Species-specific second-order rate constants for the reactions of eight model sulfoxides with hypochlorous acid (kHOCl) were determined to be in the range of 2.7 M-1 s-1 to 5.8 × 103M-1 s-1. A quantitative structure-activity relationships (QSAR) with Taft σ* constants was developed based on eight measured kHOCl-values, showing a good linear correlation (R2 = 0.89) with a negative slope ρ = -1.5 typical for electrophilic reactions. The reaction is mainly controlled by HOCl, with a minor contribution of OCl-. The contributions of other reactive chlorine species (e.g., Cl2 and Cl2O) to the overall kinetics are only 7 % for Cl2O and 5 % for Cl2 under typical drinking water treatment conditions. A combination of several analytical methods (HPLC-MS/MS, HPLC-ICP-MS/MS, and NMR) was applied for the identification of transformation products. Major transformation products from the reactions of chlorine with sulfoxides are sulfones, Cl-substituted sulfoxides, aldehydes, and sulfonic acids potentially formed via a transient chlorosulfonium cation. In general, sulfoxides react more readily with chlorine compared to bromine. This might be caused by a partial positive charge on the sulfur which leads to a stronger interaction with Cl in HOCl having a smaller partial positive charge than Br in HOBr. The ratios of the species-specific second-order rate constants for the reactions of the selected sulfoxides with chlorine or bromine (kHOCl/kHOBr) range from 6 to 480. For sulfoxide compounds with strong electron-withdrawing substituents the reaction occurs most likely via a carbanion intermediate for which the reaction with HOBr is preferred, resulting in a kHOCl/kHOBr = 0.8.
High molecular weight proteins are present abundantly in viperid venoms. The amino acid sequence can be highly variable, contributing to the structure and function diversity of snake venom protein. However, this variability remains poorly understood in many species. The study investigated the venom protein variability in a distinct clade of Asian pit vipers (Trimeresurus species complex) through comparative proteomics, applying gel electrophoresis (SDS-PAGE), liquid chromatography-tandem mass spectrometry (LCMS/MS), and bioinformatic approaches. The proteomes revealed a number of conserved protein families, within each are variably expressed protein paralogs that are unrelated to the snake phylogeny and geographic origin. The expression levels of two major enzymes, i.e., snake venom serine proteinase and metalloproteinase, correlate weakly with procoagulant and hemorrhagic activities, implying co-expression of other functionally versatile toxins in the venom. The phospholipase A2 (PLA2) abundance correlates strongly with its enzymatic activity, and a unique phenotype was discovered in two species expressing extremely little PLA2. The commercial mono-specific antivenom effectively neutralized the venoms' procoagulant and hemorrhagic effects but failed to inhibit the PLA2 activities. Instead, the PLA2 activities of all venoms were effectively inhibited by the small molecule inhibitor varespladib, suggesting its potential to be repurposed as a highly potent adjuvant therapeutic in snakebite envenoming.
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