Metal-Tuned Ligand Reactivity Enables CX2 (X = O, S) Homocoupling with Spectator Cu Centers.

Ligand non-innocence is ubiquitous in catalysis with ligands in synthetic complexes contributing as electron reservoirs or co-sites for substrate activation. The latter chemical non-innocence is manifested in H+ storage or relay at sites beyond the metal primary coordination sphere. Reaction of a competent CO2-to-oxalate reduction catalyst, namely, [K(THF)3](Cu3SL), where L3- is a tris(ß-diketiminate) cyclophane, with CS2 affords tetrathiooxalate at long reaction times or at high CS2 concentrations, where otherwise an equilibrium is established between the starting species and a complex-CS2 adduct in which the CS2 is bound to the C atom on the ligand backbone. X-ray diffraction analysis of this adduct reveals no apparent metal participation, suggesting an entirely ligand-based reaction controlled by the charge state of the cluster. Thermodynamic parameters for the formation of the aforementioned Cligand-CS2 bond were experimentally determined, and trends with cation Lewis acidity were studied, where more acidic cations shift the equilibrium toward the adduct. Relevance of such an adduct in the reduction of CO2 to oxalate by this complex is supported by DFT studies, similar effects of countercation Lewis acidity on product formation, and the homocoupled heterocumulene product speciation as determined by isotopic labeling studies. Taken together, this system extends chemical non-innocence beyond H+ to effect catalytic transformations involving C-C bond formation and represents the rarest example of metal-ligand cooperativity, that is, spectator metal ion(s) and the ligand as the reaction center.

Metal Site-Specific Electrostatic Field Effects on a Tricopper(I) Cluster Probed by Resonant Diffraction Anomalous Fine Structure (DAFS).

Studies of multinuclear metal complexes are greatly enhanced by resonant diffraction measurements, which probe X-ray absorption profiles of crystallographically independent metal sites within a cluster. In particular, X-ray diffraction anomalous fine structure (DAFS) analysis provides data that can be interpreted akin to site-specific XANES, allowing for differences in metal K-edge resonances to be deconvoluted even for different metal sites within a homometallic system. Despite the prevalence of Cu-containing clusters in biology and energy science, DAFS has yet to be used to analyze multicopper complexes of any type until now. Here, we report an evaluation of trends using a series of strategically chosen Cu(I) and Cu(II) complexes to determine how energy dependencies of anomalous scattering factors are impacted by coordination geometry, ligand shell, cluster nuclearity, and oxidation state. This calibration data is used to analyze a formally tricopper(I) complex that was found by DAFS to be site-differentiated due to the unsymmetrical influence on different Cu sites of the electrostatic field from a proximal K+ cation.

Partial Deoxygenative CO Homocoupling by a Diiron Complex.

One route to address climate change is converting carbon dioxide to synthetic carbon-neutral fuels. Whereas carbon dioxide to CO conversion has precedent in homo- and heterogeneous catalysis, deoxygenative coupling of CO to products with C-C bonds-as in liquid fuels-remains challenging. Here, we report coupling of two CO molecules by a diiron complex. Reduction of Fe2 (CO)2 L (2), where L2- is a bis(ß-diketiminate) cyclophane, gives [K(THF)5 ][Fe2 (CO)2 L] (3), which undergoes silylation to Fe2 (CO)(COSiMe3 )L (4). Subsequent C-OSiMe3 bond cleavage and C=C bond formation occurs upon reduction of 4, yielding Fe2 (µ-CCO)L. CO derived ligands in this series mediate weak exchange interactions with the ketenylidene affording the smallest J value, with changes to local metal ion spin states and coupling schemes (ferro- vs. antiferromagnetism) based on DFT calculations, Mössbauer and EPR spectroscopy. Finally, reaction of 5 with KEt3 BH or methanol releases the C2 O2- ligand with retention of the diiron core.

Dinitrogen Coordination to a High-Spin Diiron(I/II) Species.

Dinitrogen coordination to iron centers underpins industrial and biological fixation in the Haber-Bosch process and by the FeM cofactors in the nitrogenase enzymes. The latter employ local high-spin metal centers; however, iron-dinitrogen coordination chemistry remains dominated by low-valent states, contrasting the enzyme systems. Here, we report a high-spin mixed-valent cis-(µ-1,2-dinitrogen)diiron(I/II) complex [(FeBr)2 (µ-N2 )Lbis ]- (2), where [Lbis ]- is a bis(ß-diketiminate) cyclophane. Field-applied Mössbauer spectra, dc and ac magnetic susceptibility measurements, and computational methods support a delocalized S=7 /2 Fe2 N2 unit with D=-5.23 cm-1 and consequent slow magnetic relaxation.

