Thiol and H2S-Mediated NO Generation from Nitrate at Copper(II).

Reduction of nitrate is an essential, yet challenging chemical task required to manage this relatively inert oxoanion in the environment and biology. We show that thiols, ubiquitous reductants in biology, convert nitrate to nitric oxide at a Cu(II) center under mild conditions. The ß-diketiminato complex [Cl2NNF6]Cu(κ2-O2NO) engages in O-atom transfer with various thiols (RSH) to form the corresponding copper(II) nitrite [CuII](κ2-O2N) and sulfenic acid (RSOH). The copper(II) nitrite further reacts with RSH to give S-nitrosothiols RSNO and [CuII]2(µ-OH)2 en route to NO formation via [CuII]-SR intermediates. The gasotransmitter H2S also reduces nitrate at copper(II) to generate NO, providing a lens into NO3-/H2S crosstalk. The interaction of thiols with nitrate at copper(II) releases a cascade of N- and S-based signaling molecules in biology.

Electrocatalytic Ammonia Oxidation by a Low-Coordinate Copper Complex.

Molecular catalysts for ammonia oxidation to dinitrogen represent enabling components to utilize ammonia as a fuel and/or source of hydrogen. Ammonia oxidation requires not only the breaking of multiple strong N-H bonds but also controlled N-N bond formation. We report a novel ß-diketiminato copper complex [iPr2NNF6]CuI-NH3 ([CuI]-NH3 (2)) as a robust electrocatalyst for NH3 oxidation in acetonitrile under homogeneous conditions. Complex 2 operates at a moderate overpotential (η = 700 mV) with a TOFmax = 940 h-1 as determined from CV data in 1.3 M NH3-MeCN solvent. Prolonged (>5 h) controlled potential electrolysis (CPE) reveals the stability and robustness of the catalyst under electrocatalytic conditions. Detailed mechanistic investigations indicate that electrochemical oxidation of [CuI]-NH3 forms {[CuII]-NH3}+ (4), which undergoes deprotonation by excess NH3 to form reactive copper(II)-amide ([CuII]-NH2, 6) unstable toward N-N bond formation to give the dinuclear hydrazine complex [CuI]2(µ-N2H4). Electrochemical studies reveal that the diammine complex [CuI](NH3)2 (7) forms at high ammonia concentration as part of the {[CuII](NH3)2}+/[CuI](NH3)2 redox couple that is electrocatalytically inactive. DFT analysis reveals a much higher thermodynamic barrier for deprotonation of the four-coordinate {[CuII](NH3)2}+ (8) by NH3 to give the copper(II) amide [CuII](NH2)(NH3) (9) (ΔG = 31.7 kcal/mol) as compared to deprotonation of the three-coordinate {[CuII]-NH3}+ by NH3 to provide the reactive three-coordinate parent amide [CuII]-NH2 (ΔG = 18.1 kcal/mol) susceptible to N-N coupling to form [CuI]2(µ-N2H4) (ΔG = -11.8 kcal/mol).

Lewis acid-assisted reduction of nitrite to nitric and nitrous oxides via the elusive nitrite radical dianion.

Reduction of nitrite anions (NO2-) to nitric oxide (NO), nitrous oxide (N2O) and ultimately dinitrogen (N2) takes place in a variety of environments, including in the soil as part of the biogeochemical nitrogen cycle and in acidified nuclear waste. Nitrite reduction typically takes place within the coordination sphere of a redox-active transition metal. Here we show that Lewis acid coordination can substantially modify the reduction potential of this polyoxoanion to allow for its reduction under non-aqueous conditions (-0.74 V versus NHE). Detailed characterization confirms the formation of the borane-capped radical nitrite dianion (NO22-), which features a N(II) oxidation state. Protonation of the nitrite dianion results in the facile loss of nitric oxide (NO), whereas its reaction with NO results in disproportionation to nitrous oxide (N2O) and nitrite (NO2-). This system connects three redox levels in the global nitrogen cycle and provides fundamental insights into the conversion of NO2- to NO.

NO Coupling at Copper to cis-Hyponitrite: N2O Formation via Protonation and H-Atom Transfer.

