Synthesis and Evaluation of Organic Sources of Reactive Sulfur Species.

Abstract

Abstract: Sulfur dioxide (SO2) is an environmental pollutant that is also produced during metabolism of sulfur containing amino acids. At elevated levels, SO2 is known to cause biomacromolecular damage and is hence considered a reactive sulfur species. In contrast, SO2 is used in the food industry as a preservative and an anti-bacterial agent. In order to better understand the roles of this gaseous entity, reliable sources of SO2 are necessary. Further, controlled generation of SO2 might have applications in developing novel therapeutic agents as well. Biological studies have thus far relied on gaseous SO2 or a complex formulation of inorganic sulfites and both methods are not suitable for exploration of therapeutic applications. Here, we have developed small molecule-based strategies to generate SO2 under physiological conditions. First, we present results of the synthesis and evaluation of benzosultines as SO2 donors. These compounds are stable powders but upon dissolution in buffer decompose to produce SO2 at tuneable rates. Next, we investigated cyclic sulfite diesters as SO2 donors and we find that these compounds are stable in organic media but when dissolved in buffer these compounds produced SO2 in excellent yield. A library of 2,4-dinitrophenylsulfonamides, which can be activated by biological thiols to produce SO2 were prepared. The half-lives of decomposition of these compounds could be tuned by changing the basicity of the nitrogen bearing the sulfonyl group. Finally in order achieve site-specific delivery, benzothiophene,1,3-dihydro-2,2-dioxides were prepared and found to be otherwise stable but when activated by light produced SO2. Taken together, we have developed several methodologies for generation of sulfur dioxide, a reactive sulfur species, in a controlled manner and investigated the structural aspects of decomposition and SO2 release.