Correlations in hydrochloride drugs with diverse pharmacological activities. Role of N-H…Cl bonds

Abstract

In this work, the structural and vibrational properties of sixteen hydrochloride/hydrobromide drugs with different pharmacological activities have been compared and analysed in order to find some correlations among their properties and, mainly elucidate the role of N-H•••Cl bonds in them. Here, the properties of ten alkaloids: tropane, gramine, morphine, cocaine, methadone, naloxone, heroin and scopolamine as hydrochloride and hydrobromide including, the psychotropic 2-CB agent; three antihistaminic: diphenhydramine, cyclizine and promethazine and; three antihypertensive tolazoline, clonidine and guanfacine agents have been evaluated. All properties were predicted in gas phase and aqueous solution by using the hybrid B3LYP/6-31G* method and the same were evaluated in functions of their molecular weights. Here, stabilization and solvation energies, dipole moments and volumes in both media, atomic MK charges and bond N-H and N+Cl- lengths, N-H stretching modes of N-HCl bonds of hydrochloride and their cationic species and, frontier orbitals together with global electrophilicity and nucleophilicity descriptors were compared for those sixteen drugs. The results have shown that bonds N+Cl- lengths of all hydrochloride species are higher in solution, as compared with the values in gas phase. Hydrochloride species of alkaloids and antihistaminic agents in both media present higher positive MK values on the N atoms of N-HCl bonds while the species related to antihypertensive agents show higher negative MK values on the N atoms or low positive values. The species of guanfacine presents the higher number of donors and acceptors groups, higher dipole moment value in solution, low bond N-H lengths, higher negative charge on the N atom of N-HCl bond and, higher global electrophilicity index. Hydrochloride species of scopolamine and heroin present the more negative solvation energies while tolazoline the lower value. Hydrochloride species of 2-CB and diphendramine show the higher expansions volumes in solution while the species of naloxone, scopolamine and cocaine evidence volumes contractions in this medium. These studies show that the knowledge of hydration degrees, that is, the number of water molecules that hydrate the hydrochloride species are essential to understand the hydration process of these species in relation to the differences observed in solvation energies, volume variations and dipole moment values.