Doctor of Philosophy (PhD)



Document Type



This work involves the investigation of a group of uniform materials based on organic salts (GUMBOS) as matrices for matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF) for analysis of hydrophobic biomolecules. GUMBOS are new class of materials that show great promise as MALDI matrices because they are able to form a thin-layer on the MS target, thereby enhancing the sample homogeneity, signal intensity, and shot-to-shot reproducibility. The detection of hydrophobic peptides using MALDI-TOF MS remains a challenge because the majority of matrices utilized are hydrophilic thereby exhibiting low affinity for hydrophobic molecules. To address this, I have developed novel matrices of varying hydrophobicity based on aminopyrine (AP) to enhance the detection of such molecules. In the first part of this work, I outline the synthesis of a series of AP-based GUMBOS in which various counter-ions such as chloride, ascorbate, and bis(trifluoromethane) sulfonamide were used to tune the hydrophobicity of a matrix. The hydrophobicities of these compounds relative to á-cyano-4-hydroxycinnamic acid (CHCA), a common MALDI matrix, indicated that the AP-based GUMBOS can be tuned to greater hydrophobicity than CHCA. In addition, a clear trend was observed between the signal intensity of the hydrophobic peptides and the hydrophobicity of the matrix. In the second part of this work, I present a unique approach for predicting matrix-analyte interactions in MALDI using fluorescence spectroscopy. Interactions of analytes with matrices that are composed of AP and AP-based GUMBOS were investigated using a hydrophobic (gramicidin) and a hydrophilic peptide (angiotensin II). Fluorescence anisotropy and Scatchard analysis were used to investigate the interaction between matrices and peptides. Hydrophobic AP and AP-based GUMBOS revealed stronger interactions with hydrophobic peptides and enhanced detection of these peptides, which correlate well with the MALDI MS results. Finally, I have synthesized a hydrophobic GUMBOS-based matrix using CHCA and oleylamine (OA). The [OA][CHCA] GUMBOS was used as a matrix for MALDI MS for the detection of lipids in tissues and compared with 2,5-dihydroxybenzoic acid (DHB) had better signal reproducibility and improved homogeneity. These enhancements were used to examine the distribution and localization of different classes of lipids in tissue.



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Committee Chair

Warner, Isiah



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Chemistry Commons