4-Phenyl-α-cyanocinnamic Acid Amide: Screening for a Negative Ion Matrix for MALDI-MS Imaging of Multiple Lipid Classes

Abstract

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has become a method of choice in lipid analysis, as it provides localization information for defined lipids that is not readily accessible with nonmass spectrometric methods. Most current MALDI matrices have been found empirically. Nevertheless, preferential matrix properties for many analyte classes are poorly understood and may differ between lipid classes. We used rational matrix design and semiautomated screening for the discovery of new matrices suitable for MALDI-IMS of lipids. Utilizing Smartbeam- and nitrogen lasers for MALDI, we systematically compared doubly substituted α-cyanocinnamic acid derivatives (R(1)-CCA-R(2)) with respect to their ability to serve as negative ion matrix for various brain lipids. We identified 4-phenyl-α-cyanocinnamic acid amide (Ph-CCA-NH2) as a novel negative ion matrix that enables analysis and imaging of various lipid classes by MALDI-MS. We demonstrate that Ph-CCA-NH2 displays superior sensitivity and reproducibility compared to matrices commonly employed for lipids. A relatively small number of background peaks and good matrix suppression effect could make Ph-CCA-NH2 a widely applicable tool for lipid analysis.

Quantitative imaging mass spectrometry of renal sulfatides: validation by classical mass spectrometric methods

“…For this compound, we identifi ed the individual spectra/locations with highest intensity on the tissue section and set its value as maximum color code intensity for all sulfatides. With these settings, the resulting pictures suggested a prominent expression of sulfatides with C22-and C24-acyl chains 3 (sulfatides with 42 and 44 C-atoms in their ceramide moiety), especially as compared with those with a C18-acyl chain (sulfatides with 36 C-atoms in their ceramide moiety). Furthermore, the pictures imply a similar high sulfatide concentration in the papillae and medulla, although the ceramide anchors contain a different type of acyl chain in these two regions ( Fig.…”

“…To compare these results with the other two MS methods, MALDI on-target MS and UPLC-ESI-MS 2 , renal cortex, medulla, and papillae were dissected carefully with a scalpel followed by lipid extraction and quantifi cation of the sulfatide compositions using internal sulfatide standards. 3 These acyl chain lengths are derived from the molecular ion weight when assuming the most prominent sphingoid base, C18-sphingosine, as part of the structure. Our recent ESI-MS 2 data of the precursors ceramide and galactosylceramide support the abundant presence of C18-sphingosine in total renal extracts ( 43 ).…”

“…Mammalian kidneys are rich in sulfatides. Like human kidneys, mouse or rat kidneys also contain the two simple sulfatides SM4s and lactosylceramide II 3 -sulfate (SM3 ) ( Fig. 1 ).…”

“…However, mouse and rat additionally express more complex sulfatides ( 29 ). By far, the most abundant sulfatide is in mouse SM4s, followed by SM3 and minor amounts of gangliotetraosylceramide II 3 -, IV 3 -bis sulfate ( 30 ). Depending on their sulfated glycan moiety, sulfatides are differentially distributed in the kidney (31)(32)(33).…”

Investigation of 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione as a Matrix for Analyses of Biogenic Monoamine Transmitters Using MALDI-MS

“…The discovery of new matrices suitable for the detection of LMWCs could allow for neurotransmitter analysis. Efforts have been made to discover new matrices by modifying functional groups of the α-cyanocinnamic acid core unit, for example, 4-chloro-α-cyanocinnamic acid by Jaskolla et al, 11 4-phenyl-α-cyanocinnamic acid amide by Fülöp et al,12 and (E)-propyl-α-cyano-4-hydroxyl cinnamylate by Wang et al 13 In continuing efforts 14 to develop new matrices suitable for the detection of LMWCs, we designed and screened benzylidene-2,4-thiazolidinedione (BTD) derivatives (BTDs) as new matrix candidates. BTD has physicochemical properties equivalent to those of CHCA because 2,4-thiazolidinedione is a carboxylic acid isostere.…”