Coordination Chemistry of Nitric Oxide and Biological Signaling

Abstract

Nitric Oxide (NO) is a key intermediate in the nitrogen redox cycles that operate in soils, water and biological fluids, affording reversible interconversions between nitrates to ammonia and vice-versa. The discovery of its biosynthesis in mammals for signaling purposes generated a research explosion on the ongoing chemistry occurring in specific cellular compartments, centered on NO reactivity toward O2, thiols, amines, and transition metals, as well as derivatives thereof. The present review deals with the coordination chemistry of NO toward selected iron and ruthenium centers. We place specific attention to the three redox states of the nitrosyl group: NO+, NO and NO–/HNO, describing changes in structure and reactivity as coordination takes place. Noteworthy are the results with the most reduced nitroxyl-species that allow establishing the changes in the measurable pKa values for the HNO-bound complexes, also revealing the abrupt decrease in reducing power and trans-releasing abilities of the protonated species over the unprotonated ones, NO–. Comparative results using non-heme and heme proteins and models prove useful for suggesting further improvements in the current research status of complex enzymatic behavior.

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

“…The first NO complex was reported by Playfair in 1849, sodium nitroprusside (SNP), Na 2 [Fe­(CN) 5 (NO)], which was prepared by the reaction of K 4 [Fe­(CN) 6 ] with nitric acid and obtained as an orange-red solid . The crystal structure of this compound shows discrete [Fe­(CN) 5 (NO)] 2– octahedra with linear FeNO units (see Figure ) and unexpectedly short Fe–NO bond lengths of 1.63 Å, which is actually similar to the Fe–O distances typically observed in high-valent Fe­(IV)=O intermediates. , This indicates the presence of a very strong Fe–NO bond in SNP, which is further corroborated by the Fe–NO stretch of this complex of 652 cm –1 (Fe–NO force constant: 4.05 mdyn/Å) .…”

“…A similar situation is encountered for the ls-{FeNO} 6−8 complexes in hemes, as exemplified by corresponding model complexes and NO adducts in many different proteins, , and a corresponding tetracarbene analog . Scientists were able to obtain nitroprusside in both the ls-{FeNO} 6 and the ls-{FeNO} 7 state, and a further one-electron reduced form was obtained as well, which was initially thought to be the analogous, six-coordinate (6C) ls-{FeNHO} 8 , or Fe­(II)–NHO, species with N-bound HNO. ,, However, a subsequent computational study pointed out that the putative ls-{FeNO} 8 complex, [Fe­(CN) 5 (NO)] 4– , is susceptible to cyanide release. Loss of cyanide would create a five-coordinate (5C), square-pyramidal HNO complex, [Fe­(CN) 4 (NHO)] 2– , and lead to a more complicated speciation in solution than initially envisioned.…”

“…), as illustrated in Scheme . This process is generally referred to as “reductive nitrosylation” or “autoreduction”, which, in the presence of excess NO, leads to the formation of the corresponding ferrous heme–nitrosyl complex. ,, The electrophilic reactivity of the coordinated NO + ligand in ls-{FeNO} complexes has been studied in much detail for nitroprusside, as reviewed in refs , , , and . The autoreduction process shows pseudo-first order kinetics with respect to the concentration of the ferric heme–nitrosyl complex, where excess NO formally acts as the reductant .…”

“…For [Ru­(Me 3 [9]­aneN 3 )­(bpy)­(NO)] 3+/2+/+ , Slep and coworkers prepared the whole ls-{RuNO} 6−8 series and the corresponding HNO complex, ls-{RuNHO} 8 , and the pK A of the bound HNO ligand was determined (9.78) in water. , For sodium nitroprusside, the ls-{FeNHO} 8 complex could be obtained as well, with a pK a of 7.7 . However, in this case the nature of the reduced complex is unclear . In the original publication, the HNO complex was proposed to be 6C, [Fe­(CN) 5 (NHO)] 3– , but following computational studies indicate that the ls-{FeNHO} 8 complex is actually 5C .…”

“…Despite the fact that SNP and the above-mentioned ruthenium-pentammine nitrosyls are completely unrelated complexes, it is striking how similar the structural and spectroscopic properties of their M–NO units are (M = transition metal). From early days on, the strong, linear Fe–NO bond in SNP combined with the many analogies of CO and NO complexes were seen as evidence for the NO ligand having distinct nitrosonium (NO + ; isoelectronic with CO; see Figure ) character in nitroprusside, − and the same applies to the ruthenium-pentammine nitrosyl complexes. , In accordance with this electronic structure description, the coordinated NO + ligand in these complexes is electrophilic, and reactive towards many different types of nucleophiles. ,,− These examples illustrate the many challenges that scientists are facing in pinpointing the correct electronic structures of various transition-metal NO compounds. This is further illustrative of NO’s behavior as a non-innocent ligand and highlights the fact that transition-metal–NO bonds are often highly covalent.…”