Dibromine Promoted Transmetalation of an Organomercurial by Fe(CO)5: Synthesis, Properties, and Cytotoxicity of Bis(2-C6H4-2′-py-κC,N)dicarbonyliron(II)

Abstract

Bis-cyclometalated iron(II) complex [Fe(κC,N-phpy)2(CO)2] (1) (phpyH = 2-phenylpyridine) has been prepared in good yield from [Fe(CO)5] and [Hg(phpy)2] in the presence of dibromine, which is unexpectedly a crucial component of the reaction mixture. It is needed for the generation of short-lived reactive intermediate [FeBr(CO)5]Br, which is actually involved in the electrophilic substitution reaction with [Hg(phpy)2]. When irradiated by visible light, compound 1 readily affords bis(2-(pyridine-2-yl)phenyl)methanone (2) and iron oxides through the insertion of CO in the Fe–C bond of the cyclometalated moiety. Structures of iron complex 1 and ketone 2 were confirmed by X-ray crystallography. Activation of [Fe(CO)5] by Br2 represents a new approach for generating an iron intermediate, which is active in transmetalation reactions. Cytotoxic activity of 1 was tested against three gastric cancer cell lines, KATO III, AGS, and NUGC3. The activity against KATO III and NUGC3 cells is moderate, while complex 1 displayed excellent cytotoxicity against AGS cells. The molecular mechanism investigation showed that the cytotoxic activity of 1 appears independent of caspase 3 and the TP53 tumor suppressor gene, suggesting an apoptotic-independent process.