Access to Metal Centers and Fluxional Hydride Coordination Integral for CO2 Insertion into [Fe3(µ-H)3]3+ Clusters.

CO2 insertion into tri(µ-hydrido)triiron(II) clusters ligated by a tris(ß-diketiminate) cyclophane is demonstrated to be balanced by sterics for CO2 approach and hydride accessibility. Time-resolved NMR and UV-vis spectra for this reaction for a complex in which methoxy groups border the pocket of the hydride donor (Fe3H3L2, 4) result in a decreased activation barrier and increased kinetic isotope effect consistent with the reduced sterics. For the ethyl congener Fe3H3L1 (2), no correlation is found between rate and reaction solvent or added Lewis acids, implying CO2 coordination to an Fe center in the mechanism. The estimated hydricity (50 kcal/mol) based on observed H/D exchange with BD3 requires Fe-O bond formation in the product to offset an endergonic CO2 insertion. µ3-hydride coordination is noted to lower the activation barrier for the first CO2 insertion event in DFT calculations.

Dinitrogen Insertion and Cleavage by a Metal-Metal Bonded Tricobalt(I) Cluster.

Reduction of a tricobalt(II) tri(bromide) cluster supported by a tris(ß-diketiminate) cyclophane results in halide loss, ligand compression, and metal-metal bond formation to yield a 48-electron CoI3 cluster, Co3LEt/Me (2). Upon reaction of 2 with dinitrogen, all metal-metal bonds are broken, steric conflicts are relaxed, and dinitrogen is incorporated within the internal cavity to yield a formally (µ3-η1:η2:η1-dinitrogen)tricobalt(I) complex, 3. Broken symmetry DFT calculations (PBE0/def2-tzvp/D3) support an N-N bond order of 2.1 in the bound N2 with the calculated N-N stretching frequency (1743 cm-1) comparable to the experimental value (1752 cm-1). Reduction of 3 under Ar in the presence of Me3SiBr results in N2 scission with tris(trimethylsilyl)amine afforded in good yield.

Cleavage of cluster iron-sulfide bonds in cyclophane-coordinated FenSm complexes.

Reaction of the tri(µ-sulfido)triiron(iii) tris(ß-diketiminate) cyclophane complex, Fe3S3LEt/Me (1), or of the di(µ-sulfido)diiron(iii) complex Fe2S2HLEt/Me (5), with the related tri(bromide)triiron(ii) complex Fe3Br3LEt/Me (2) results in electron and ligand redistribution to yield the mixed-ligand multiiron complexes, including Fe3Br2SLEt/Me (3) and Fe2Br2SHLEt/Me (4). The cleavage and redistribution observed in these complexes is reminiscent of necessary Fe-S bond cleavage for substrate activation in nitrogenase enzymes, and provides a new perspective on the lability of Fe-S bonds in FeS clusters.

Evaluating Metal Ion Identity on Catalytic Silylation of Dinitrogen Using a Series of Trimetallic Complexes.

We report catalytic silylation of dinitrogen to tris(trimethylsilyl)amine by a series of trinuclear first row transition metal complexes (M = Cr, Mn, Fe, Co, Ni) housed in our tris(ß-diketiminate) cyclophane (L 3- ). Yields are expectedly dependent on metal ion type ranging from 14 to 199 equiv NH4 +/complex after protonolysis for the Mn to Co congeners, respectively. For the series of complexes, the number of turnovers trend observed is Co > Fe > Cr > Ni > Mn, consistent with prior reports of greater efficacy of Co over Fe in other ligand systems for this reaction.

Synthetic Factors Governing Access to Tris(ß-diketimine) Cyclophanes versus Tripodal Tri-ß-aminoenones.

Tris(ß-diketimine) cyclophanes are an important ligand class for investigating cooperative multimetallic interactions of bioinorganic clusters. Discussed herein are the synthetic factors governing access to tris(ß-diketimine) cyclophanes versus tripodal tri-ß-aminoenones. Cyclophanes bearing Me, Et, and MeO cap substituents and ß-Me, Et, or Ph arm substituents are obtained, and a modified condensation method produced α-Me ß-Me cyclophane. These operationally simple procedures produce the ligands in gram quantities and in 22-94% yields.

Activation of Dinitrogen by Polynuclear Metal Complexes.

