The double proton transfer reaction in model formamide-formamidine dimer mimicking adenine-thymine base pair was investigated. The physical nature of the catalytic activity of the first hydration shell has been analyzed using hybrid variation-perturbation decomposition of intermolecular interaction energy. The differential transition state stabilization energy is dominated by long range electrostatic multipole term, whereas electrostatic penetration, exchange and delocalization terms are negligible or partly cancel each other. This allowed to derive (within electrostatic approximation) the generalized static and dynamic properties of the molecular environment exerting optimal catalytic activity towards canonic --> rare and rare --> canonic tautomeric rearrangement. (C) 2002 Elsevier Science B.V. All rights reserved.