Towards Cardiolite‐Inspired Carbon Monoxide Releasing Molecules – Reactivity of d⁴, d⁵ Rhenium and d⁶ Manganese Carb­onyl Complexes with Isocyanide Ligands

Abstract

Carbon monoxide releasing molecules (CORMs) are investigated widely in synthetic and medicinal chemistry owing to the potential therapeutic applications of the CO gas. Organometallic carbonyl complexes are best suited to play the role of CO carriers as they allow the exogenous release of CO under controlled conditions, and the toxicity of the gas can be overcome. With the long‐term goal of developing CORMs with similar properties to those of the sesta‐methoxyisobutylisonitrile (sesta‐mibi) 99mTc complex (Cardiolite), we have studied the reactivity of isocyanide ligands towards 16‐ and 17‐electron cis‐[Re(CO)2Br4]–/2– species and the [Mn(CO)5Br] complex. Six different isocyanide ancillary ligands (CNR), including mibi, were selected for this study. Their reactions with cis‐dicarbonyl ReIII and ReII complexes were accompanied by two‐ and one‐electron reduction of the metal center and resulted in the formation of stable cis‐mer‐[Re(CO)2(CNR)3Br] species, whereas the same reactions with [Mn(CO)5Br] gave fac‐[Mn(CO)3(CNR)2Br] compounds. All of the complexes were fully characterized, and single‐crystal X‐ray diffraction structure determinations were performed for selected species. In addition, unique monocarbonyl complexes were obtained from the reactions of cis‐[Re(CO)2Br4]– (1) with tert‐butyl isocyanide and cis‐[Re(CO)2Br4]2– (2) with mibi. The species, a heptacoordinate ReIII and a hexacoordinate ReII complex, respectively, were also characterized structurally. The CO‐releasing profiles, the cytotoxic effects against 3T3 fibroblast cells, and the antibacterial properties of the compounds were also investigated.

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…The ligand and complex were screened against different microbial strains (e.g., E. coli, S. aureus, L. monocytogenes and P. aeruginosa) and 16 was found~x1.5 more active than the ligand alone. A study on a series of manganese(I) tricarbonyl complexes bearing bis(2-pyridinylmethyl)(2-quinolinylmethyl)amine, bis(2-quinolinylmethyl)(2-pyridinylmethyl)amine, tris(2-quinolinylmethyl)amine, and tris(2-pyridinylmethyl)amine ligands (17, Figure 3), was reported recently by Güntzel and coworkers [58] [59]. Several other manganese metal complexes have been recently tested for their antimicrobial efficacy but were not found to be active [60][61][62][63].…”

A Rhenium Isonitrile Complex Induces Unfolded Protein Response‐Mediated Apoptosis in Cancer Cells

“…In this context, our group has been exploring the anticancer activity of polypyridyl rhenium(I) tricarbonyl complexes . Certain members of this class of compounds exhibit potent cytotoxic activity, which can be leveraged for their use as anticancer agents . Here, we describe our investigation of a new rhenium(I) tricarbonyl complex bearing a chelating polypyridyl ligand and an axial isonitrile ligand as a potent anticancer agent.…”

“…[12][13][14][15] Certain members of this class of compounds exhibit potent cytotoxic activity,w hich can be leveragedf or their use as anticancer agents. [16][17][18][19][20][21][22][23] Here, we describe our investigation of an ew rhenium(I) tricarbonyl complexb earing ac helating polypyridyl liganda nd an axial isonitrile ligand as ap otent anticancer agent.O ur efforts to understand the mechanismo f actiono ft his tricarbonyl rhenium isonitrile polypyridyl (TRIP) complex ( Figure 1) have revealed that it is an effective ER stress-inducing agent with significant antiproliferativeactivity. TRIP was synthesized by treating the previously reported complex [Re(CO) 3 (dmphen)OTf] with excess para-tolyl isonitrile in tetrahydrofuran.…”

CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy

“…As abovementioned, the spectroscopic nature of MCCs confirms the identification and recognition of significant trace elements like ruthenium [73,74], manganese [49,74,75,76,77,78], iron [37,79], cobalt [80,81], tungsten [82], osmium [83], molybdenum [82] and rhenium [84]. The developed organometallic carbonyl complexes CORMs are CORM-1, CORM-2, CORM-3, CORM-401, ALF492, CORM-A1, B 12 -ReCORM-2, Re-CORM-1, CORMA-1-PLA and ALF186.…”