Copper nitrite reductases (CuNIRs) convert NO2- to NO as well as NO to N2O under high NO flux at a mononuclear type 2 Cu center. While model complexes illustrate N-N coupling from NO that results in symmetric trans-hyponitrite [CuII]-ONNO-[CuII] complexes, we report NO assembly at a single Cu site in the presence of an external reductant Cp*2M (M = Co, Fe) to give the first copper cis-hyponitrites [Cp*2M]{[CuII](κ2-O2N2)[CuI]}. Importantly, the κ1-N-bound [CuI] fragment may be easily removed by the addition of mild Lewis bases such as CNAr or pyridine to form the spectroscopically similar anion {[CuII](κ2-O2N2)}-. The addition of electrophiles such as H+ to these anionic copper(II) cis-hyponitrites leads to N2O generation with the formation of the dicopper(II)-bis-µ-hydroxide [CuII]2(µ-OH)2. One-electron oxidation of the {[CuII](κ2-O2N2)}- core turns on H-atom transfer reactivity, enabling the oxidation of 9,10-dihydroanthracene to anthracene with concomitant formation of N2O and [CuII]2(µ-OH)2. These studies illustrate both the reductive coupling of NO at a single copper center and a way to harness the strong oxidizing power of nitric oxide via the neutral cis-hyponitrite [Cu](κ2-O2N2).

Mechanism of O-Atom Transfer from Nitrite: Nitric Oxide Release at Copper(II).

Nitric oxide (NO) is a key signaling molecule in health and disease. While nitrite acts as a reservoir of NO activity, mechanisms for NO release require further understanding. A series of electronically varied ß-diketiminatocopper(II) nitrite complexes [CuII](κ2-O2N) react with a range of electronically tuned triarylphosphines PArZ3 that release NO with the formation of O═PArZ3. Second-order rate constants are largest for electron-poor copper(II) nitrite and electron-rich phosphine pairs. Computational analysis reveals a transition-state structure energetically matched with experimentally determined activation barriers. The production of NO follows a pathway that involves nitrite isomerization at CuII from κ2-O2N to κ1-NO2 followed by O-atom transfer (OAT) to form O═PArZ3 and [CuI]-NO that releases NO upon PArZ3 binding at CuI to form [CuI]-PArZ3. These findings illustrate important mechanistic considerations involved in NO formation from nitrite via OAT.

Synthetic Metallodithiolato Ligands as Pendant Bases in [FeIFeI], [FeI[Fe(NO)]II], and [(µ-H)FeIIFeII] Complexes.

The development of ligands with specific stereo- and electrochemical requirements that are necessary for catalyst design challenges synthetic chemists in academia and industry. The crucial aza-dithiolate linker in the active site of [FeFe]-H2ase has inspired the development of synthetic analogues that utilize ligands which serve as conventional σ donors with pendant base features for H+ binding and delivery. Several MN2S2 complexes (M = Ni2+, [Fe(NO)]2+, [Co(NO)]2+, etc.) utilize these cis-dithiolates to bind low valent metals and also demonstrate the useful property of hemilability, i.e., alternate between bi- and monodentate ligation. Herein, synthetic efforts have led to the isolation and characterization of three heterotrimetallics that employ metallodithiolato ligand binding to di-iron scaffolds in three redox levels, (µ-pdt)[Fe(CO)3]2, (µ-pdt)[Fe(CO)3][(Fe(NO))II(IMe)(CO)]+, and (µ-pdt)(µ-H)[FeII(CO)2(PMe3)]2+ to generate (µ-pdt)[(FeI(CO)3][FeI(CO)2·NiN2S2] (1), (µ-pdt)[FeI(CO)3][(Fe(NO))II(IMe)(CO)]+ (2), and (µ-pdt)(µ-H)[FeII(CO)2(PMe3)][FeII(CO)(PMe3)·NiN2S2]+ (3) complexes (pdt = 1,3-propanedithiolate, IMe = 1,3-dimethylimidazole-2-ylidene, NiN2S2 = [N,N'-bis(2-mercaptidoethyl)-1,4-diazacycloheptane] nickel(II)). These complexes display efficient metallodithiolato binding to the di-iron scaffold with one thiolate-S, which allows the free unbound thiolate to potentially serve as a built-in pendant base to direct proton binding, promoting a possible Fe-H-···+H-S coupling mechanism for the electrocatalytic hydrogen evolution reaction (HER) in the presence of acids. Ligand substitution studies on 1 indicate an associative/dissociative type reaction mechanism for the replacement of the NiN2S2 ligand, providing insight into the Fe-S bond strength.

