Efficient and oxygen-independent hydrolysis of single-stranded DNA by cerium(IV) ion

Abstract

Cerium(IV) ion efficiently hydrolyses the phosphodiester linkages in DNAs, even in the absence of molecular oxygen. The pseudo first-order rate constant for the hydrolysis of thymidylyl(3′,5′)thymidine (TpT) by Ce(NH₄)₂(NO₃)₆(0.01 mol dm^–3) at pH 7 and 50 °C is 1.9 × 10^–1 h^–1(the half-life is 3.6 h), either with or without molecular oxygen. DNA hydrolysis by CeCl₃ requires molecular oxygen to convert the Ce^III ion to Ce^IV. Addition of hydrogen peroxide causes various side-reactions rather than accelerating the hydrolysis. The hydrolysis by Ce^IV proceeds via P–O scission, as confirmed by the absence of ¹⁸O incorporation into thymidine (T) during the reaction in an H₂¹⁸O–H₂¹⁶O mixture. There exists no specific base-preference in the scission, and concurrent oxidative cleavage of the deoxyribose is nil. The activity of Ce^IV is more than 200 fold greater than those of trivalent lanthanide ions and of other tetravalent ions. A significant D₂O solvent isotope effect and the pH independence of the hydrolysis rate indicate that the hydrolysis proceeds via an intramolecular attack by the Ce^IV-bound hydroxide ion and that the reaction is further assisted by the general acid catalysis of another water bound to the Ce^IV ion.