Abstract Title
The Influence of Hydrogen Bonding Effects on the Reactivity of Zinc Hydrosulfide Complexes
Additional Funding Sources
The project described was supported by Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Nos. P20GM103408 and P20GM109095, and National Science Foundation S-STEM Gateway Scholarships in Biological Sciences under Grant Award No. DUE-1644233. We also acknowledge support from the Biomolecular Research Center at Boise State with funding from the National Science Foundation, Grant Nos. 0619793 and 0923535, the M.J. Murdock Charitable Trust, and the Idaho State Board of Education.
Abstract
Carbonic Anhydrase (CA) is a zinc-containing enzyme that is found within all mammalian species, plants, and algae. Its primary mammalian function is to catalyze the reversible hydration of carbon dioxide (CO2) to form bicarbonate (HCO3-), where bicarbonate is transported to the lungs and converted back by CA to CO2 and exhaled. Another heterocumulene that can bind to the active site of CA is carbonyl sulfide (COS). When COS reacts with CA, hydrogen sulfide gas (H2S) is produced. H2S is an important molecule in biomedicine since it is a signaling molecule/ gastrotransmitter in the body. The primary focus of our research is to fundamentally understand the mechanism of COS activation, and to ultimately answer the question: How does desulfurization occur at a physiological pH? Specifically, we wish to understand if hydrogen bonding interactions surrounding the active site of CA influence the protonation and desulfurization of hydrosulfide. To test this hypothesis, two zinc-hydrosulfide complexes have been synthesized (one with no hydrogen bond donors and the other with one hydrogen bond donor) and the pH of desulfurization was measured.
The Influence of Hydrogen Bonding Effects on the Reactivity of Zinc Hydrosulfide Complexes
Carbonic Anhydrase (CA) is a zinc-containing enzyme that is found within all mammalian species, plants, and algae. Its primary mammalian function is to catalyze the reversible hydration of carbon dioxide (CO2) to form bicarbonate (HCO3-), where bicarbonate is transported to the lungs and converted back by CA to CO2 and exhaled. Another heterocumulene that can bind to the active site of CA is carbonyl sulfide (COS). When COS reacts with CA, hydrogen sulfide gas (H2S) is produced. H2S is an important molecule in biomedicine since it is a signaling molecule/ gastrotransmitter in the body. The primary focus of our research is to fundamentally understand the mechanism of COS activation, and to ultimately answer the question: How does desulfurization occur at a physiological pH? Specifically, we wish to understand if hydrogen bonding interactions surrounding the active site of CA influence the protonation and desulfurization of hydrosulfide. To test this hypothesis, two zinc-hydrosulfide complexes have been synthesized (one with no hydrogen bond donors and the other with one hydrogen bond donor) and the pH of desulfurization was measured.