Dimethylsulfoxide (
DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have
anticonvulsant activity, the new ternary complex was also examined for
anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for
zinc complex mediated
anticonvulsant activity. Dissolving the structurally unknown complex in
DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate
ligands and two bonded
DMSO ligands,
Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each
DMSO ligates via its
sulfoxide O atom while each 3,5-diisopropylsalicylate
ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same
ligand. Both 3,5-DIPS
acid and
Zn(II)(3,5-DIPS)2(DMSO)2 were examined for
anticonvulsant activity in the Maximal Electroshock (MES) and
Metrazol (MET) models of
seizures and found to prevent both types of
seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free
ligand. The influence of a Zn 3,5-DIPS complex and of the
ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of
anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized
Zymosan was observed, and the Zn complex was significantly more effective than the free
ligand. It is concluded that mononuclear Zn complexes have
anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of
superoxide or down-regulation of
Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.