Generation, Characterization and Reactivity of a High-Valent Mononuclear Cobalt(IV)-Diazide Complex.

High-valent Fe(IV)=O intermediates of metalloenzymes have inspired numerous efforts to generate synthetic analogs to mimic and understand their substrate oxidation reactivities. However, high-valent M(IV) complexes of late transition metals are rare. We have recently reported a novel Co(IV)-dinitrate complex (1-NO3) that activates sp3 C-H bonds up to 87 kcal/mol. In this work, we have shown that the nitrate ligands in 1-NO3 can be replaced by azide, a more basic coordinating base, resulting in the formation of a more potent Co(IV)-diazide species (1-N3) that reacts with substrates (hydrocarbons and phenols) at faster rate constants and activates stronger C-H bonds than the parent complex 1-NO3. We have characterized 1-N3 employing a combination of spectroscopic and computational approaches. Our results clearly show that the coordination of azide leads to the modulation of the Co(IV) electronic structure and the Co(IV/III) redox potential. Together with the higher basicity of azide, these thermodynamic parameters contribute to the higher driving forces of 1-N3 than 1-NO3 for C-H bond activation. Our discoveries are thus insightful for designing more reactive bio-inspired high-valent late transition metal complexes for activating inert aliphatic hydrocarbons.

C-H Bond Oxidation by MnIV-Oxo Complexes: Hydrogen-Atom Tunneling and Multistate Reactivity.

The reactivity of six MnIV-oxo complexes in C-H bond oxidation has been examined using a combination of kinetic experiments and computational methods. Variable-temperature studies of the oxidation of 9,10-dihydroanthracene (DHA) and ethylbenzene by these MnIV-oxo complexes yielded activation parameters suitable for evaluating electronic structure computations. Complementary kinetic experiments of the oxidation of deuterated DHA provided evidence for hydrogen-atom tunneling in C-H bond oxidation for all MnIV-oxo complexes. These results are in accordance with the Bell model, where tunneling occurs near the top of the transition-state barrier. Density functional theory (DFT) and DLPNO-CCSD(T1) computations were performed for three of the six MnIV-oxo complexes to probe a previously predicted multistate reactivity model. The DFT computations predicted a thermal crossing from the 4B1 ground state to a 4E state along the C-H bond oxidation reaction coordinate. DLPNO-CCSD(T1) calculations further confirm that the 4E transition state offers a lower energy barrier, reinforcing the multistate reactivity model for these complexes. We discuss how this multistate model can be reconciled with recent computations that revealed that the kinetics of C-H bond oxidation by this set of MnIV-oxo complexes can be well-predicted on the basis of the thermodynamic driving force for these reactions.

Investigating Ligand Sphere Perturbations on MnIII-Alkylperoxo Complexes.

Manganese catalysts that activate hydrogen peroxide carry out several different hydrocarbon oxidation reactions with high stereoselectivity. The commonly proposed mechanism for these reactions involves a key manganese(III)-hydroperoxo intermediate, which decays via O-O bond heterolysis to generate a Mn(V)-oxo species that institutes substrate oxidation. Due to the scarcity of characterized MnIII-hydroperoxo complexes, MnIII-alkylperoxo complexes are employed to understand factors that affect the mechanism of the O-O cleavage. Herein, we report a series of novel complexes, including two room-temperature-stable MnIII-alkylperoxo species, supported by a new amide-containing pentadentate ligand (6Medpaq5NO2). We use a combination of spectroscopic methods and density functional theory computations to probe the effects of the electronic changes in the ligand sphere trans to the hydroxo and alkylperoxo units to thermal stability and reactivity. The structural characterizations for both MnII(OTf)(6Medpaq5NO2) and [MnIII(OH)(6Medpaq5NO2)](OTf) were obtained via single-crystal X-ray crystallography. A perturbation to the ligand sphere allowed for a marked increase in reactivity towards an organic substrate, a modest change in the distribution of the O-O cleavage products from homolytic and heterolytic pathways, and little change in thermal stability.

