Interaction of anticonvulsant drugs with metals: a semi-empirical molecular orbital study of phenytoin-zinc(II) complexation

The interaction of Zn(II) cation with the anticonvulsant phenytoin (PHT) wa s investigated using semi-empirical AM1 molecular orbital calculations. All possible modes of PHT-Zn(II) complexation were systematically studied by a ligning Zn(II) along the three amide faces of PHT's imidazoline-2,4-dione r ing. The AM1 calculations indicated that Zn(II) bridges two PHT molecules; six Zn(PHT)(2)(2+) complexes were evaluated. In more stable structures, Zn( II) coordinates with two PHT through amide oxygens. These structures were h ydrated, further optimized, and evaluated. (C) 1999 Elsevier Science B.V. A ll rights reserved.