Quantum chemical study of phenylcarbamates possessing local anaesthetic activity. Effect of hydration on stable conformations of 1-[2-(2-methoxyphenylcarbamoyloxy)ethyl]piperidine and its cation

The PCILO quantum chemical method was applied to the study of 1-[2-(2-methoxyphenylcarbamoyloxy)ethyl]piperidine (B), its cation (BH+), and hydrofluoride (BHF). For B and BH+, their principal hydration sites were established. Conformation maps of the hydrated molecules were plotted based on the “supermolecule” concept and compared with those of the isolated species. As compared to the nonhydrated molecules, the hydrated B and BH+ have a considerably smaller tendency to assume one preferred conformation. The preferred conformation of isolated molecule of BHF as obtained by the PCILO calculation agrees well with crystal structure data of the structurally related heptacaine hydrochloride.