Purine bases such as purine, adenine, hypoxanthine, and mercaptopurine are known to exist in several tautomeric forms. Characterization of their tautomeric equilibria is important not only for predicting the regioselectivity of their N‐alkylation reactions, but also for gaining knowledge of the patterns with which these compounds of significant biological activity form hydrogen bonds with their biological targets. The tautomeric equilibria of purine and some purine derivatives in methanol and N,N‐dimethylformamide solutions were investigated by low‐temperature 1H and 13C NMR spectroscopy. The N(7)H and N(9)H tautomeric forms were quantified by integrating the individual 1H NMR signals at low temperatures. The Gibbs free energy differences were calculated and the effects of substitution on the N(7)H/N(9)H ratio discussed. A previously published theoretically predicted mechanism of the tautomeric exchange is compared with our measurements in deuteriated solvents. The influence of concentration on the temperature of coalescence indicates that supramolecular clusters play a significant role in this proton transfer process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A range of purine derivatives modified at position 6 of the basic purine skeleton exhibit a variety of biological activities. Several derivatives are used or tested nowadays for pharmacological treatments. The present work aims to analyze the effects of substituents on the electron distribution in the purine core as reflected by NMR chemical shifts. We collected a comprehensive set of experimental NMR data for a variety of 6-substituted purines (-NH(2), -NHMe, -NMe(2), -OMe, -Me, -CCH, and -CN) and determined the molecular and crystal structures of three derivatives (-NHMe, -CCH, and -CN) by X-ray diffraction. The density-functional methods calibrated in our recent study (Phys. Chem. Chem. Phys., 2010, 12, 5126) have been employed to enable understanding of the substituent-induced changes in the NMR chemical shifts of the atoms in the purine skeleton. Analyses of the nuclear shielding using localized molecular orbitals (LMOs), specifically the natural LMOs (NLMOs) and Pipek-Mezey LMOs, were used to break down the values of the isotropic (13)C and (15)N NMR chemical shifts and the chemical shift tensors into the contributions of the individual LMOs. The experimental and calculated trends in the chemical shift of the N-3 atom correlate nicely with the Hammett constants (σ(para)) and the calculated natural charges on N-3, whereas the contributions of the LMOs to the N-1 and C-6 chemical shifts are found to be more complex.