In the work described below, the HOMO energies of several tricyclic antidepressants and neuroleptics were calculated with 3 different methods, referred to as the RHF, LSD, and SE-AM1 methods. The drugs studied were promazine, chlorprothixene, chlorpromazine, dibenzepine, amitriptyline, imipramine, clomipramine and opipramol. These eight drugs have a phenothiazine-like structure in common.
When the HOMO energies of these 8 drugs were calculated using the RHF method, all values were between 7.4-8.87 electron volts (eV). HOMO values for these drugs ranged from 7.36-8.34 eV using the SE-AM1 method. These HOMO energies, obtained theoretically, are similar to the ionization energies of phenothiazine drugs obtained experimentally with photoelectron spectroscopy.
Most of the drugs studied have Nitrogen or Sulfur on the main ring. Out of this series of 8, promazine consistently had the smallest absolute value for HOMO energy.
“The contribution to the HOMO and LUMO from the atomic orbitals of the Nitrogen in the central ring is remarkable.” (J.A. Cogordan, 1999)
Reference
Cogordan J. A., M. Mayoral, E. Angeles, R. A. Toscano and R. Martinez. (1999). Neuroleptic and antidepressant tricyclic compounds: Theoretical study for predicting their biological activity by semiempirical, density functional, and hartree-fock methods. Int J Quant Chem. 71, 415-432.
