3-(2'- Deoxy-beta-D-erythro-pentofuranosyl) pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M(1)dG undergoes hydrolytic ring-opening to N-2-oxopropenyl-deoxyguanosine (N(2)OPdG) under basic conditions. We report that ring-opening of M(1)dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N(2)OPdG(-) to be the only product of M(1)dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M-1 s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M-1 at 25 degreesC. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M-1. Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M(1)dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M(1)dG at neutral pH.