Sulfurization of H-Phosphonate Diesters by Elemental Sulfur under Aqueous Conditions

Abstract

To assess the plausibility of prebiotic nucleic acid polymerization by a sequential phosphitylation-sulfurization mechanism, the rates of hydrolysis and sulfurization of bis(2′,3′-O-methyleneadenosin-5′-yl)-H-phosphonate, a dinucleoside H-phosphonate diester, have been determined over a wide pH range (0.52-7.25) and in the presence of varying amounts (0-30 mg) of elemental sulfur. The pH-rate profile of hydrolysis resembled the one previously reported for the H-phosphonate analogue of thymidylyl-3′,5′-thymidine, with a relatively wide pH-independent region flanked by acid- and base-catalyzed regions. Sulfurization to the respective phosphorothioate diester, in turn, was found to be base-catalyzed over the entire pH range studied. Despite the facile hydrolysis of H-phosphonate diesters and the extremely low solubility of elemental sulfur in water, sulfurization and hydrolysis proceeded at comparable rates under neutral and mildly acidic conditions.