On the effects of the basis set superposition error on the change of QTAIM charges in adduct formation. Application to complexes between morphine and cocaine and their main metabolites

Abstract

Eleven different complexes were found between heroin (or its main metabolite, morphine) and cocaine (or its main metabolite, ecgonine methyl ester) in a B3LYP computational study. Ten of these complexes display intermolecular hydrogen bonds, while only one is a stacked structure. All of them display positive complexation energies in the gas phase that turn into negative values in aqueous solution according to PCM calculations. Complexation energies become even more negative when explicit solvation water molecules are taken into account. Thus, complexes between these compounds could be present in biological media. The electron density of the 11 complexes was analysed within the QTAIM framework distinguishing three terms for every atomic property: (i) geometry distortion; (ii) BSSE estimated by extending the counterpoise (CP) method; and (iii) binding. We notice that: (i) geometry distortion effects are basically localised in the atoms involved in intermolecular bonds (interaction sites); (ii) counterpoise corrections for atomic properties are very small; and (iii) binding CP-corrected effects spread throughout the whole complex. The later are the most significant and indicate the important role played by hydrogens outside the interaction sites as electron density sources and sinks in complex formation.