Enhanced Understanding of Structure-Function Relationships for Oxomanganese(IV) Complexes.

A series of manganese(II) and oxomanganese(IV) complexes supported by neutral, pentadentate ligands with varied equatorial ligand-field strength (N3pyQ, N2py2I, and N4pyMe2) were synthesized and then characterized using structural and spectroscopic methods. On the basis of electronic absorption spectroscopy, the [MnIV(O)(N4pyMe2)]2+ complex has the weakest equatorial ligand field among a set of similar MnIV-oxo species. In contrast, [MnIV(O)(N2py2I)]2+ shows the strongest equatorial ligand-field strength for this same series. We examined the influence of these changes in electronic structure on the reactivity of the oxomanganese(IV) complexes using hydrocarbons and thioanisole as substrates. The [MnIV(O)(N3pyQ)]2+ complex, which contains one quinoline and three pyridine donors in the equatorial plane, ranks among the fastest MnIV-oxo complexes in C-H bond and thioanisole oxidation. While a weak equatorial ligand field has been associated with high reactivity, the [MnIV(O)(N4pyMe2)]2+ complex is only a modest oxidant. Buried volume plots suggest that steric factors dampen the reactivity of this complex. Trends in reactivity were examined using density functional theory (DFT)-computed bond dissociation free energies (BDFEs) of the MnIIIO-H and MnIV ═ O bonds. We observe an excellent correlation between MnIV═O BDFEs and rates of thioanisole oxidation, but more scatter is observed between hydrocarbon oxidation rates and the MnIIIO-H BDFEs.

C-H Bond Activation by a Mononuclear Nickel(IV)-Nitrate Complex.

The recent focus on developing high-valent non-oxo-metal complexes for late transition metals has proven to be an effective strategy to study the rich chemistry of these high-valent species while bypassing the synthetic challenges of obtaining the oxo-metal counterparts. In our continuing work of exploring late transition metal complexes of unusually high oxidation states, we have obtained in the present study a formal mononuclear Ni(IV)-nitrate complex (2) upon 1-e- oxidation of its Ni(III) derivatives (1-OH and 1-NO3). Characterization of these Ni complexes by combined spectroscopic and computational approaches enables deep understanding of their geometric and electronic structures, bonding interactions, and spectroscopic properties, showing that all of them are square planar complexes and exhibit strong π-covalency with the amido N-donors of the N3 ligand. Furthermore, results obtained from X-ray absorption spectroscopy and density functional theory calculations provide strong support for the assignment of the Ni(IV) oxidation state of complex 2, albeit with strong ligand-to-metal charge donation. Notably, 2 is able to oxidize hydrocarbons with C-H bond strength in the range of 76-92 kcal/mol, representing a rare example of high-valent late transition metal complexes capable of activating strong sp3 C-H bonds.

Evidence for the Chemical Mechanism of RibB (3,4-Dihydroxy-2-butanone 4-phosphate Synthase) of Riboflavin Biosynthesis.

RibB (3,4-dihydroxy-2-butanone 4-phosphate synthase) is a magnesium-dependent enzyme that excises the C4 of d-ribulose-5-phosphate (d-Ru5P) as formate. RibB generates the four-carbon substrate for lumazine synthase that is incorporated into the xylene moiety of lumazine and ultimately the riboflavin isoalloxazine. The reaction was first identified by Bacher and co-workers in the 1990s, and their chemical mechanism hypothesis became canonical despite minimal direct evidence. X-ray crystal structures of RibB typically show two metal ions when solved in the presence of non-native metals and/or liganding non-substrate analogues, and the consensus hypothetical mechanism has incorporated this cofactor set. We have used a variety of biochemical approaches to further characterize the chemistry catalyzed by RibB from Vibrio cholera (VcRibB). We show that full activity is achieved at metal ion concentrations equal to the enzyme concentration. This was confirmed by electron paramagnetic resonance of the enzyme reconstituted with manganese and crystal structures liganded with Mn2+ and a variety of sugar phosphates. Two transient species prior to the formation of products were identified using acid quench of single turnover reactions in combination with NMR for singly and fully 13C-labeled d-Ru5P. These data indicate that dehydration of C1 forms the first transient species, which undergoes rearrangement by a 1,2 migration, fusing C5 to C3 and generating a hydrated C4 that is poised for elimination as formate. Structures determined from time-dependent Mn2+ soaks of VcRibB-d-Ru5P crystals show accumulation in crystallo of the same intermediates. Collectively, these data reveal for the first time crucial transient chemical states in the mechanism of RibB.

