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• 1. [Article] Development of Tools for Understanding Biological Sulfur Chemistry

  Hydrogen sulfide (H2S) is an important biomolecule for its role in mediating redox homeostasis and signaling biological processes. The study of biological sulfide is currently impeded by a lack of tools ...

  Citation × Citation Citation Abstract Copy Title: Development of Tools for Understanding Biological Sulfur Chemistry Author: Bailey, Thomas Year: 2016 Hydrogen sulfide (H2S) is an important biomolecule for its role in mediating redox homeostasis and signaling biological processes. The study of biological sulfide is currently impeded by a lack of tools available that adequately address the questions currently facing the field. The most pressing of these questions are: how does H2S signal biological processes. To produce tools for studying H2S, chemiluminescent scaffolds were designed to study both H2S producing enzymes and directly measure free H2S. Additionally, small molecule organic persulfides were synthesized and characterized in order to study the properties and reactivity of H2S signaling species. By creating methods to directly measure biological H2S and creating model systems to investigate the active signaling species, the biological reactivity of H2S can be better understood. The luminescent methods for detecting H2S were developed in order to avoid photodecomposition inherent with fluorescent methods while still providing a spectroscopic readout for performing measurements in cells. D-cysteine concentrations can be measured using luciferin bioluminescence, and utilized to back out the H2S producing activity of DAO. Free H2S was measured using luminol derived chemiluminescence. The luminol scaffolds were studied in depth to determine what makes an H2S probe selective for H2S in order to inform the design of future H2S probes. Sulfide signaling processes were investigated using organic persulfide model systems. We found that under reducing conditions persulfides liberate free H2S, and that under basic conditions they decompose. The decomposition pathway is governed by substitution at the -carbon, which dictates the steric accessibility of the inner sulfur atom to act as an electrophile. Persulifdes do not react with acids, and are easily tagged by electrophiles to form disulfides. Persulfides are sufficiently reducing to generate NO from nitrite, facilitating cross-talk between multiple signaling species. This cross talk is mediated by formation of perthionitrite, which may function as an independent signaling species. Title: Development of Tools for Understanding Biological Sulfur Chemistry Author: Bailey, Thomas Year: 2016 Hydrogen sulfide (H2S) is an important biomolecule for its role in mediating redox homeostasis and signaling biological processes. The study of biological sulfide is currently impeded by a lack of tools available that adequately address the questions currently facing the field. The most pressing of these questions are: how does H2S signal biological processes. To produce tools for studying H2S, chemiluminescent scaffolds were designed to study both H2S producing enzymes and directly measure free H2S. Additionally, small molecule organic persulfides were synthesized and characterized in order to study the properties and reactivity of H2S signaling species. By creating methods to directly measure biological H2S and creating model systems to investigate the active signaling species, the biological reactivity of H2S can be better understood. The luminescent methods for detecting H2S were developed in order to avoid photodecomposition inherent with fluorescent methods while still providing a spectroscopic readout for performing measurements in cells. D-cysteine concentrations can be measured using luciferin bioluminescence, and utilized to back out the H2S producing activity of DAO. Free H2S was measured using luminol derived chemiluminescence. The luminol scaffolds were studied in depth to determine what makes an H2S probe selective for H2S in order to inform the design of future H2S probes. Sulfide signaling processes were investigated using organic persulfide model systems. We found that under reducing conditions persulfides liberate free H2S, and that under basic conditions they decompose. The decomposition pathway is governed by substitution at the -carbon, which dictates the steric accessibility of the inner sulfur atom to act as an electrophile. Persulifdes do not react with acids, and are easily tagged by electrophiles to form disulfides. Persulfides are sufficiently reducing to generate NO from nitrite, facilitating cross-talk between multiple signaling species. This cross talk is mediated by formation of perthionitrite, which may function as an independent signaling species. Close