The studies of tautomerism in 6-mercaptopurine derivatives by 1H–13C, 1H–15N NMR and 13C, 15N CPMAS-experimental and quantum chemical approach

Tautomerism in 6-mercaptopurine (6mpH), 2,6-dimercaptopurine (2,6dmp) and 6-mercaptopurine-9-riboside (6mp-9rb) was studied in the solution with 2D NMR methods-1H–13C HMBC and 1H–15N HMQC. The 15N NMR signals were assigned and the distribution of mobile protons proposed on the basis of δ13C, δ15N chemical shifts and JHC, JHN coupling constants, determined with HECADE. These heterocycles appear in DMSO-d6 as the thionic species with predominance of the following tautomers: N(1)H, N(7)H for 6mpH; N(1)H, N(3)H, N(7)H for 2,6dmp; N(1)H for 6mp-9rb. Quantum-chemical NMR calculations by GIAO method(RHF/6-31G**//B3LYP/6-31G**) allowed to evaluate the ratios of N(7)H, N(9): N(7), N(9)H tautomeric forms as ca. 3:1 for 6mpH and nearly 10:0 for 2,6dmp. The 13C and 15N CPMAS spectra were measured for solid 6mpH·H2O, anhydrous 6mpH, 2,6dmp and 6-mercaptopurinium chloride (6mpH2Cl), confirming the thionic character of all compounds. The 15N chemical shifts in the solid phase were calculated (B3LYP/6–31G**) for 6mpH·H2O and 6mpH2Cl, basing on the re-determined single crystal X-ray data (optimised with RHF/3-21G**).