Is cocaine a social drug? Exploration of the stereo-structure of cocaine’s pharmacophore

摘要: Based on a line of evidence (logP, pKa, 1H-, and 13C-NMR, molecular modeling studies), it appears that cocaine undergoes hydrophobic collapse which may account for its unprecedented ADME properties, in particular, exceptional capacity to cross biological membranes. Using simulation techniques, the hypothesis undergone by protonated form was substantiated using semi-empirical quantum calculations (mainly AM1 PM3) performed as well ab initio (6–31 G**). A electrostatic potential map internally hydrogen-bonded structure acquired under showed continuum high electron density central part molecule around methyl ammonium two ester moieties. This picture is consistent with being locked between C=O forming strong “canonical” primary H bond weaker secondary (“non-canonical”) benzoate ester. Cocaine represents prototypical example concision because pharmacophore vector are embedded same scaffold.