Mössbauer Spectroscopy and Theoretical Studies of Iron Bimetallic Complexes Showing Electrocatalytic Hydrogen Evolution.

Mössbauer spectroscopy and density functional theory (DFT) calculations are reported for the mononuclear Fe-nitrosyl complex [Fe( N, N'-bis(2-mercaptoethyl)-1,4-diazacycloheptane)NO] {[Fe(bme-dach)(NO)] (1)} and the series of dithiolate-bridged dinuclear complexes M-Fe(CO)Cp [M = Fe(bme-dach)(NO) (1-A), Ni(bme-dach) (2-A), and Co(bme-dach)(NO) (3-A)], in which M is a metallo-ligand to Fe(CO)Cp+ (Fe'Cp). The latter is an organometallic fragment in which Fe is coordinated by one CO and one cyclopentadienyl ligand. Complexes 1-A and 2-A were previously shown to have electrocatalytic hydrogen evolution activity. Mononuclear {Fe-NO}7 complex 1, with overall spin of 1/2, has an isomer shift of 0.23(2) mm/s [Δ EQ = 1.37(2) mm/s] and magnetic hyperfine couplings of {-38 T, -26.8 T, 8.6 T}. In complexes 2-A and 3-A, Fe'(CO)Cp+ has a diamagnetic ground state and δ = 0.33(2) mm/s (Δ EQ ≈ 1.78 mm/s), consistent with a low-spin FeII site. In contrast, in complex 1-A, M = Fe(bme-dach)(NO) (i.e., complex 1) the magnetic hyperfine interactions of both metallo-ligand, M, and low-spin Fe'Cp are perturbed and Fe'Cp exhibits small magnetic hyperfine interactions, although its isomer shift and quadrupole splittings are largely unaltered. The DFT calculations for 1-A are in agreement with the paramagnetism observed for the Fe'(CO)Cp+ iron site.

Nitrosyl Linkage Isomers: NO Coupling to N2O at a Mononuclear Site.

Linkage isomers of reduced metal-nitrosyl complexes serve as key species in nitric oxide (NO) reduction at monometallic sites to produce nitrous oxide (N2O), a potent greenhouse gas. While factors leading to extremely rare side-on nitrosyls are unclear, we describe a pair of nickel-nitrosyl linkage isomers through controlled tuning of noncovalent interactions between the nitrosyl ligands and differently encapsulated potassium cations. Furthermore, these reduced metal-nitrosyl species with N-centered spin density undergo radical coupling with free NO and provide a N-N coupled cis-hyponitrite intermediate whose protonation triggers the release of N2O. This report outlines a stepwise molecular mechanism of NO reduction to form N2O at a mononuclear metal site that provides insight into the related biological reduction of NO to N2O.

Structural and Electronic Responses to the Three Redox Levels of Fe(NO)N2 S2 -Fe(NO)2.

