Comparison of the acid–base properties of purine derivatives in aqueous solution. Determination of intrinsic proton affinities of various basic sitesElectronic supplementary information (ESI) available: Figures S1 (UV absorption spectra of 9-methyladenine), S2 (spectra of 1,9-dimethyladenine), S3 (plot of absorption versus H0/pH for 1,9-dimethyladenine), S4 (spectra of 1-methyladenosine), S5 (absorption versus H0/pH for 1-methyladenosine), S6 (spectra of 7,9-dimethyladenine), S7 (absorption versus

Abstract

The acidity constants of protonated 7,9-dimethylguanine, 7-methylguanosine, 7,9-dimethylhypoxanthine, 7-methylinosine, 9-methyladenine, 1,9-dimethyladenine, 7,9-dimethyladenine and 1-methyladenosine were determined in aqueous solution at 25 °C and I = 0.1 M (NaNO3). In those instances where pKa > 2 potentiometric pH titrations were used for the determinations; when pKa < 2, UV spectrophotometric and 1H-NMR shift measurements were employed (25 °C). In these latter instances, where I is often larger than 0.1 M, the H0 scale was applied to define the H+ activity of the strong acid (HClO4; HNO3). A combination of the present results with values taken from our earlier work allowed us to quantify the intrinsic acidic properties in aqueous solution of the (N1)H0 or + and (N7)H+ sites via micro acidity constant schemes for seven purine derivatives and to calculate the tautomeric ratios regarding the monoprotonated species, that is N7–N1·H versus H·N7–N1 meaning that in one isomer H+ is at the N1 site and in the other at N7. A plot of the micro acidity constants pkN7–N1H·N7–N1, which quantify the acidity of the (N7)H+ site, versus the macro acidity constants pKa/(N1)H, which largely refer to the release of the proton from the (N1)H unit, results in a straight line for the guanine and hypoxanthine derivatives. This fact allows estimation of the micro acidity constant for any related derivative provided a value for pKa/(N1)H is known. The presented results are also meaningful for nucleic acids because they quantify the acid–base properties of their individual sites.