Activation of dinitrogen plays an important role in daily anthropogenic life, and the processes by which this fixation occurs have been a longstanding and significant research focus within the community. One of the major fields of dinitrogen activation research is the use of multimetallic compounds to reduce and/or activate N2 into a more useful nitrogen-atom source, such as ammonia. Here we report a comprehensive review of multimetallic-dinitrogen complexes and their utility toward N2 activation, beginning with the d-block metals from Group 4 to Group 11, then extending to Group 13 (which is exclusively populated by B complexes), and finally the rare-earth and actinide species. The review considers all polynuclear metal aggregates containing two or more metal centers in which dinitrogen is coordinated or activated (i.e., partial or complete cleavage of the N2 triple bond in the observed product). Our survey includes complexes in which mononuclear N2 complexes are used as building blocks to generate homo- or heteromultimetallic dinitrogen species, which allow one to evaluate the potential of heterometallic species for dinitrogen activation. We highlight some of the common trends throughout the periodic table, such as the differences between coordination modes as it relates to N2 activation and potential functionalization and the effect of polarizing the bridging N2 ligand by employing different metal ions of differing Lewis acidities. By providing this comprehensive treatment of polynuclear metal dinitrogen species, this Review aims to outline the past and provide potential future directions for continued research in this area.

Carbon Dioxide Insertion into Bridging Iron Hydrides: Kinetic and Mechanistic Studies.

The reduction of CO2 to formic acid by transition metal hydrides is a potential pathway to access reactive C1 compounds. To date, no kinetic study has been reported for insertion of a bridging hydride in a weak-field ligated complex into CO2; such centers have relevance to metalloenzymes that catalyze this reaction. Herein, we report the kinetic study of the reaction of a tri(µ-hydride)triiron(II/II/II) cluster supported by a tris(ß-diketimine) cyclophane (1) with CO2 monitored by 1H-NMR and temperature-controlled UV-vis spectroscopy. We found that 1 reacts with CO2 to traverse the reported monoformate (1-CO 2 ) and a diformate complex (1-2CO 2 ) at 298 K in toluene, and ultimately yields the triformate species (1-3CO 2 ) at elevated temperature. The second order rate constant, H/D kinetic isotope effect, ∆H ‡,and ∆S ‡for formation of 1-CO 2 were determined as 8.4(3)×10-4 M-1·s-1, 1.08(9), 11(1) kcal·mol-1, and -3(1)×10 cal·mol-1·K-1, respectively at 298 K. These parameters suggest that CO2 coordination to the iron centers does not coordinate prior to the rate controlling step whereas Fe-H bond cleavage does.

Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.

PURPOSE: Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE: PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS: Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS: Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.

Isolation of chloride- and hydride-bridged tri-iron and -zinc clusters in a tris(ß-oxo-δ-diimine) cyclophane ligand.

A cyclophane ligand (H6L) bearing three ß-oxo-δ-diimine arms and the corresponding tri-iron and -zinc complexes in which the metal ions are bridged by either chlorides, viz. Fe3Cl3(H3L) (1) and Zn3Cl3(H3L) (2), or hydrides, viz. Fe3H3(H3L) (3), Zn3H3(H3L) (4), were synthesized and characterized. 1 adopts a chair-shaped C3v-symmetric [Fe3(µ-Cl)3]3+ cluster wherein only one hemisphere of the ligand is metallated and the other three ketoimine sites remain protonated as evidenced by single crystal X-ray diffraction and vibrational and NMR spectroscopic analyses. 3 and 4 were synthesized by substitution of the bridging chlorides in 1 and 2 using KBEt3H and are accessed with retention of the three protonated ketoimine sites.

Cyclophanes as Platforms for Reactive Multimetallic Complexes.