Near-UV and Visible Light Degradation of Iron (III)-Containing Citrate Buffer: Formation of Carbon Dioxide Radical Anion via Fragmentation of a Sterically Hindered Alkoxyl Radical.

Citrate is a commonly used buffer in pharmaceutical formulations which forms complexes with adventitious metals such as Fe3+. Fe3+-citrate complexes can act as potent photosensitizers under near-UV and visible light exposure, and recent studies reported evidence for the photo-production of a powerful reductant, carbon dioxide radical anion (•CO2-), from Fe3+-citrate complexes (Subelzu, N.; Schöneich, N., Mol. Pharm. 2020, 17, 4163-4179). The mechanisms of •CO2- formation are currently unknown but must be established to devise strategies against •CO2- formation in pharmaceutical formulations which rely on the use of citrate buffer. In this study, we first established complementary evidence for the photolytic generation of •CO2- from Fe3+-citrate through spin trapping and electron paramagnetic resonance (EPR) spectroscopy, and subsequently used spin trapping in conjunction with tandem mass spectrometry (MS/MS) for mechanistic studies on the pathways of •CO2- formation. Experiments with stable isotope-labeled citrate suggest that the central carboxylate group of citrate is the major source of •CO2-. Competition studies with various inhibitors (alcohols and dimethyl sulfoxide) reveal two mechanisms of •CO2- formation, where one pathway involves ß-cleavage of a sterically hindered alkoxyl radical generated from the hydroxyl group of citrate.

Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2.

Lysyl oxidase-2 (LOXL2) is a Cu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidase that catalyzes the oxidative deamination of peptidyl lysine and hydroxylysine residues to promote crosslinking of extracellular matrix proteins. LTQ is post-translationally derived from Lys653 and Tyr689, but its biogenesis mechanism remains still elusive. A 2.4 Å Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 Å apart, thus a substantial conformational rearrangement is expected to take place for LTQ biogenesis. However, we have recently shown that the overall structures of the precursor (no LTQ) and the mature (LTQ-containing) LOXL2s are very similar and disulfide bonds are conserved. In this study, we aim to gain insights into the spatial arrangement of LTQ and the active site Cu2+ in the mature LOXL2 using a recombinant LOXL2 that is inhibited by 2-hydrazinopyridine (2HP). Comparative UV-vis and resonance Raman spectroscopic studies of the 2HP-inhibited LOXL2 and the corresponding model compounds and an EPR study of the latter support that 2HP-modified LTQ serves as a tridentate ligand to the active site Cu2. We propose that LTQ resides within 2.9 Å of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed.

Controlling the Reactivity of a Metal-Hydroxo Adduct with a Hydrogen Bond.

