Synthesis, crystal structure, EPR properties, and anti-convulsant activities of binuclear and mononuclear 1,10-phenanthroline and salicylate ternary copper(II) complexes

• Published in: Journal of inorganic biochemistry Vol. 89; no. 1; pp. 18 - 28
• Main Authors: Lemoine, Pascale, Viossat, Bernard, Morgant, Georges, Greenaway, Frederick T, Tomas, Alain, Dung, Nguyen-Huy, Sorenson, John R.J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.04.2002
• Subjects: 1,10-Phenanthroline; Animals; Anti-convulsant properties; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Cations, Divalent - chemistry; Central Nervous System - drug effects; Copper - chemistry; Crystal structures; Crystallography, X-Ray; Electron Spin Resonance Spectroscopy; EPR spectroscopy; Hydrogen Bonding; Magnetics; Mice; Models, Molecular; Molecular Conformation; Non-steroidal anti-inflammatory drugs; Phenanthrolines - chemical synthesis; Phenanthrolines - chemistry; Phenanthrolines - pharmacology; Rats; Salicylates - chemical synthesis; Salicylates - chemistry; Salicylates - pharmacology; Singly and dideprotonated salicylic acids; Spectrophotometry, Atomic; Structure-Activity Relationship; Ternary copper(II) complexes; 1,10-Phenanthroline; Crystal structures; Anti-convulsant properties; Singly and dideprotonated salicylic acids; Ternary copper(II) complexes; EPR spectroscopy; Non-steroidal anti-inflammatory drugs
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/S0162-0134(01)00324-5

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)-μ-bis(salicylato-O,O′)dicopper(II)] dihydrate, 1, {[Cu II 2(phen) 2(sal) 2]·2[H 2O]}, shows it to be binuclear. This dimer consists of two centrosymmetrically related pseudo-five coordinate Cu(II) atoms 3.242(2) Å 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 2O]}, 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.