Multimetallic cofactors supported by weak-field donors frequently function as reaction centers in metalloproteins, and many of these cofactors catalyze small molecule activation (e.g., N2, O2, CO2) with prominent roles in geochemical element cycles or detoxification. Notable examples include the iron-molybdenum cofactor of the molybdenum-dependent nitrogenases, which catalyze N2 fixation, and the NiFe4S4 cluster and the Mo(O)SCu site in various carbon monoxide dehydrogenases. The prevailing proposed reaction mechanisms for these multimetallic cofactors relies on a cooperative pathway, in which the oxidation state changes are distributed over the aggregate coupled with orbital overlap between the substrate and more than one metal ion within the cluster. Such cooperativity has also been proposed for chemical transformations at the surfaces of heterogeneous catalysts. However, the design details that afford cooperative effects and allow such reactivity to be harnessed effectively in homogeneous synthetic systems remain unclear. Relatedly, hydride donors ligated to these metal cluster cofactors are suggested as precursors to the state that reacts with substrates; here too, however, the reactivity of hydride-decorated clusters supported by weak-field ligands is underexplored. Inspired by the reactivity potential of multimetallic assemblies evidenced in biological systems, approaches to design, synthesize, and evaluate reactivity of polynuclear metal compounds have been actively explored. In a similar vein to the templating function afforded by enzyme active sites, a carefully engineered organic ligand can be employed to control metal nuclearity of the complex and the local coordination environment of each metal center. This Account presents our efforts within this field, beginning with ligand design considerations followed by a survey of observed small molecule activation by trimetallic cyclophanates. We highlight the distinct reactivity outcomes accessed by multimetallic compounds as compared to aggregates that assemble in reaction mixtures from monometallic precursors. Contributing to the opportunity for programmed cooperativity in these designed multimetallic compounds, the cyclophane also dictates the orientation of substrate binding and metal-substrate interactions, which has a prominent influence on reactivity. For example, the dinitrogen-tricopper(I) cyclophanate reacts with dioxygen with markedly different results as compared to monocopper compounds. As an unexpected outcome, one series of tricopper compounds were discovered to be competent catalysts for carbon dioxide reduction to oxalate-a formally one-electron process-hinting at an inherently broader reaction scope for weak-field clusters at lowering the barrier for one-electron pathways as well as multielectron redox transformations. Further reflecting the role of the ligand in tuning reactivity, the trimetallic trihydride cluster compounds, [M3(µ-H)3]3+ (M = FeII, CoII, ZnII), demonstrate substrate specificity for CO2 over various other unsaturated molecules and surprising stability toward water. This series reflects the role of the local environment of a shallow ligand pocket to control substrate access. Summed together, the systems described here evidence the anticipated cooperative reactivity accessed in designed multimetallic species vs self-assembled monometallic systems (e.g., O2 activation and O atom transfer) as well as control of substrate access by seemingly subtle structural effects. Indeed, future efforts aim to interrogate the limits of cooperativity in these systems as well as the role of ligand dynamics and sterics on reactivity.

Catalytic Silylation of Dinitrogen by a Family of Triiron Complexes.

A series of triiron complexes supported by a tris(ß-diketiminate)cyclophane (L 3- ) catalyze the reduction of dinitrogen to tris(trimethylsilyl)amine using KC8 and Me3SiCl. Employing Fe3Br3 L affords 83 ± 7 equiv. NH4 +/complex after protonolysis, which is a 50% yield based on reducing equivalents. The series of triiron compounds tested evidences the subtle effects of ancillary donors, including halides, hydrides, sulfides, and carbonyl ligands, and metal oxidation state on N(SiMe3)3 yield, and highlight Fe3(µ3-N)L as a common species in product mixtures. These results suggest that ancillary ligands can be abstracted with Lewis acids under reducing conditions.

Chalcogen Impact on Covalency within Molecular [Cu3(µ3-E)]3+ Clusters (E = O, S, Se): A Synthetic, Spectroscopic, and Computational Study.

Reaction of the tricopper(I)-dinitrogen tris(ß-diketiminate) cyclophane, Cu3(N2)L, with O-atom-transfer reagents or elemental Se affords the oxido-bridged tricopper complex Cu3(µ3-O)L (2) or the corresponding Cu3(µ3-Se)L (4), respectively. For 2 and 4, incorporation of the bridging chalcogen donor was supported by electrospray ionization mass spectrometry and K-edge X-ray absorption spectroscopy (XAS) data. Cu L2,3-edge X-ray absorption data quantify 49.5% Cu 3d character in the lowest unoccupied molecular orbital of 2, with Cu 3d participation decreasing to 33.0% in 4 and 40.8% in the related sulfide cluster Cu3(µ3-S)L (3). Multiedge XAS and UV/visible/near-IR spectra are employed to benchmark density functional theory calculations, which describe the copper-chalcogen interactions as highly covalent across the series of [Cu3(µ-E)]3+ clusters. This result highlights that the metal-ligand covalency is not reserved for more formally oxidized metal centers (i.e., CuIII + O2- vs CuII + O-) but rather is a significant contributor even at more typical ligand-field cases (i.e., Cu3II/II/I + E2-). This bonding is reminiscent of that observed in p-block elements rather than in early-transition-metal complexes.

A Tricopper(I) Complex Competent for O Atom Transfer, C-H Bond Activation, and Multiple O2 Activation Steps.