The enzymes manganese lipoxygenase (MnLOX) and manganese superoxide dismutase (MnSOD) utilize mononuclear Mn centers to effect their catalytic reactions. In the oxidized MnIII state, the active site of each enzyme contains a hydroxo ligand, and X-ray crystal structures imply a hydrogen bond between this hydroxo ligand and a cis carboxylate ligand. While hydrogen bonding is a common feature of enzyme active sites, the importance of this particular hydroxo-carboxylate interaction is relatively unexplored. In this present study, we examined a pair of MnIII-hydroxo complexes that differ by a single functional group. One of these complexes, [MnIII(OH)(PaPy2N)]+, contains a naphthyridinyl moiety capable of forming an intramolecular hydrogen bond with the hydroxo ligand. The second complex, [MnIII(OH)(PaPy2Q)]+, contains a quinolinyl moiety that does not permit any intramolecular hydrogen bonding. Spectroscopic characterization of these complexes supports a common structure, but with perturbations to [MnIII(OH)(PaPy2N)]+, consistent with a hydrogen bond. Kinetic studies using a variety of substrates with activated O-H bonds, revealed that [MnIII(OH)(PaPy2N)]+ is far more reactive than [MnIII(OH)(PaPy2Q)]+, with rate enhancements of 15-100-fold. A detailed analysis of the thermodynamic contributions to these reactions using DFT computations reveals that the former complex is significantly more basic. This increased basicity counteracts the more negative reduction potential of this complex, leading to a stronger O-H BDFE in the [MnII(OH2)(PaPy2N)]+ product. Thus, the differences in reactivity between [MnIII(OH)(PaPy2Q)]+ and [MnIII(OH)(PaPy2N)]+ can be understood on the basis of thermodynamic considerations, which are strongly influenced by the ability of the latter complex to form an intramolecular hydrogen bond.

Electronic Structure and Magnetic Properties of a Low-Spin CrII Complex: trans-[CrCl2(dmpe)2] (dmpe = 1,2-Bis(dimethylphosphino)ethane).

Octahedral coordination complexes of the general formula trans-[MX2(R2ECH2CH2ER2)2] (MII = Ti, V, Cr, Mn; E = N, P; R = alkyl, aryl) are a cornerstone of both coordination and organometallic chemistry, and many of these complexes are known to have unique electronic structures that have been incompletely examined. The trans-[CrCl2(dmpe)2] complex (dmpe = Me2PCH2CH2PMe2), originally reported by Girolami and co-workers in 1985, is a rare example of a six-coordinate d4 system with an S = 1 (spin triplet) ground state, as opposed to the high-spin (S = 2, spin quintet) state. The ground-state properties of S = 1 systems are challenging to study using conventional spectroscopic methods, and consequently, the electronic structure of trans-[CrCl2(dmpe)2] has remained largely unexplored. In this present work, we have employed high-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy to characterize the ground-state electronic structure of trans-[CrCl2(dmpe)2]. This analysis yielded a complete set of spin Hamiltonian parameters for this S = 1 complex: D = +7.39(1) cm-1, E = +0.093(1) (E/D = 0.012), and g = [1.999(5), 2.00(1), 2.00(1)]. To develop a detailed electronic structure description for trans-[CrCl2(dmpe)2], we employed both classical ligand-field theory and quantum chemical theory (QCT) calculations, which considered all quintet, triplet, and singlet ligand-field states. While the high density of states suggests an unexpectedly complex electronic structure for this "simple" coordination complex, both the ligand-field and QCT methods were able to reproduce the experimental spin Hamiltonian parameters quite nicely. The QCT computations were also used as a basis for assigning the electronic absorption spectrum of trans-[CrCl2(dmpe)2] in toluene.

Probing the Mechanism for 2,4'-Dihydroxyacetophenone Dioxygenase Using Biomimetic Iron Complexes.

In this study, we report the synthesis and characterization of [Fe(T1Et4iPrIP)(2-OH-AP)(OTf)](OTf) (2), [Fe(T1Et4iPrIP)(2-O-AP)](OTf) (3), and [Fe(T1Et4iPrIP)(DMF)3](OTf)3 (4) (T1Et4iPrIP = tris(1-ethyl-4-isopropyl-imidazolyl)phosphine; 2-OH-AP = 2-hydroxyacetophenone, and 2-O-AP- = monodeprotonated 2-hydroxyacetophenone). Both 2 and 3 serve as model complexes for the enzyme-substrate adduct for the nonheme enzyme 2,4'-dihydroacetophenone (DHAP) dioxygenase or DAD, while 4 serves as a model for the ferric form of DAD. Complexes 2-4 have been characterized by X-ray crystallography which reveals T1Et4iPrIP to bind iron in a tridentate fashion. Complex 2 additionally contains a bidentate 2-OH-AP ligand and a monodentate triflate ligand yielding distorted octahedral geometry, while 3 possesses a bidentate 2-O-AP- ligand and exhibits distorted trigonal bipyramidal geometry (τ = 0.56). Complex 4 displays distorted octahedral geometry with 3 DMF ligands completing the ligand set. The UV-vis spectrum of 2 matches more closely to the DAD-substrate spectrum than 3, and therefore, it is believed that the substrate for DAD is bound in the protonated form. TD-DFT studies indicate that visible absorption bands for 2 and 3 are due to MLCT bands. Complexes 2 and 3 are capable of oxidizing the coordinated substrate mimics in a stoichiometric and catalytic fashion in the presence of O2. Complex 4 does not convert 2-OH-AP to products under the same catalytic conditions; however, it becomes anaerobically reduced in the presence of 2 equiv 2-OH-AP to 2.

