Computational studies on electron transfer by the iminium metabolite of phencyclidine (PCP)

The iminium species have been proposed to play a role in electron transfer (ET) processes in biological systems. Iminium ions may interfere with norma l ET in the central nervous system, possibly explaining some of the physiol ogical effects of the abused drug phencyclidine (PCP). Density functional a nd semiempirical calculations were used to evaluate the potential capacity of the PCP iminium metabolite to act as an ET agent in vivo. Austin Model 1 (AMI) calculations on different possible conformations show several thermo dynamic minima, each possessing distinct minima that are similar to the pha rmacologically active structure of PCP. All structures possess negative val ues for the lowest unoccupied molecular orbital (LUMO) energies indicating the potential to act as an ET agent. The radicals produced when the iminium ions accept an electron show conformational energy profiles similar to tha t of the non-reduced species. All levels of theory show this mechanism as c hemically feasible, which suggest the intriguing possibility that ET may pl ay a role in some ET-iminium induced biological processes. (C) 2000 Elsevie r Science B.V. All rights reserved.