MS performance relationships using multivariate statistics as a tool.
authors.affiliation: Aalen University of Applied Science, Beethovenstr. 1, 73430, Aalen, Germany.|Applied Research Center in Biomedical Mass Spectrometry (ABIMAS), Paul-Wittsack-Straße 10, 68163, Mannheim, Germany.
authors.forename: Suparna
authors.initials: S
authors.lastname: Tambe
authors.affiliation: Aalen University of Applied Science, Beethovenstr. 1, 73430, Aalen, Germany.|Applied Research Center in Biomedical Mass Spectrometry (ABIMAS), Paul-Wittsack-Straße 10, 68163, Mannheim, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Blott
authors.affiliation: Applied Research Center in Biomedical Mass Spectrometry (ABIMAS), Paul-Wittsack-Straße 10, 68163, Mannheim, Germany.|Instrumental Analysis and Bioanalysis, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Fülöp
authors.affiliation: Aalen University of Applied Science, Beethovenstr. 1, 73430, Aalen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Spang
authors.affiliation: Aalen University of Applied Science, Beethovenstr. 1, 73430, Aalen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Flottmann
authors.affiliation: Institute for Organic Chemistry, Karlsruhe Institute for Technology, Fritz Haber Weg 6, South Campus, Building 30.42, 76131, Karlsruhe, Germany.|Institute of Toxicology and Genetic, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.affiliation: Applied Research Center in Biomedical Mass Spectrometry (ABIMAS), Paul-Wittsack-Straße 10, 68163, Mannheim, Germany.|Instrumental Analysis and Bioanalysis, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hopf
authors.affiliation: Aalen University of Applied Science, Beethovenstr. 1, 73430, Aalen, Germany. hans-dieter.junker@hs-aalen.de.|Applied Research Center in Biomedical Mass Spectrometry (ABIMAS), Paul-Wittsack-Straße 10, 68163, Mannheim, Germany. hans-dieter.junker@hs-aalen.de.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Junker
mesh_terms: D002934:Cinnamates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D025341:Principal Component Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013433:Sulfoglycosphingolipids / Q000032:analysis*
chemical_list: D002934:Cinnamates; D013433:Sulfoglycosphingolipids; C029010:cinnamic acid
keywords: MALDI mass spectrometry; MALDI matrix; Principal component analysis; Structure-performance relationships; Sulfatide; X-ray crystal structure