The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

Abstract

Nitric oxide (NO) is an important signaling molecule that is involved in a wide range of physiological and pathological events in biology. Metal coordination chemistry, especially with iron, is at the heart of many biological transformations involving NO. A series of heme proteins, nitric oxide synthases (NOS), soluble guanylate cyclase (sGC), and nitrophorins, are responsible for the biosynthesis, sensing, and transport of NO. Alternatively, NO can be generated from nitrite by heme- and copper-containing nitrite reductases (NIRs). The NO-bearing small molecules such as nitrosothiols and dinitrosyl iron complexes (DNICs) can serve as an alternative vehicle for NO storage and transport. Once NO is formed, the rich reaction chemistry of NO leads to a wide variety of biological activities including reduction of NO by heme or non-heme iron-containing NO reductases and protein post-translational modifications by DNICs. Much of our understanding of the reactivity of metal sites in biology with NO and the mechanisms of these transformations has come from the elucidation of the geometric and electronic structures and chemical reactivity of synthetic model systems, in synergy with biochemical and biophysical studies on the relevant proteins themselves. This review focuses on recent advancements from studies on proteins and model complexes that not only have improved our understanding of the biological roles of NO but also have provided foundations for biomedical research and for bio-inspired catalyst design in energy science.

A Copper(II)‐Nitrite Complex Hydrogen‐Bonded to a Protonated Amine in the Second‐Coordination‐Sphere

“…[7] It is noteworthy that the proposed reaction mechanisms for Fe/Cu mediated NiR activities suggest the participation of a Fe/Cu-(HONO) species (Figure 1). [8,9] Moreover, the heme-ferrous site of deoxy-hemoglobin (deoxy-Hb) reduces NO 2 À and affords nitrosyl-Hb through the involvement of an Fe-bound nitrous acid species. [4,10] The intermediacy of a heme-Fe-(HONO) species has also been proposed in the reductive nitrosylation of methemoglobin.…”

Simultaneous binding of heme and Cu with amyloid β peptides: active site and reactivities

“…Although all the Aβ bound complexes can perform reduction of nitrite to NO akin to naturally occurring nitrite reductases, 64,[74][75][76][77][78][79] there is a significant difference in the rate of nitrite reduction between heme(III)-Cu(I)-Aβ and the other metal/cofactor bound Aβ complexes. The rates of nitrite reduction for heme(III)-Cu(I)-Aβ, heme(II)-Cu(I)-Aβ, heme(II)-Aβ and Cu(I)-Aβ are 0.17, 0.04, 0.03 and 0.05 min −1 , respectively.…”

Triphenylmethyl Thionitrite: An Efficient NO Transfer Reagent During the Synthesis of a Triruthenium Nitrosyl Cluster

“…Some time ago we successfully controlled the stoichiometry by the use of N ‐methyl‐ N ‐nitroso‐ p ‐toluene‐sulfonamide (diazald) for the synthesis of diruthenium complexes bearing bridging nitrosyl ligands [3] . Therein, we examined a related NO transfer agent by the use of triphenylmethyl thionitrite (TTN) for preparing nitrosyl complexes as already described in the literature [4–8] . Moreover, S ‐nitrosothiols play an important role in mediating the chemistry of the NO molecule in biochemical processes [7,8] .…”

“…[4][5][6][7][8] Moreover, S-nitrosothiols play an important role in mediating the chemistry of the NO molecule in biochemical processes. [7,8] For introducing the NO ligand in the triruthenium metal core of 1 in a clean way, we investigated the reaction of the latter with triphenylmethyl thionitrite (Ph 3 CSNO).…”

“…[3] Therein, we examined a related NO transfer agent by the use of triphenylmethyl thionitrite (TTN) for preparing nitrosyl complexes as already described in the literature. [4][5][6][7][8] Moreover, S-nitrosothiols play an important role in mediating the chemistry of the NO molecule in biochemical processes. [7,8] For introducing the NO ligand in the triruthenium metal core of 1 in a clean way, we investigated the reaction of the latter with triphenylmethyl thionitrite (Ph 3 CSNO).…”