The gradient‐optimized geometry of haloperidol at the 4‐21G level

Abstract

The molecular structure of haloperidol as free base in its C(13)—C(14) trans form is optimized using Pulay's gradient method and a 4‐21G basis set without any geometrical constraints. The resulting structure is compared with the experimental structure of the free base in the C(13)—C(14) gauche form and with the experimental structure of the HBr salt of haloperidol in the C(13)—C(14) trans form. Apart from the obvious differences, the two rotameric forms of the free base show many similarities. This, together with the manner in which the differences of the two experimental structures are distributed over the haloperidol molecule, leads to the conclusion that the conspicuous differences between the experimental structures are caused by inaccuracies in the X‐ray determination of the HBr salt. Deviations of phenyl ring geometries from D6h symmetry and the asymmetry of the conformation around C(1)—C(9) could be rationalized by intramolecular effects.

Ab Initio Study of the Endohedral Complexes of C60, Si60, and Ge60with Monoatomic Ions: Influence of Electrostatic Effects and Hardness

“…The expansion shown in (1) is not exact, but two-electron integrals for which the error is unacceptably large are systematically corrected, leading to results identical to those calculated in the conventional way. Due to the appreciable gain in CPU time, this approach has afforded studies on some very large systems − in recent years.…”

Ab initio studies of crystal field effects. VII. Structure of 2,3‐diketopiperazine using a 13‐molecule cluster, a calculation involving 1092 basis functions

“…However, combining the recently introduced multiplicative integral approximation (MIA, [14]), for which the relevant equations are shortly explained in Section 2, with the direct-scF approach [15,16] introduced by Almlof et al [15], a very efficient method is obtained that allows one to study very large systems using ab initio methods. This approach allowed the complete structure optimization using gradient methods of numerous large molecules, among them the steroid, 4,4-dimethylandrostan-3-one [17], the caged hydrocarbon CZ2Hz4 [18], several conformations of the neuroleptic drug Haloperidol, 4-(4-hydroxy-4-p-chlorophenyl-piperidino)4'-fluorobutyrophenone [19], the p-lactamase inhibitor clavulanic acid [20], several dipeptides [21], and, recently, the peptides N-formyl pentaglycine and N-formyl pentaalanine [22].…”