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.

Photoactuating Artificial Muscles of Motor Amphiphiles as an Extracellular Matrix Mimetic Scaffold for Mesenchymal Stem Cells

“…Desulfurization with triphenylphosphine in toluene gave overcrowded alkene 7, which was hydrolyzed to provide diol 8. The new MAs were obtained via two different synthetic methods: functionalization of 8 with diphenyl phosphite yielded MA P1 , 59 while MA S1 was obtained by a sulfate ester formation of 8 with a sulfur trioxide pyridine complex and subsequent hydrolysis. 60 The structures of all new compounds were established by 1 H, 13 C nuclear magnetic resonance (NMR) and high-resolution ESI mass spectrometry, and detailed synthetic procedures and data are provided in the Supporting Information (SI: pages S3−S6, Figures S9−S20).…”

Depsipeptide Nucleic Acids: Prebiotic Formation, Oligomerization, and Self-Assembly of a New Proto-Nucleic Acid Candidate

“…A number of alternatives to the phosphodiester linkage have been suggested, each with particular advantages and disadvantages. These include acetals, amides, , phosphite esters, thiophosphate esters, and carboxylic acid esters. , We recently reported that oligoesters are formed readily from α-hydroxy acids under mild drying conditions without need for a condensing agent . Furthermore, when α-hydroxy acids and α-amino acids are combined in wet–dry cycling reactions, depsipeptide oligomers (containing both ester and amide linkages) are readily formed, , which suggests depsipeptide as a candidate backbone for proto-nucleic acid oligomers.…”

“…A number of alternatives to the phosphodiester linkage have been suggested, each with particular advantages and disadvantages. These include acetals, 37 amides, 38,39 phosphite esters, 40 thiophosphate esters, 41 and carboxylic acid esters. 42,43 We recently reported that oligoesters are formed readily from αhydroxy acids under mild drying conditions without need for a condensing agent.…”

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

“…In 2016 and 2017, Lonnberg demonstrated that the sulfurization of phosphite diesters by elemental sulfur could bring about this necessary oxidation to produce phosphorothioate diesters of nucleosides that were kinetically stable to hydrolysis. , By incubating bis­(2′,3′- O -methyleneadenosin-5′-yl)- H -phosphonate in an aqueous suspension of elemental sulfur (present as S 8 ) at 60 °C with an acetate buffer, pH 4.56, sulfurization and hydrolysis were both observed (Figure ). Even though S 8 is insoluble in water, with a great enough mass of finely dispersed sulfur added to the reaction, sulfurization could outcompete hydrolysis.…”