Synthesis, X-ray crystal structures and biomimetic and anticancer activities of novel copper(II)benzoate complexes incorporating 2-(4′-thiazolyl)benzimidazole (thiabendazole), 2-(2-pyridyl)benzimidazole and 1,10-phenanthroline as chelating nitrogen donor ligands

Abstract

Cu(BZA) 2(EtOH) 0.5 ( 1) was generated by the reaction of copper(II) hydroxide with benzoic acid (BZAH). [Cu(TBZH) 2(BZA)](BZA) · 0.5TBZH · H 2O ( 2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)] · 1.66EtOH ( 3) were obtained when 1 reacted with Thiabendazole (TBZH) and 2-(2-pyridyl)benzimidazole (2-PyBZIMH), respectively. [Cu(BZA) 2(phen)(H 2O)] ( 4) was isolated from the reaction of benzoic acid and 1,10-phenanthroline (phen) with copper(II)acetate dihydrate. Molecular structures of 2, 3 and 4 were determined crystallographically. 2 and 3 are hydrogen bonded dimers and trimers, respectively. The copper centres in complexes 2 and 3 are bis-chelate derivatives that have N 4O ligation and their geometry is very similar being approximately square-pyramidal. However whereas in complex 2 both TBZH ligands are neutral in 3 one of the 2-PyBZIMH chelators is deprotonated on each copper. The structural results for 4 represent a re-examination of this crystallographically known compound for which no hydrogen atom coordinates have been previously reported. It crystallises as a hydrogen bonded dimmer and is a mono-chelate of phen with each copper centre possessing N 2O 3 ligation and square pyramidal geometry. The catalase and superoxide dismutase (SOD) activities of the four complexes along with those of the known phenanthroline complexes [Cu(mal)(phen) 2] and [Cu(phendione) 3](ClO 4) 2 (malH 2 = malonic acid and phendione = 1,10-phenanthroline-5,6-dione) were investigated. Complexes 1– 4, the metal free ligands and a simple copper(II) salt were assessed for their cancer chemotherapeutic potential against the hepatocellular carcinoma (Hep-G 2) and kidney adenocarcinoma (A-498) cell lines. TBZH, 2-PyBZIMH and benzoic acid when uncoordinated to a metal centre offer poor chemotherapeutic potential. copper(II) benzoate is significantly more active than the free acid. The bis-chelate derivatives [Cu(TBZH) 2(BZA)](BZA) · 0.5TBZH · H 2O ( 2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)] · 1.66EtOH ( 3) elicit a significant cytotoxic response to the cancer cell lines tested. Replacing TBZH and 2-PyBZIMH with phen to give [Cu(BZA) 2(phen)(H 2O)] ( 4) does not significantly increase the anti-cancer activity.