Axial Ligand Coordination to the C-H Amination Catalyst Rh2(esp)2: A Structural and Spectroscopic Study.

The compound Rh2(esp)2 (esp = α,α,α',α'-tetramethyl-1,3-benzenediproponoate) is the most generally effective catalyst for nitrenoid amination of C-H bonds. However, much of its fundamental coordination chemistry is unknown. In this work, we study the effects of axial ligand coordination to the catalyst Rh2(esp)2. We report here crystal structures, cyclic voltammetry, UV-vis, IR, Raman, and (1)H NMR spectra for the complexes Rh2(esp)2L2 where L = pyridine, 3-picoline, 2,6-lutidine, acetonitrile, and methanol. The compounds all show well-defined π* → σ* electronic transitions in the 16500 to 20500 cm(-1) range, and Rh-Rh stretching vibrations in the range from 304 to 322 cm(-1). Taking these data into account we find that the strength of axial ligand binding to Rh2(esp)2 increases in the series CH3OH ∼ 2,6-lutidine < CH3CN < 3-methylpyridine ∼ pyridine. Quasi-reversible Rh2(4+/5+) redox waves are only obtained when either acetonitrile or no axial ligand is present. In the presence of pyridines, irreversible oxidation waves are observed, suggesting that these ligands destabilize the Rh2 complex under oxidative conditions.

Characterization of the bridged hyponitrite complex {[Fe(OEP)](2)(µ-N(2)O(2))}: reactivity of hyponitrite complexes and biological relevance.

The detoxification of nitric oxide (NO) by bacterial NO reductase (NorBC) represents a paradigm of how NO can be detoxified anaerobically in cells. In order to elucidate the mechanism of this enzyme, model complexes provide a convenient means to assess potential reaction intermediates. In particular, there have been many proposed mechanisms that invoke the formation of a hyponitrite bridge between the heme b3 and nonheme iron (FeB) centers within the NorBC active site. However, the reactivity of bridged iron hyponitrite complexes has not been investigated much in the literature. The model complex {[Fe(OEP)]2(µ-N2O2)} offers a unique opportunity to study the electronic structure and reactivity of such a hyponitrite-bridged complex. Here we report the detailed characterization of {[Fe(OEP)]2(µ-N2O2)} using a combination of IR, nuclear resonance vibrational spectroscopy, electron paramagnetic resonance, and magnetic circular dichroism spectroscopy along with SQUID magnetometry. These results show that the ground-state electronic structure of this complex is best described as having two intermediate-spin (S = (3)/2) iron centers that are weakly antiferromagnetically coupled across the N2O2(2-) bridge. The analogous complex {[Fe(PPDME)]2(µ-N2O2)} shows overall similar properties. Finally, we report the unexpected reaction of {[Fe(OEP)]2(µ-N2O2)} in the presence and absence of 1-methylimidizole to yield [Fe(OEP)(NO)]. Density functional theory calculations are used to rationalize why {[Fe(OEP)]2(µ-N2O2)} cannot be formed directly by dimerization of [Fe(OEP)(NO)] and why only the reverse reaction is observed experimentally. These results thus provide insight into the general reactivity of hyponitrite-bridged iron complexes with general relevance for the N-N bond-forming step in NorBC.

The functional model complex [Fe2(BPMP)(OPr)(NO)2](BPh4)2 provides insight into the mechanism of flavodiiron NO reductases.

Flavodiiron nitric oxide reductases (FNORs), found in many pathogenic bacteria, are able to detoxify NO by reducing it to N2O. In this way, FNORs equip these pathogens with immunity to NO, which is a central immune defense agent in humans. Hence, FNORs are thought to promote infection of the human body, leading to chronic diseases. Despite this importance of FNORs for bacterial pathogenesis, the mechanism of NO reduction by these enzymes is not well understood. Here we present the synthesis and spectroscopic characterization of the diiron dinitrosyl model complex [Fe2(BPMP)(OPr)(NO)2](BPh4)2. The crystal structure of this complex shows two end-on-coordinated {FeNO}(7) units that, based on spectroscopic and electrochemical results, are only weakly electronically coupled. Importantly, reduction of this complex by two electrons leads to the clean formation of N2O in quantitative yield. This complex therefore represents the first example of a functional model system for FNORs. The results provide key mechanistic insight into the mechanism of FNORs and, in particular, represent strong support for the proposed "super-reduced" mechanism for these enzymes.

Structural and electronic characterization of non-heme Fe(II)-nitrosyls as biomimetic models of the Fe(B) center of bacterial nitric oxide reductase.

The detoxification of nitric oxide (NO) by bacterial NO reductase (NorBC) has gained much attention as this reaction provides a paradigm as to how NO can be detoxified anaerobically in cells. However, a clear mechanistic picture of how the heme/non-heme active site of NorBC activates NO is lacking, mostly as a result of insufficient knowledge about the properties of the non-heme iron(II)-NO adduct. Here we report the first biomimetic model complexes for this species that closely resemble the coordination environment found in the protein, using the ligands BMPA-Pr and TPA. The systematic investigation of these compounds allowed us to gain key insight into the electronic structure and geometric properties of high-spin non-heme iron(II)-NO adducts. In particular, we show how small changes in the ligand environment of iron could be used by NorBC to greatly modulate the properties, and hence, the reactivity of this species.

Density functional theory modeling of the proposed nitrite anhydrase function of hemoglobin in hypoxia sensing.

