Four iron(II) carbonyl complexes containing both pyridyl and halide ligands: Their synthesis, characterization, stability, and anticancer activity

Abstract

Four iron(II) carbonyl complexes, fac-[Fe (CO) 3 X 2 (py)] (X = I − , 1 and Br − , 3), fac-[{Fe (CO) 3 X 2 } 2 (bipy)] (X = I − , 2 and Br − , 4), were facilely synthesized by reacting cis-[Fe (CO) 4 X 2 ] (X = I − , Br −) with pyridine (py) and 4,4 0-dipyridine (bipy) ligands, respectively, in good yields (70%85%). These complexes were fully characterized, and the structures of Complexes 2 and 3 were crystallographically analyzed. In dimethyl sulfoxide, they decomposed rapidly to release carbon monoxide (CO), and in methanol, they showed better stability which allowed kinetically analyzing their decomposing behaviors. The selfdecomposing in methanol fitted first-order kinetics with a half-time ranging from several minutes to 1 h. Our results suggested that the ligand with great conjugation (bipy) and strong electron-donating capability (iodide) could stabilize the iron(II) carbonyl complexes. The decomposition of the iodo complexes (1 and 2) involved the production of iodine radicals. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assessments revealed that the efficacy against human bladder carcinoma cell line (RT112) is in the following trend: 1 > 2 > 3 > 4. The relatively strong efficacy of Complexes 1 and 2 is mainly contributed to the in situ generated iodine radicals. The combination of the cytotoxicity of the in situ generated radicals with the anticancer activity of CO as reported in literatures may lead to developing novel anticancer drugs with enhanced efficacy. K E Y W O R D S anticancer activity, carbon monoxide release and kinetics, iodine radical, iron carbonyl compounds, solvolysis Zhuming Guo and Jing Jin contributed equally to this work.

Further exploration of the reaction between cis‐[Fe(CO)4I2] and alkylamines: An aminium salt of fac‐[Fe(CO)3I3]− or an amine‐bound complex of fac‐[Fe(CO)3I2(NH2R)]?

“…Because this work is part of our overall effort devoted into developing CORMs based on iron carbonyl complexes, complex 1, which is of suitable stability, was also assessed for its biocompatibility, CO-releasing behaviors, and kinetics. Unlike the pyridinyl analogs we reported recently, [35] in its decomposition, no iodine radicals were detected, which rendered the complex excellent biocompatibility. [33,34,39,40] FTIR spectra were recorded on a Nicolet iS10 spectrometer.…”

“…All these distances are similar with the other octahedral iodo monoiron (II) tricarbonyls. [35,[43][44][45]…”

“…As we reported previously, the reaction between the precursor and N-containing ligands is quite tricky. Not only did the reaction produce rather different products, [34,35] but also it was found that using secondary alkylamine (HNEt 2 ) [34] and tertiary alkylamine (NEt 3 ) in the reaction failed to produce any analogs of complex 1. Instead, both amines led to the isolation of the triiodo anion, fac-[Fe (CO) 3 I 3 ] À (Section S1, Figures S6 and S7).…”

“…It is easy to prepare in that nearly quantitative yield can be achieved in the reaction of [Fe(CO) 5 ] with X 2 at ice temperature. [37] Depending on the ligands employed in the reactions, a wide range of iron carbonyl complexes or clusters could be obtained, [33][34][35]38,39] Scheme 1. In the continual efforts devoted into the mimetic chemistry of [FeFe]-hydrogenase and exploration of iron carbonyl complexes of potentials as CORMs, we have employed this precursor, cis-[Fe(CO) 4 I 2 ], to synthesize both diiron carbonyl and monoiron carbonyl complexes.…”

“…In the continual efforts devoted into the mimetic chemistry of [FeFe]-hydrogenase and exploration of iron carbonyl complexes of potentials as CORMs, we have employed this precursor, cis-[Fe(CO) 4 I 2 ], to synthesize both diiron carbonyl and monoiron carbonyl complexes. [33][34][35]39] Most recently, we attempted to prepare alkylamine bound monoiron carbonyl complexes, fac-[Fe (CO) 3 I 2 (NH 2 R)] (R = organic moieties), by reacting the diiodo precursor with alkylamines. As we reported, the reactions ended up with the same anion, fac-[Fe (CO) 3 I 3 ] À , with corresponding aminium ( + NH 3 R) as its counter ion.…”