Mimicking Elementary Reactions of Manganese Lipoxygenase Using Mn-hydroxo and Mn-alkylperoxo Complexes.

Manganese lipoxygenase (MnLOX) is an enzyme that converts polyunsaturated fatty acids to alkyl hydroperoxides. In proposed mechanisms for this enzyme, the transfer of a hydrogen atom from a substrate C-H bond to an active-site MnIII-hydroxo center initiates substrate oxidation. In some proposed mechanisms, the active-site MnIII-hydroxo complex is regenerated by the reaction of a MnIII-alkylperoxo intermediate with water by a ligand substitution reaction. In a recent study, we described a pair of MnIII-hydroxo and MnIII-alkylperoxo complexes supported by the same amide-containing pentadentate ligand (6Medpaq). In this present work, we describe the reaction of the MnIII-hydroxo unit in C-H and O-H bond oxidation processes, thus mimicking one of the elementary reactions of the MnLOX enzyme. An analysis of kinetic data shows that the MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ oxidizes TEMPOH (2,2'-6,6'-tetramethylpiperidine-1-ol) faster than the majority of previously reported MnIII-hydroxo complexes. Using a combination of cyclic voltammetry and electronic structure computations, we demonstrate that the weak MnIII-N(pyridine) bonds lead to a higher MnIII/II reduction potential, increasing the driving force for substrate oxidation reactions and accounting for the faster reaction rate. In addition, we demonstrate that the MnIII-alkylperoxo complex [MnIII(OOtBu)(6Medpaq)]+ reacts with water to obtain the corresponding MnIII-hydroxo species, thus mimicking the ligand substitution step proposed for MnLOX.

Crystal Structure and C-H Bond-Cleaving Reactivity of a Mononuclear CoIV-Dinitrate Complex.

High-valent FeIV═O intermediates with a terminal metal-oxo moiety are key oxidants in many enzymatic and synthetic C-H bond oxidation reactions. While generating stable metal-oxo species for late transition metals remains synthetically challenging, notably, a number of high-valent non-oxo-metal species of late transition metals have been recently described as strong oxidants that activate C-H bonds. In this work, we obtained an unprecedented mononuclear CoIV-dinitrate complex (2) upon one-electron oxidation of its Co(III) precursor supported by a tridentate dianionic N3 ligand. 2 was structurally characterized by X-ray crystallography, showing a square pyramidal geometry with two coordinated nitrate anions. Furthermore, characterization of 2 using combined spectroscopic and computational methods revealed that 2 is a low-spin (S = 1/2) Co(IV) species with the unpaired electron located on the cobalt dz2 orbital, which is well positioned for substrate oxidations. Indeed, while having a high thermal stability, 2 is able to cleave sp3 C-H bonds up to 87 kcal/mol to afford rate constants and kinetic isotope effects (KIEs) of 2-6 that are comparable to other high-valent metal oxidants. The ability to oxidize strong C-H bonds has yet to be observed for CoIV-O and CoIII═O species previously reported. Therefore, 2 represents the first high-valent Co(IV) species that is both structurally characterized by X-ray crystallography and capable of activating strong C-H bonds.

Structural Characterization of a Series of N5-Ligated MnIV -Oxo Species.

