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

Abstract

Following observations that bis(3,5-diisopropylsalicylato)diaquazinc II, [Zn II(3,5-DIPS) 2(H 2O) 2], had anti-convulsant activity, bis(acetylsalicylate)diaquazinc II, [Zn II(aspirinate) 2(H 2O) 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 II3,5-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 2O 2OO (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 2O 2O 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 2O) 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 2O) 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 2O) 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-epileptic drugs.