Theoretical in-Solution Conformational/Tautomeric Analyses for Chain Systems with Conjugated Double Bonds Involving Nitrogen(s)

Conformational/tautomeric transformations for X=CH-CH=Y structures (X = CH2, O, NH and Y = NH) have been studied in the gas phase, in dichloromethane and in aqueous solutions. The paper is a continuation of a former study where s-cis/s-trans conformational equilibria were predicted for analogues. The s-trans conformation is preferred for the present molecules in the gas phase on the basis of its lowest internal free energy as calculated at the B97D/aug-cc-pvqz and CCSD(T)CBS (coupled-cluster singles and doubles with non-iterative triples extrapolated to the complete basis set) levels. Transition state barriers are of 29-36 kJ/mol for rotations about the central C-C bonds. In solution, an s-trans form is still favored on the basis of its considerably lower internal free energy compared with the s-cis forms as calculated by IEF-PCM (integral-equation formalism of the polarizable continuum dielectric solvent model) at the theoretical levels indicated. A tetrahydrate model in the supermolecule/continuum approach helped explore the 2solute-solvent hydrogen bond pattern. The calculated transition state barrier for rotation about the C-C bond decreased to 27 kJ/mol for the tetrahydrate. Considering explicit solvent models, relative solvation free energies were calculated by means of the free energy perturbation method through Monte Carlo simulations. These calculated values differ remarkably from those by the PCM approach in aqueous solution, nonetheless the same prevalent conformation was predicted by the two methods. Aqueous solution structure-characteristics were determined by Monte Carlo. Equilibration of conformers/tautomers through water-assisted double proton-relay is discussed. This mechanism is not viable, however, in non-protic solvents where the calculated potential of mean force curve does not predict remarkable solute dimerization and subsequent favorable orientation.