Bioinorganic Chemistry of the Natural [Fe(NO)₂] Motif: Evolution of a Functional Model for NO-Related Biomedical Application and Revolutionary Development of a Translational Model

Abstract

Identification of the distinctive electron paramagnetic resonance signal at g = 2.03 in the yeast cells and liver of mice treated with carcinogens opened the discovery and investigation of the natural [Fe­(NO)2] motif in the form of dinitrosyliron complexes (DNICs). In this Viewpoint, a chronological collection of the benchmark for the study of DNIC demonstrates that the preceding study of its biological synthesis, storage, transport, transformation, and function related to NO physiology inspires the biomimetic study of structural and functional models supported by thiolate ligands to provide mechanistic insight at a molecular level. During the synthetic, spectroscopic, and theoretical investigations on the structure-to-reactivity relationship within DNICs, control of the Fe–NO bonding interaction and of the delivery of NO+/•NO/HNO/NO– by the supporting ligands and nuclearity evolves into the “redesign of the natural [Fe­(NO)2] motif” as a strategy to develop DNICs for NO-related biomedical application and therapeutic approach. The revolutionary transformation of covalent a [Fe­(NO)2] motif into a translational model for hydrogenase, triggered by the discovery of redox interconversion among [{Fe­(NO)2}9-L•] ↔ {Fe­(NO)2}9 ↔ {Fe­(NO)2}10 ↔ [{Fe­(NO)2}10-L•]−, echoes the preceding research journey on [Fe]/[NiFe]-hydrogenase and completes the development of an electrodeposited-film electrode for electrocatalytic water splitting. Through the 50-year journey, bioinorganic chemistry of DNIC containing the covalent [Fe­(NO)2] motif and noninnocent/labile NO ligands highlights itself as a unique metallocofactor to join the longitudinal study between biology/chemistry/biomedical application and the lateral study toward multielectron (photo/electro)­catalysis for industrial application. This Viewpoint discloses the potential [Fe­(NO)2] motif awaiting continued contribution in order to emerge as a novel application in the next 50 years, whereas the parallel development of bioinorganic chemistry, guided by inspirational Nature, moves the science forward to the next stage in order to benefit the immediate needs for human activity.

Endogenous Conjugation of Biomimetic Dinitrosyl Iron Complex with Protein Vehicles for Oral Delivery of Nitric Oxide to Brain and Activation of Hippocampal Neurogenesis

“… 47 , 48 On the basis of the characterization of the released NO and S/Fe K-edge XAS study, a slow oxidation of the [Fe(μ-SR) 2 Fe] core within DNIC-1 under an aerobic condition initiates the transformation of bridging [HOCH 2 CH 2 S] − ligands into the released (SCH 2 CH 2 OH) 2 , which weakens the Fe-to-NO π-backbonding interaction to trigger the complete release of nitric oxide and the assembly of a ferric complex ( Scheme S1a ). 37 , 46 …”

“… 34 − 36 Inspired by natural DNIU [Fe(NO) 2 ], biomimetic study was reported to explore mononuclear {Fe(NO) 2 } 9 dinitrosyl iron complexes (DNICs) [(NO) 2 Fe(SR) 2 ] − (or [(NO) 2 Fe(L) 2 ] − ) featuring a distinctive electron paramagnetic resonance (EPR) signal at g = 2.03, which is consistent with protein-bound DNICs ( Table S1 ). 37 Moreover, interconversions among mononuclear DNICs [(NO) 2 Fe(SR) 2 ] − /[(NO) 2 Fe(SR′) 2 ] − and dinuclear DNIC [(NO) 2 Fe(μ-SR) 2 Fe(NO) 2 ] disclosed alternative mechanisms projecting on the biological delivery of DNIU [Fe(NO) 2 ]. 36 , 37 On the one hand, the transfer of DNIU [Fe(NO) 2 ] from glutathione-bound DNIC to human glutathione transferase (GST P1–1) yielding crystallographically characterized [(NO) 2 Fe(SR)(GST-Tyr7)] (SR = glutathione) unraveled the conversion of low-molecular-weight DNIC into the protein-bound form through a ligand exchange pathway.…”

“… 37 Moreover, interconversions among mononuclear DNICs [(NO) 2 Fe(SR) 2 ] − /[(NO) 2 Fe(SR′) 2 ] − and dinuclear DNIC [(NO) 2 Fe(μ-SR) 2 Fe(NO) 2 ] disclosed alternative mechanisms projecting on the biological delivery of DNIU [Fe(NO) 2 ]. 36 , 37 On the one hand, the transfer of DNIU [Fe(NO) 2 ] from glutathione-bound DNIC to human glutathione transferase (GST P1–1) yielding crystallographically characterized [(NO) 2 Fe(SR)(GST-Tyr7)] (SR = glutathione) unraveled the conversion of low-molecular-weight DNIC into the protein-bound form through a ligand exchange pathway. 38 On the other hand, the cysteine-mediated core extrusion of DNIU [Fe(NO) 2 ] from protein-bound DNIC demonstrated the reversed transformation of protein-bound DNIC into the low-molecular-weight form.…”

Dinitrosyl iron complexes: From molecular electrocatalysts to electrodeposited‐film electrodes for hydrogen evolution reaction

“…In contrast to the very weak signals of N 1s spectra of 1‐C , 3‐C , 4‐C , and 5‐C , a significant signal (400.0 eV) found in 6‐C was assigned to the residual TMEDA ligand (Figure S6). It is concluded that the major electrodeposition products derived from the extended electrolysis of 1.0 M Na 2 SO 4 aqueous solution and DNICs 1 / 3 – 6 are iron(III) oxides and the trace organic ligands on the surface of working electrodes.…”

“…In the previous investigation, the cyclic voltammetric studies of DNICs reveal two reversible one‐electron redox states associated with {Fe(NO) 2 } 9 ↔{Fe(NO) 2 } 10 ↔[{Fe(NO) 2 } 10 ‐L • ] − redox states, implicating the possibilities of DNICs to promote versatile chemical reactions associated with two‐electron HER process . Recently, we demonstrated that the {Fe(NO) 2 } 10 dinitrosyl iron complex (DNIC) [(PMDTA)Fe(NO) 2 ] (PMDTA = pentamethyldiethylene triamine) plays a significant role in triggering electrocatalytic HER in neutral 1.0 M KCl aqueous solution, through the reversible redox shuttling among {Fe(NO) 2 } 9 , {Fe(NO) 2 } 10 , and reduced‐state [{Fe(NO) 2 } 10 ] electronic states .…”