Oxygenation of a tricopper(I) cyclophanate (1) affords reactive transients competent for C-H bond activation and O atom transfer to various substrates (including toluene, dihydroanthracene, and ethylmethylsulfide) based on 1H NMR, gas chromatography/mass spectrometry (MS), and electrospray ionization (ESI)/MS data. Low product yields (<1%) are determined for C-H activation substrates (e.g, toluene, ethylbenzene), which we attribute to competitive ligand oxidation. The combined stopped-flow UV/visible, electron paramagnetic resonance, ESI/MS, 1H NMR, and density functional theory (DFT) results for reaction of 1 with O2 are consistent with transient peroxo- and di(oxo)-bridged intermediates. DFT calculations elucidate a concerted proton-coupled electron transfer from toluene to the di(µ-oxo) intermediate and subsequent radical rebound as the C-H activation mechanism. Our results support a multicopper oxidase-like mechanism for O2 activation by 1, traversing species similar to the coplanar Cu3O2 unit in the peroxy and native intermediates.

Countercations and Solvent Influence CO2 Reduction to Oxalate by Chalcogen-Bridged Tricopper Cyclophanates.

One-electron reduction of Cu3EL (L3- = tris(ß-diketiminate)cyclophane, and E = S, Se) affords [Cu3EL]-, which reacts with CO2 to yield exclusively C2O42- (95% yield, TON = 24) and regenerate Cu3EL. Stopped-flow UV/visible data support an A→B mechanism under pseudo-first-order conditions ( kobs, 298K = 115(2) s-1), which is 106 larger than those for reported copper complexes. The kobs values are dependent on the countercation and solvent (e.g., kobs is greater for [K(18-crown-6)]+ vs (Ph3P)2N+, and there is a 20-fold decrease in kobs in THF vs DMF). Our results suggest a mechanism in which cations and solvent influence the stability of the transition state.

Correlating Bridging Ligand with Properties of Ligand-Templated [MnII3X3]3+ Clusters (X = Br-, Cl-, H-, MeO-).

Polynuclear manganese compounds have garnered interest as mimics and models of the water oxidizing complex (WOC) in photosystem II and as single molecule magnets. Molecular systems in which composition can be correlated to physical phenomena, such as magnetic exchange interactions, remain few primarily because of synthetic limitations. Here, we report the synthesis of a family of trimanganese(II) complexes of the type Mn3X3L (X = Cl-, H-, and MeO-) where L3- is a tris(ß-diketiminate) cyclophane. The tri(chloride) complex (2) is structurally similar to the reported tri(bromide) complex (1) with the Mn3X3 core having a ladder-like arrangement of alternating M-X rungs, whereas the tri(µ-hydride) (3) and tri(µ-methoxide) (4) complexes contain planar hexagonal cores. The hydride and methoxide complexes are synthesized in good yield (48% and 56%) starting with the bromide complex employing a metathesis-like strategy. Compounds 2-4 were characterized by combustion analysis, X-ray crystallography, X-band EPR spectroscopy, SQUID magnetometry, and infrared and UV-visible spectroscopy. Magnetic susceptibility measurements indicate that the Mn3 clusters in 2-4 are antiferromagnetically coupled, and the spin ground state of the compounds (S = 3/2 (1, 2) or S = 1/2 (3, 4)) is correlated to the identity of the bridging ligand and structural arrangement of the Mn3X3 core (X = Br, Cl, H, OCH3). Electrochemical experiments on isobutyronitrile solutions of 3 and 4 display broad irreversible oxidations centered at 0.30 V.

Reactivity of hydride bridges in a high-spin [Fe3(µ-H)3]3+ cluster: reversible H2/CO exchange and Fe-H/B-F bond metathesis.

The triiron trihydride complex Fe3H3L (1) [where L3- is a tris(ß-diketiminate)cyclophanate] reacts with CO and with BF3·OEt2 to afford (FeICO)2FeII(µ3-H)L (2) and Fe3F3L (3), respectively. Variable-temperature and applied-field Mössbauer spectroscopy support the assignment of two high-spin (HS) iron(i) centers and one HS iron(ii) ion in 2. Preliminary studies support a CO-induced reductive elimination of H2 from 1, rather than CO trapping a species from an equilibrium mixture. This complex reacts with H2 to regenerate 1 under a dihydrogen atmosphere, which represents a rare example of reversible CO/H2 exchange and the first to occur at high-spin metal centers, as well as the first example of a reversible multielectron redox reaction at a designed high-spin metal cluster. The formation of 3 proceeds through a previously unreported net fluoride-for-hydride substitution, and 3 is surprisingly chemically inert to Si-H bonds and points to an unexpectedly large difference between the Fe-F and Fe-H bonds in this high-spin system.