Synthesis, crystal structure, EPR properties, and anti-convulsant activities of binuclear and mononuclear 1,10-phenanthroline and salicylate ternary copper(II) complexes.
Two ternary Cu(II) complexes of 1,10-phenanthroline (phen) and singly (Hsal(-)) or dideprotonated (sal(2-)) salicylate ligands were synthesized, their X-ray crystal structure and electron paramagnetic resonance spectral characteristics determined, and evaluated for anti-convulsant activities in the maximal electroshock (MES) and Metrazol models of seizure and Rotorod toxicity. The X-ray crystal structure of [bis(1,10-phenanthroline)-mu-bis(salicylato-O,O')dicopper(II)] dihydrate, 1, ([Cu(II)(2)(phen)(2)(sal)(2)].2[H(2)O]), shows it to be binuclear. This dimer consists of two centrosymmetrically related pseudo-five coordinate Cu(II) atoms 3.242(2) A apart and bridged by two dideprotonated salicylate ligands. The X-ray crystal structure of [bis(1,10-phenanthroline)(salicylato)copper(II)][salicylate] monohydrate, 2, ([Cu(II)(phen)(2)(Hsal)](+)[Hsal](-)[H(2)O]), shows it to be mononuclear. This complex cation exhibits a highly irregular distorted square pyramidal geometry about the Cu(II) atom, (4+1+1*). Each salicylate is singly deprotonated and one of them is ligand bonded in an asymmetric chelating mode. EPR results for 2 indicate that in concentrated DMF solution phen remains bonded to copper but salicylate is likely monodentate in contrast to the situation for 1. However, in dilute DMF solution, both 1 and 2 form the same species, which accounts for the similarity in anti-convulsant activity of the two compounds. Both 1 and 2 were found to be effective in preventing MES-induced seizures and ineffective in preventing Metrazol-induced seizures. Rotorod toxicity, consistent with central nervous system depression, paralleled the observed anti-convulsant activity. It is suggested that the observed anti-convulsant activity is consistent with central nervous system depression as a physiological mechanism in overcoming MES-induced seizures due to MES-induced brain inflammatory disease.
Lemoine
Pascale
P
Laboratoire de Cristallographie et de Résonance Magnétique Nucléaire Biologiques UMR 8015, Faculté de Pharmacie Paris V, 75006, Paris, France.
Viossat
Bernard
B
Morgant
Georges
G
Greenaway
Frederick T
FT
Tomas
Alain
A
Dung
Nguyen Huy
NH
Sorenson
John R J
JR
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002413:Cations, Divalent / Q000737:chemistry; D002490:Central Nervous System / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D006860:Hydrogen Bonding; D008280:Magnetics; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D002413:Cations, Divalent; D010618:Phenanthrolines; D012459:Salicylates; D003300:Copper; C025205:1,10-phenanthroline