The nitrosylated diiron complexes, Fe2 (NO)3 , of this study are interpreted as a mono-nitrosyl Fe(NO) unit, MNIU, within an N2 S2 ligand field that serves as a metallodithiolate ligand to a dinitrosyl iron unit, DNIU. The cationic Fe(NO)N2 S2 ⋅Fe(NO)2 + complex, 1+ , of Enemark-Feltham electronic notation {Fe(NO)}7 -{Fe(NO)2 }9 , is readily obtained via myriad synthetic routes, and shown to be spin coupled and diamagnetic. Its singly and doubly reduced forms, {Fe(NO)}7 -{Fe(NO)2 }10 , 10 , and {Fe(NO)}8 -{Fe(NO)2 }10 , 1- , were isolated and characterized. While structural parameters of the DNIU are largely unaffected by redox levels, the MNIU readily responds; the neutral, S= 1 / 2 , complex, 10 , finds the extra electron density added into the DNIU affects the adjacent MNIU as seen by the decrease its Fe-N-O angle (from 171° to 149°). In contrast, addition of the second electron, now into the MNIU, returns the Fe-N-O angle to 171° in 1- . Compensating shifts in FeMNIU distances from the N2 S2 plane (from 0.518 to 0.551 to 0.851 Å) contribute to the stability of the bimetallic complex. These features are addressed by computational studies which indicate that the MNIU in 1- is a triplet-state {Fe(NO)}8 with strong spin polarization in the more linear FeNO unit. Magnetic susceptibility and parallel mode EPR results are consistent with the triplet state assignment.

Bridging cyanides from cyanoiron metalloligands to redox-active dinitrosyl iron units.

Cyanide, as an ambidentate ligand, plays a pivotal role in providing a simple diatomic building-block motif for controlled metal aggregation (M-CN-M'). Specifically, the inherent hard-soft nature of the cyanide ligand, i.e., hard-nitrogen and soft-carbon centers, is due to electronic handles for binding Lewis acids following the hard-soft acid-base principle. Studies by Holm and Karlin showed structural and electronic requirements for cyanide-bridged (por)FeIII-CN-CuII/I (por = porphyrin) molecular assemblies as biomimetics for cyanide-inhibited terminal quinol oxidases and cytochrome-C oxidase. The dinitrosyliron unit (DNIU) that exists in two redox states, {Fe(NO)2}9 and {Fe(NO)2}10, draws attention as an electronic analogy of CuII and CuI, d9 and d10, respectively. In similar controlled aggregations, L-type [(η5-C5R5)Fe(dppe)(CN)] (dppe = diphenyl phosphinoethane; R = H and Me) have been used as N-donor, µ-cyanoiron metalloligands to stabilize the DNIU in two redox states. Two bimetallic [(η5-C5R5)(dppe)FeII-CN-{Fe(NO)2}9(sIMes)][BF4] complexes, Fe-1 (R = H) and Fe*-1 (R = CH3), showed dissimilar FeIIC[triple bond, length as m-dash]N-{Fe(NO)2}9 angular bends due to the electronic donor properties of the [(η5-C5R5)Fe(dppe)(CN)] µ-cyanoiron metalloligand. A trimetallic [(η5-C5Me5)(dppe)FeII-CN]2-{Fe(NO)2}10 complex, Fe*-2, engaged two bridging µ-cyanoiron metalloligands to stabilize the {Fe(NO)2}10 unit. The lability of the FeII-CN-{Fe(NO)2}9/10 bond was probed by suitable X-type (Na+SPh-) and L-type (PMe3) ligands. Treatment of Fe-1 and Fe*-1 with PMe3 accounted for a reduction-induced substitution at the DNIU, releasing [(η5-C5R5)Fe(dppe)(CN)] and N-heterocyclic carbene, and generating (PMe3)2Fe(NO)2 as the reduced {Fe(NO)2}10 product.

Interplay of hemilability and redox activity in models of hydrogenase active sites.

The hydrogen evolution reaction, as catalyzed by two electrocatalysts [M(N2S2)·Fe(NO)2]+, [Fe-Fe]+ (M = Fe(NO)) and [Ni-Fe]+ (M = Ni) was investigated by computational chemistry. As nominal models of hydrogenase active sites, these bimetallics feature two kinds of actor ligands: Hemilabile, MN2S2 ligands and redox-active, nitrosyl ligands, whose interplay guides the H2 production mechanism. The requisite base and metal open site are masked in the resting state but revealed within the catalytic cycle by cleavage of the MS-Fe(NO)2 bond from the hemilabile metallodithiolate ligand. Introducing two electrons and two protons to [Ni-Fe]+ produces H2 from coupling a hydride temporarily stored on Fe(NO)2 (Lewis acid) and a proton accommodated on the exposed sulfur of the MN2S2 thiolate (Lewis base). This Lewis acid-base pair is initiated and preserved by disrupting the dative donation through protonation on the thiolate or reduction on the thiolate-bound metal. Either manipulation modulates the electron density of the pair to prevent it from reestablishing the dative bond. The electron-buffering nitrosyl's role is subtler as a bifunctional electron reservoir. With more nitrosyls as in [Fe-Fe]+, accumulated electronic space in the nitrosyls' π*-orbitals makes reductions easier, but redirects the protonation and reduction to sites that postpone the actuation of the hemilability. Additionally, two electrons donated from two nitrosyl-buffered irons, along with two external electrons, reduce two protons into two hydrides, from which reductive elimination generates H2.

