Enantiospecific Adsorption of Propranolol Enantiomers on Naturally Chiral Copper Surface: A Molecular Dynamics Simulation Investigation

Most of the pharmaceutical drugs are chiral and to a large extent marketed as racemates consisting of an equimolar mixture of two enantiomers.1Although enantiomers have identical structures, they exhibit differences in biological activities. In order to eliminate or reduce the unwanted enantiomer from the preparation, with the feasibility of finding an optimal therapeutical treatment, much progress in chiral separation and analysis of racemic drugs in pharmaceutical as well as clinical is highly demanding. The general scheme of enantiomeric analysis and separation is based on utility of a chiral substrate. Among many other techniques, chiral metal surfaces are widely used as enantioselective chiral heterogeneous catalysts in producing enantiomerically pure compounds. The subsequent easy separation of metal from the reaction products urges the fundamental understanding of interaction between drugs and metal surfaces. Naturally chiral metal surfaces can yield much higher enantioselectivities than minerals. Propranolol ((RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol) is a nonselective, beta-adrenergic receptor-blocking agent; it specifically competes with beta-adrenergic receptor-stimulating agents for available receptor sites.2 To examine the feasibility of enantioselective adsorption of enantiomers drugs on naturally chiral metal, we carried out MD simulation adsorption of propranolol enantiomers on chiral Cu(3,1,17)S3 and achiral Cu(100) metal surfaces. We analyzed structural and dynamical properties, as well as adsorption energetics and the molecular orientation. Investigation of enatioselective adsorption of propranolol enantiomers on naturally chiral Cu(3,1,17)S and achiral Cu(100) surfaces is quite feasible by molecular dynamic simulation. The fact that R-enantiomer binds more tightly to the Cu(3,1,17)S surface than S-enantiomer by 24.7 kJmol-1, gives the hope for an efficient and practical method useful in drug industries involving specific enantiomers. This is under the condition that drug design and advancement is highly dependent on efficient enantiomeric separation. The preferential adsorption of R-propranolol on Cu(3,1,17)S over S-propranolol may roots from specific feature of the molecule having a naphtyl part and a chain part with different tendency for adsorption characteristics of each enantiomer. According to RDF graphs and average bond lengths of propranolol atoms with Cu(3,1,17)S surface, R-propranolol adsorbs via naphtyl group while S-propranolol mainly adsorbs through atoms of chain part. Comparison of the bivarite maps confirms stronger adsorption of R-propranolol enantiomer. The difference in binding energies of propranolol enantiomers on naturally chiral Cu(3,1,17)S surface is 24.70 kJmol-1, which larger than on achiral Cu(100) surface (4.19 kJmol-1) by a factor of 6. Consequently the difference in binding of propranolol enantiomers towards Cu(3,1,17)S surface provides the feasibility of chiral discrimination process.