The role of NO and nitrite-bound methemoglobin (Hb(III)NO(2)(-)) in hypoxic signaling is highly controversial. One provoking possibility is that hemoglobin (Hb) functions as a nitrite anhydrase, producing N(2)O(3) (from nitrite) as an NO carrier. The ability of Hb to generate N(2)O(3) would provide an intriguing means of NO release from red blood cells. We have investigated this proposed new reactivity of Hb using density functional theory (DFT) calculations. For this purpose, models of the Hb/myoglobin (Mb) active site have been constructed. Our results show that the O-bound (nitrito) form of Hb/Mb(III)NO(2)(-) is essential for the formation of N(2)O(3). The formation and release of N(2)O(3) is shown to be energetically favorable by 1-3 kcal/mol, indicating that the anhydrase function of Hb/Mb is biologically feasible.

Iron-porphyrin NO complexes with covalently attached N-donor ligands: formation of a stable six-coordinate species in solution.

A series of substituted tetraphenylporphyrin type macrocycles (TMP or To-F(2)PP) with covalently attached N-donor ligands (pyridine or imidazole linker) have been synthesized. Linkers with varying chain lengths and designs have been applied to systematically investigate the effect of chain length and rigidity on the binding affinity of the linker to the corresponding Fe(II)-NO heme complexes. The binding of the linker is monitored in solution using a variety of spectroscopic methods including UV-vis absorption, EPR, and IR spectroscopy. Both the N-O stretching frequency and the imidazole (14)N hyperfine coupling constants show a good correlation with the Fe-(N-donor) bond strength in these systems. The complexes with covalently attached pyridyl and alkyl imidazole ligands only exhibit weak interactions of the linker with iron(II). However, the stable six-coordinate complex [Fe(To-F(2)PP-BzIM)(NO)] (4) is obtained when a rigid benzyl linker is applied. This complex exhibits typical properties of six-coordinate ferrous heme-nitrosyls in which an N-donor ligand is bound trans to NO, including the Soret band at 427 nm and the typical nine line (14)N hyperfine splitting in the EPR spectrum. A crystal structure has been obtained for the corresponding zinc complex. Here, we report the first systematic study on the requirements for the formation of stable six-coordinate ferrous heme nitrosyl complexes in solution at room temperature in the absence of excess axial N-donor ligand.

Electronic structure of six-coordinate iron(III)-porphyrin NO adducts: the elusive iron(III)-NO(radical) state and its influence on the properties of these complexes.

This paper investigates the interaction between five-coordinate ferric hemes with bound axial imidazole ligands and nitric oxide (NO). The corresponding model complex, [Fe(TPP)(MI)(NO)](BF4) (MI = 1-methylimidazole), is studied using vibrational spectroscopy coupled to normal coordinate analysis and density functional theory (DFT) calculations. In particular, nuclear resonance vibrational spectroscopy is used to identify the Fe-N(O) stretching vibration. The results reveal the usual Fe(II)-NO(+) ground state for this complex, which is characterized by strong Fe-NO and N-O bonds, with Fe-NO and N-O force constants of 3.92 and 15.18 mdyn/A, respectively. This is related to two strong pi back-bonds between Fe(II) and NO(+). The alternative ground state, low-spin Fe(III)-NO(radical) (S = 0), is then investigated. DFT calculations show that this state exists as a stable minimum at a surprisingly low energy of only approximately 1-3 kcal/mol above the Fe(II)-NO(+) ground state. In addition, the Fe(II)-NO(+) potential energy surface (PES) crosses the low-spin Fe(III)-NO(radical) energy surface at a very small elongation (only 0.05-0.1 A) of the Fe-NO bond from the equilibrium distance. This implies that ferric heme nitrosyls with the latter ground state might exist, particularly with axial thiolate (cysteinate) coordination as observed in P450-type enzymes. Importantly, the low-spin Fe(III)-NO(radical) state has very different properties than the Fe(II)-NO(+) state. Specifically, the Fe-NO and N-O bonds are distinctively weaker, showing Fe-NO and N-O force constants of only 2.26 and 13.72 mdyn/A, respectively. The PES calculations further reveal that the thermodynamic weakness of the Fe-NO bond in ferric heme nitrosyls is an intrinsic feature that relates to the properties of the high-spin Fe(III)-NO(radical) (S = 2) state that appears at low energy and is dissociative with respect to the Fe-NO bond. Altogether, release of NO from a six-coordinate ferric heme nitrosyl requires the system to pass through at least three different electronic states, a process that is remarkably complex and also unprecedented for transition-metal nitrosyls. These findings have implications not only for heme nitrosyls but also for group-8 transition-metal(III) nitrosyls in general.

Vibrational assignments of six-coordinate ferrous heme nitrosyls: new insight from nuclear resonance vibrational spectroscopy.

This Communication addresses a long-standing problem: the exact vibrational assignments of the low-energy modes of the Fe-N-O subunit in six-coordinate ferrous heme nitrosyl model complexes. This problem is addressed using nuclear resonance vibrational spectroscopy (NRVS) coupled to (15)N(18)O isotope labeling and detailed simulations of the obtained data. Two isotope-sensitive features are identified at 437 and 563 cm(-1). Normal coordinate analysis shows that the 437 cm(-1) mode corresponds to the Fe-NO stretch, whereas the 563 cm(-1) band is identified with the Fe-N-O bend. The relative NRVS intensities of these features determine the degree of vibrational mixing between the stretch and the bend. The implications of these results are discussed with respect to the trans effect of imidazole on the bound NO. In addition, a comparison to myoglobin-NO (Mb-NO) is made to determine the effect of the Mb active site pocket on the bound NO.