Manganese(I) tricarbonyl complexes: UV-dependent antioxidant activity, electrochemistry, and DFT/TDDFT calculation

<p>As important catalysts, metal carbonyl complexes have received considerable attention in recent years owing to their ability to store and transport carbon monoxide that have been proven to function as antiinflammatory, antiapoptotic, and antiproliferative agents. In addition, imidazole/benzimidazole derivative molecules have been known to be bioactive owing to their antihypertensive, antiinflammatory, and antimicrobial properties. Combining these two bioactive species could be a good idea for possible synergistic effect. In this study, [Mn(CO)₃(bpy)L]X (bpy =2,2-bipyridyl; X = PF₆, SO₃CF₃, L = imidazole, N-methylimidazole, benzimidazole, N-benzylbenzimidazole, N-4-chlorobenzylbenzimidazole) complexes have been characterized electrochemically and related to CO-releasing properties. The molecules have been theoretically analyzed in terms of electronic transitions and spin-density plot in water, acetonitrile, and gas phase for having insight that promote CO-releasing and electroactivity characteristics. Antioxidant activity of the complexes has also been analyzed in order to gain a possible relationship with CO-releasing properties of the complexes.</p

CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands

<p>Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the pathogenesis of cancer. CO is produced by enzymatic degradation of heme in mammals. Heme oxygenase 1 (HO-1) catalyzes the breakdown of heme into CO, ferrous iron, and biliverdin. CO induces HO-1 and inhibits cell proliferation. Cancer cells exposed to several stress factors (hypoxia, reactive oxygen species, cis-platin, and oxidative stress), and HO-1 displays cytoprotective role against oxidative stress and inhibits apoptosis, metastases, angiogenesis, and cell proliferation processes. Therefore, metal containing CO-releasing molecules (CORMs) have been designed as an effective cancer treatment strategy. CORMs are responsible for releasing controlled amounts of CO to cells and tissues. Thus, we synthesized [Mn(CO)₃(bpy)L]X manganese containing CORMs [bpy = 2,2′-bipyridine, X = hexafluorophosphate (PF₆), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. <i>In vitro</i> experiments indicated that the compounds inhibited cell proliferation and exhibited cytotoxic effect on breast cancer cells. Moreover, side groups of the compounds enhanced the anticancer effects in MCF-7 cell line. These manganese containing CORMs gave promising results and may be used as a drug template for effective treatment of invasive ductal breast carcinoma.</p