{'fraction_non_alphanumeric': 0.04114994363021421, 'fraction_numerical': 0.005636978579481398, 'mean_word_length': 5.598513011152416, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Next Generation Paternò-Büchi Reagents for Lipid Analysis by Mass Spectrometry.

The Paternò-Büchi (PB) reaction is a photochemical reaction involving [2+2] cycloaddition between electronically excited carbonyl and carbon-carbon double bond (C=C). It has been established as a lipid derivatization strategy, leading to confident assignment of C=C locations in lipids when coupled with tandem mass spectrometry (MS/MS). Although acetone and several aryl-containing ketones or aldehydes have been explored as the PB reagents, the chemical properties key to achieving efficient conversion and minimum side reactions remain unclear. Herein, we investigated a set of acetophenone (AP) derivatives, aiming to provide insights to the development of new PB reagents with enhanced performance for lipid analysis. For AP derivatives, we found that electron-withdrawing groups (e.g. -F, -CF3) on the benzene ring improved the overall conversion, while a bulky group at the ortho-position decreased the conversion. Norrish Type I cleavage was largely diminished; however, Norrish Type II side reaction was more competitive, producing products isomeric to the PB reaction products. Among all AP derivatives tested, 2',4',6'-trifluoroacetophenone (triFAP) showed the best performance. It offered relatively high PB yield (20-30%) for different types of C=C, high sensitivity (sub-nM) for C=C identification, and accurate isomer quantitation. Due to significantly reduced chemical interferences in shotgun analysis, triFAP provided better performance than that from acetone PB-MS/MS. Offline triFAP PB reaction was implemented in a liquid chromatography analysis workflow, which enabled large-scale identification of phospholipids including C=C location isomers from complex lipid extract.