Complexes of MN2S2·Fe(η5-C5R5)(CO) as platform for exploring cooperative heterobimetallic effects in HER electrocatalysis.

The control of aggregation at sulfur by metallodithiolates (MN2S2) has made them prime candidates as building blocks for the synthesis of biomimetics of various bimetallic enzyme active sites, with reactivity consequences implicating redox control by both metal centers. Recent studies of MN2S2 (M = Ni2+, Fe(NO)2+) bound to [(η5-C5H5)Fe(CO)]+ as electrocatalysts for proton reduction, the hydrogen evolution reaction, demonstrated reduction-induced hemi-lability of the bridging cis-dithiolates as a key step in the electrochemical proton reduction process (Ding, et al., J. Am. Chem. Soc., 2016, 138, 12920-12927). The MN2S2·Fe(η5-C5R5)(CO) platform offers numerous possibilities for tuning the electronic character of the M(µ-S2)Fe core. As well as modifying M within the metallodithiolate ligand, replacing H by CH3 at the η5-C5R5 moiety increases the electron density at the Fe center, which might facilitate the reductive Fe-S bond cleavage. Although release of a free thiolate in these hemi-labile ligands creates a needed internal pendant base, this benefit might be countered by the increase in over-potential for addition of the first electron. Herein we report the preparation and characterization of four bimetallic aggregates with the (η5-C5R5)Fe(CO) (R = H, CH3; Fe' or Fe*', respectively) or the dicarbonyl (η5-C5R5)Fe(CO)2 scaffold (R = H, CH3; Fe'' or Fe*'', respectively) bound to redox active MN2S2 ligands (M = Ni2+, Co(NO)2+; N2S2 = bismercaptoethane diazacycloheptane) Co-Fe*', Ni-Fe*', Co-Fe' and Co-Fe*'' complexes. The bidentate complexes were found to be electrocatalysts for proton reduction, although at high over-potential, especially for the derivatives of the electron-rich (η5-C5(CH3)5)Fe(CO)+. The turnover (TON) and turnover frequencies (TOF) were determined and found to be comparable to the previously reported MN2S2·Fe(η5-C5H5)(CO)+ analogues.

A matrix of heterobimetallic complexes for interrogation of hydrogen evolution reaction electrocatalysts.

Experimental and computational studies address key questions in a structure-function analysis of bioinspired electrocatalysts for the HER. Combinations of NiN2S2 or [(NO)Fe]N2S2 as donors to (η5-C5H5)Fe(CO)+ or [Fe(NO)2]+/0 generate a series of four bimetallics, gradually "softened" by increasing nitrosylation, from 0 to 3, by the non-innocent NO ligands. The nitrosylated NiFe complexes are isolated and structurally characterized in two redox levels, demonstrating required features of electrocatalysis. Computational modeling of experimental structures and likely transient intermediates that connect the electrochemical events find roles for electron delocalization by NO, as well as Fe-S bond dissociation that produce a terminal thiolate as pendant base well positioned to facilitate proton uptake and transfer. Dihydrogen formation is via proton/hydride coupling by internal S-H+···-H-Fe units of the "harder" bimetallic arrangements with more localized electron density, while softer units convert H-···H-via reductive elimination from two Fe-H deriving from the highly delocalized, doubly reduced [Fe2(NO)3]- derivative. Computational studies also account for the inactivity of a Ni2Fe complex resulting from entanglement of added H+ in a pinched -S δ-···H+··· δ-S- arrangement.

