The rates of hydrolysis of thymidyl-3',5'-thymidine-H-phosphonate: the possible role of nucleic acids linked by diesters of phosphorous acid in the origins of life.

Thymidyl-3',5'-thymidine H-phosphonate undergoes acid, base, and water-catalyzed hydrolysis. The products were 3'-thymidine H-phosphonate, 5'-thymidine H-phosphonate, and thymidine in a ratio of 1:1:2. The rate constants are 1.8 x 10(-3) M-1 sec-1, 7.2 x 10(3) M-1 sec-1, and 1.5 x 10(6) sec-1 for acid, base and water catalysis, respectively. These values are comparable with previous reports for the rates of hydrolysis of simple dialkyl esters of phosphorous acids. The Arrhenius activation energy for the base-catalyzed reaction is 20 kcal/mol. and the enthalpy and entropy of activation are 19 kcal/mol and -14 eu., respectively. The Gibbs free energy of activation is 23 kcal/mol. The rate constants suggest that nucleic acids linked by diesters of phosphorous acid hydrolyze too rapidly in aqueous solution to have accumulated in useful amounts on the primitive Earth.