A Metal Complex Incorporating Some Drug Molecules as Ligands

Thirteen years ago, without any pharmacological interests particularly, we have reported on preparations, electronic and crystal structures of a copper(II) complexes having 5,5-diphenylhydantoinate (phenytoinate; deprotonated phenytoin) and 2-phenylethylamine (phenethylamine) ligands (Figure 1) [1]. Before this paper, I (mainly supervised by the late Dr. Seiko Komorita at Osaka university, Japan) have systematically studied on copper(II) complexes of phenytoinate ligands [2-6]. These complexes afford various coordination geometries in the crystalline states by slight changes of steric hindrance or other structural features accompanying with changes of electronic sates (optical properties). For example, four-coordinated square planar [CuN4] (reddish violet color) [1,4-6], distorted square planar [CuN4] (blue violet color) [3,4], and five-coordinated square pyramidal [CuN4O] (blue color) coordination environments were typically determined and found by X-ray crystallography. As for phenytoin or the related organic compounds of 5-substitued hydantoin derivatives and common imides such as succinimide, phthalimide, maleimide and so on, it should be noted that deprotonated nitrogen coordination atoms have pi-orbitals distributing perpendicular to the five-membered hydantoin ring, which resulted in formation of in ([CuN4]) plane pi-character of coordination bonds according to Komorita’s studies. Such circumstance may be characteristic to monodentate ligands of deprotonated hydantoin derivatives. In contrast, phenethylamine binds to copper(II) ion through amino group.