Hemilabile Bridging Thiolates as Proton Shuttles in Bioinspired H2 Production Electrocatalysts.

Synthetic analogues and computationally assisted structure-function analyses have been used to explore the features that control proton-electron and proton-hydride coupling in electrocatalysts inspired by the [NiFe]-hydrogenase active site. Of the bimetallic complexes derived from aggregation of the dithiolato complexes MN2S2 (N2S2 = bismercaptoethane diazacycloheptane; M = Ni or Fe(NO)) with (η5-C5H5)Fe(CO)+ (the Fe' component) or (η5-C5H5)Fe(CO)2+, Fe″, which yielded Ni-Fe'+, Fe-Fe'+, Ni-Fe″+, and Fe-Fe″+, respectively, both Ni-Fe'+ and Fe-Fe'+ were determined to be active electrocatalysts for H2 production in the presence of trifluoroacetic acid. Correlations of electrochemical potentials and H2 generation are consistent with calculated parameters in a predicted mechanism that delineates the order of addition of electrons and protons, the role of the redox-active, noninnocent NO ligand in electron uptake, the necessity for Fe'-S bond breaking (or the hemilability of the metallodithiolate ligand), and hydride-proton coupling routes. Although the redox active {Fe(NO)}7 moiety can accept and store an electron and subsequently a proton (forming the relatively unstable Fe-bound HNO), it cannot form a hydride as the NO shields the Fe from protonation. Successful coupling occurs from a hydride on Fe' with a proton on thiolate S and requires a propitious orientation of the H-S bond that places H+ and H- within coupling distance. This orientation and coupling barrier are redox-level dependent. While the Ni-Fe' derivative has vacant sites on both metals for hydride formation, the uptake of the required electron is more energy intensive than that in Fe-Fe' featuring the noninnocent NO ligand. The Fe'-S bond cleavage facilitated by the hemilability of thiolate to produce a terminal thiolate as a proton shuttle is a key feature in both mechanisms. The analogous Fe″-S bond cleavage on Ni-Fe″ leads to degradation.

Deciphering the photophysical role of conjugated diyne in butadiynyl fluorophores: synthesis, photophysical and theoretical study.

The present work focuses on the current interest in diyne bridged chromophores necessitating a clearer understanding of the photophysics of such molecules. The significance of the diyne moiety in the photophysics has been investigated by synthesizing simple substituted diphenyl butadiynyl derivatives following a quick and efficient microwave assisted Eglinton coupling of terminal alkynes. Emission of the fluorophores is observed from the usual locally excited (LE) state and intramolecular charge transfer (ICT) state. Separation of pure ICT emission from pure LE emission has been carried out by Gaussian/Lorentzian curve fitting. The vibronic coupling in the local transitions appears to be confined to the normal mode involving the C-C triple bond stretching of the diyne moiety. This implies that the LE transition involves the diyne moiety, a conclusion supported by quantum chemical calculations. The resolved ICT emission follows double linear dependence on ET(30) solvent polarity scale. The important role of the diyne moiety in the photophysics of this class of molecules is clearly discernible in this study.

Fluorescence-based detection of nitric oxide in aqueous and methanol media using a copper(II) complex.

The quenched fluorescent intensity of a copper(II) complex, 1, of a fluorescent ligand, in degassed methanol or aqueous (buffered at pH 7.2) solution, was found to reappear on exposure to nitric oxide. Thus, it can function as a fluorescence based nitric oxide sensor. It has been found that the present complex can be used to sense nanomolar quantities of nitric oxide in both methanol and pH 7.2 buffered-water medium.

Cobalt-catalyzed intramolecular C-N and C-O cross-coupling reactions: synthesis of benzimidazoles and benzoxazoles.

Cobalt(ii)-complex catalyzes efficiently the intramolecular C-N and C-O cross-couplings of Z-N'-(2-halophenyl)-N-phenylamidines and N-(2-bromophenyl)benzamides to afford the corresponding substituted benzimidazoles and benzoxazoles in the presence of K(2)CO(3) at moderate temperature. The protocol is general, air stable and affords the products selectively in moderate to high yield.