Modeling of tautomerism of pyridine-2(1H)-thione from vapor to solution†

Abstract

Using the well-characterized pyridine-2(1H)-thione (1)/pyridine-2-thiol (2) system as a model of thiated nucleobases in DNA or RNA, ab initio (HF, MP2 and MP4) and density functional theory (B3LYP) methods using large basis sets were applied to reproduce structures and tautomerization free energies. Hydrogen bonds of the dimerized thione 1 in the solid state were well-reproduced by the B3LYP method. Electronic correlation similarly stabilized both 1 and 2 protomers, and so the gas-phase free energy of the 1/2 equilibrium was equally overestimated by 4 kJ mol^–1 in favour of the 2 by HF, MP2(full) or MP4(SDTQ)/6-311+G(2d,p) ab initio methods. Otherwise, the B3LYP method systematically overestimated the relative stability of 1, but using the 6-311+G(2d,p) basis set, the error was comparable to ab initio methods. Dunning’s D95+(2d,p) and Aug-cc-pVDZ basis sets gave worse protomeric free energies than Pople’s basis sets using the B3LYP method. The nonspecific solvent effect on 1/2 protomerization was accurately predicted (within 2 kJ mol^–1) by the SCIPCM self-consistent reaction field (SCRF) methodology at the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) level of theory. The Onsager SCRF method or HF theoretical treatment of the solvent effects gave less good results.