Hydrogen sulfide is an important gasotransmitter that has a wide range of medicinal properties, ranging from treating cardiovascular disease to targeting cancer cells. Since hydrogen sulfide is a gas, scientists use chemicals such as organotrisulfides and organopolysulfides to release hydrogen sulfide locally in a controlled manner. These chemicals release hydrogen sulfide in the presence of an intracellular thiol such as cysteine or glutathione. Although the hydrogen sulfide releasing properties of organotrisulfides and polysulfides have been studied extensively, their stabilities under different conditions, particularly biological conditions, have not. Three biologically relevant, symmetrical trisulfides were synthesized from cysteine, glutathione, and N-acylcysteine; and a tetrasulfide from N-acylcysteine was synthesized to investigate the stabilities of polysulfides. Using 1H NMR spectroscopy, the stability of these trisulfides and tetrasulfide were investigated at various conditions ranging from acidic to basic aqueous solutions and in the presence of different functional groups. Amines had a large impact on the stability of the organotrisulfides and tetrasulfide, causing significant degradation in each. Amines also catalyzed a reaction between the disulfides and elemental sulfur which lead to an equilibrium between disulfides and trisulfides. Estimated rate constants of the degradation of the trisulfides in the presence of thiols were obtained. The rates varied by two orders of magnitude, with cysteine trisulfide being the fastest at 0.78 min-1 and glutathione trisulfide being the slowest at 7.2x10-3 min-1. The amount of hydrogen sulfide produced was quantified using a hydrogen sulfide electrode. In the presence of a thiol, all three organotrisulfides produced near quantitative amounts of hydrogen sulfide on the time scale of hours.

Stability of biologically relevant organotrisulfides and their hydrogen sulfide releasing properties

ACS Spring Meeting 2021

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