Solvent-mediated tautomerization of purine: single to quadruple proton transfer

We present calculations for the structures and the tautomerization reaction of purine and purine – (H₂O)_n (n=1–3) clusters. We find two pathways (via the carbene and the sp³-type intermediate) for the 9 ↔ 7 tautomerization of bare purine. The barrier heights for the 9 → 3 and 9 → 7 tautomerization of bare purine are calculated to be large (60–70 kcal/mol). Hydrogen bonding with the water molecule(s), however, dramatically lowers the 9 → 3 barrier by the concerted multiple proton transfer mechanism, favoring the formation of the conformer 3(H)- relative to the 7(H)-purine in the microsolvated environment, in contrast to the gas phase or the aqueous solution.