Continuum solvent effects on various isomers of bilirubin

Abstract

The interconversion of the two “ridge-tile” forms (M and P) of bilirubin, modelled without methyl group substitutions on the heteroaromatic rings, is considered in the gas-phase and in aqueous solution employing the polarizable continuum model (PCM) of the solvent, to elucidate the toxic pigment peculiar solubility features. Single point HF/6-31G* calculations were carried out in acuo and in solution on a few structures along the interconversion path, obtained ia a molecular mechanics (MM) systematic conformational search, MM energy refinement and ab initio HF/3-21G energy minimisation. In order to determine under which form bilirubin is excreted, the stability and the solvation properties displayed by normal (ZZ) bilirubin were compared to those of isomers obtainable by photoirradiation. A few products of the Z→E photoisomerisation were thus model built starting from the ZZ conformers and optimised at the HF/3-21G level. Moreover HF/6-31G* geometry optimisations were carried out on a few selected conformers and the solvent effect was evaluated with PCM at the same level. Møller–Plesset second order correlation corrections, included in the gas phase calculations, stabilised the minimum energy structure with respect to the saddle point of the M–P interconversion potential energy surface. All the results obtained for the isomer conformations here considered, which turned out to be fairly similar to the HF/6-31G*//HF/3-21G ones, in summary, did not show a preferential solvation for the E forms at the ground state. Preliminary calculations on a very small model system might suggest that bilirubin is solvated at the excited state.