Experimental and Computational Study of Aminoacridines as MALDI(−)-MS Matrix Materials for the Analysis of Complex Samples

Abstract

Monoaminoacridines (1-, 2-, 3-, 4-, and 9-aminoacridine) were studied for suitability as matrices in the negative ion mode matrix-assisted laser desorption/ionization mass spectrometry (MALDI(−)-MS) analysis of various samples. This is the first study to examine 1-, 2-, and 4-aminoacridine as potential matrix material candidates for MALDI(−)-MS. In addition, spectral (UV−Vis absorption and fluorescence), proton transfer-related (basicity and autoprotolysis), and crystallization properties of these compounds were characterized experimentally and/or computationally. For testing the capabilities of these aminoacridines as matrix materials, four samples related to cultural heritage materialsstearic acid, colophony resin, dyer's madder dye, and a resinous case-study sample from a shipwreckwere analyzed with MALDI(−)-MS. A novel algorithm (implemented as an executable Python script) for MS data analysis was developed to compare the five matrix materials and to help mass spectrometrists rapidly identify peaks originating from the sample and matrix material. It was determined that all five of the studied aminoacridines can successfully be used as matrix materials in MALDI(−)-MS analysis. As an interesting finding, in several cases, the best mass spectra were obtained by using a relatively small amount of matrix material mixed with an excess amount of sample. 3-and 4-aminoacridine outperformed the other aminoacridines in the ease of obtaining acceptable spectra, average number of ions identified in the mass spectra, and low dependence of the sample-to-matrix mass ratio on experimental results.

Solubility of Mono‐Aminoacridines

“…In this work, we explore solubility of five possible monoaminoacridine (AA) isomers (Figure 1). This study complements our previous works [17,18] on the use of AA isomers as matrix compounds in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Solubility is important for MALDI-MS process, where obtaining a homogenous solution of sample and matrix compound is needed for producing high-quality mass spectra.…”

“…The purities of the AAs were determined with the quantitative NMR method (qNMR, described in detail in the SI). The 1 H and 13 C NMR spectra of all five AAs have been reported in our previous publication [18] …”

“…[19][20][21] The most used of the isomers, 9-AA, also finds applications as an intracellular pH indicator, [22] topical antiseptic, [23] fluorescent dye, [24] and drug precursor. [25][26][27] The other AAs have been used less widely, [17,18] but the aminoacridine moiety itself is part of several dyes, such as acridine yellow and acridine orange. To the best of our knowledge, there is no work dedicated to the solubility of the AA isomers or closely related compounds.…”

Matrix‐assisted laser desorption/ionization matrix incorporation evaluation algorithm for improved peak coverage and signal‐to‐noise ratio in mass spectrometry imaging

“…If a bin contained several peaks in a pixel's mass spectrum, a peak with the highest SNR was used for further metric calculation. Bins contained peaks associated with the matrix, including clusters, fragments, and adducts, 30 were excluded from the datasets. The datasets with identical parameters were merged.…”

Construction of Covalent Bisubstrate Inhibitor of Protein Kinase Reacting with Cysteine Residue at Substrate-Binding Site

“…Sample solution was mixed with 2,5-dihydrobenzoic acid (2,5-DHB, Sigma-Aldrich) solution, the obtained solution was spotted onto an AB 192 + 6 spot stainless steel MALDI target plate, and the spots were dried under vacuum conditions. The matrix solution was spiked with ProteoMass Normal mass MALDI calibration kit (Sigma-Aldrich) for internal calibration of individual mass spectra …”