Synthesis, crystal structures, and anti-convulsant activities of ternary [Zn(II)(3,5-diisopropylsalicylate)(2)], [Zn(II)(salicylate)(2)] and [Zn(II)(aspirinate)(2)] complexes

Following observations that bis(3,5-diisopropylsalicylato)diaquazinc(II), [Zn(II)(3,5-DIPS)(2)(H(2)O)(2)], had anti-convulsant activity, bis(acetylsalicylate)diaquazinc(II), [Zn(II)(aspirinate)(2)(H(2)O)(2)], and the Zn(II) ternary 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocuproine, NC) or dimethyl sulfoxide (DMSO) complexes of Zn(II)3,5-diisopropylsalicylate, salicylate, and acetylsalicylate were synthesized and spectroscopically characterized. Anti-convulsant and Rotorod toxicity activities of these complexes were determined to examine their anti-convulsant and undesirable central nervous stimulant or depressant activities of these Zn(II) non-steroidal anti-inflammatory agent complexes. Bis(3,5-diisopropylsalicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(phen)], (1) has one bidentate phen ligand and two mono-deprotonated 3,5-DIPS ligands. One of the carboxylates bonds in an asymmetric chelating mode. The Zn(II) atom exhibits a distorted bicapped rectangular pyramidal environment N(2)O(2)OO (4+1+1 *). In the neocuproine complex, bis(3,5-diisopropylsalicylato)-2,9-dimethyl-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(NC)] (2), the Zn(II) atom has a much more distorted bicapped rectangular pyramidal environment, N(2)O(2)O(2) (4+2 *), compared to 1. The two carboxylate ligands exhibit the same asymmetric coordinating mode with longer metalloelement-oxygen bond distances compared to 1. The space group of [Zn(II)(aspirinate)(2)(H(2)O)(2)] (3), which has been reported as Cc is corrected to C2/c. The zinc atom exhibits a (4+2 *) bicapped square pyramidal environment. While the two ternary phenanthroline-containing complexes, 1 and 2, evidenced weak protection against maximal electroshock (MES)- and subcutaneous Metrazol (scMET) induced seizures, [Zn(II)(3,5-DIPS)(2)(DMSO)(2)], [Zn(II)(aspirinate)(2)(H(2)O)(2)], and bis(salicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(salicylate)(2)(phen)], were found to be particularly useful in protecting against MES and scMET seizures and [Zn(II)(aspirinate)(2)(H(2)O)(2)] and [Zn(II)(salicylate)(2)(phen)] were found to have activity in protecting against Psychomotor seizures, without causing Rotorod toxicity. Activities of these and other Zn(II) complexes of non-steroidal anti-inflammatory agents are consistent with the well-known anti-inflammatory responses of Zn(II)-dependent enzymes. There was also some evidence of Rotorod toxicity consistent with a mechanism of action involving sedative-hypnotic activity of recognized anti-epilepticdrugs.