Analysis of extended X-ray absorption fine structure (EXAFS) data for the MnIV -oxo complexes [MnIV (O)(DMM N4py)]2+ , [MnIV (O)(2pyN2B)]2+ , and [MnIV (O)(2pyN2Q)]2+ (DMM N4py=N,N-bis(4-methoxy-3,5-dimethyl-2-pyridylmethyl)-N-bis(2-pyridyl)methylamine; 2pyN2B=(N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine, and 2pyN2Q=N,N-bis(2-pyridyl)-N,N-bis(2-quinolylmethyl)methanamine) afforded Mn=O and Mn-N bond lengths. The Mn=O distances for [MnIV (O)(DMM N4py)]2+ and [MnIV (O)(2pyN2B)]2+ are 1.72 and 1.70 Å, respectively. In contrast, the Mn=O distance for [MnIV (O)(2pyN2Q)]2+ was significantly longer (1.76 Å). We attribute this long distance to sample heterogeneity, which is reasonable given the reduced stability of [MnIV (O)(2pyN2Q)]2+ . The Mn=O distances for [MnIV (O)(DMM N4py)]2+ and [MnIV (O)(2pyN2B)]2+ could only be well-reproduced using DFT-derived models that included strong hydrogen-bonds between second-sphere solvent 2,2,2-trifluoroethanol molecules and the oxo ligand. These results suggest an important role for the 2,2,2-trifluoroethanol solvent in stabilizing MnIV -oxo adducts. The DFT methods were extended to investigate the structure of the putative [MnIV (O)(N4py)]2+ ⋅(HOTf)2 adduct. These computations suggest that a MnIV -hydroxo species is most consistent with the available experimental data.

Effect of Lewis Acids on the Structure and Reactivity of a Mononuclear Hydroxomanganese(III) Complex.

The addition of Sc(OTf)3 and Al(OTf)3 to the mononuclear MnIII-hydroxo complex [MnIII(OH)(dpaq)]+ (1) gives rise to new intermediates with spectroscopic properties and chemical reactivity distinct from those of [MnIII(OH)(dpaq)]+. The electronic absorption spectra of [MnIII(OH)(dpaq)]+ in the presence of Sc(OTf)3 (1-ScIII) and Al(OTf)3 (1-AlIII) show modest perturbations in electronic transition energies, consistent with moderate changes in the MnIII geometry. A comparison of 1H NMR data for 1 and 1-ScIII confirm this conclusion, as the 1H NMR spectrum of 1-ScIII shows the same number of hyperfine-shifted peaks as the 1H NMR spectrum of 1. These 1H NMR spectra, and that of 1-AlIII, share a similar chemical-shift pattern, providing firm evidence that these Lewis acids do not cause gross distortions to the structure of 1. Mn K-edge X-ray absorption data for 1-ScIII provide evidence of elongation of the axial Mn-OH and Mn-N(amide) bonds relative to those of 1. In contrast to these modest spectroscopic perturbations, 1-ScIII and 1-AlIII show greatly enhanced reactivity toward hydrocarbons. While 1 is unreactive toward 9,10-dihydroanthracene (DHA), 1-ScIII and 1-AlIII react rapidly with DHA (k2 = 0.16(1) and 0.25(2) M-1 s-1 at 50 °C, respectively). The 1-ScIII species is capable of attacking the much stronger C-H bond of ethylbenzene. The basis for these perturbations to the spectroscopic properties and reactivity of 1 in the presence of these Lewis acids was elucidated by comparing properties of 1-ScIII and 1-AlIII with the recently reported MnIII-aqua complex [MnIII(OH2)(dpaq)]2+ ( J. Am. Chem. Soc. 2018, 140, 12695-12699). Because 1-ScIII and 1-AlIII show 1H NMR spectra essentially identical to that of [MnIII(OH2)(dpaq)]2+, the primary effect of these Lewis acids on 1 is protonation of the hydroxo ligand caused by an increase in the Brønsted acidity of the solution.

Electronic Structure and Magnetic Properties of a Titanium(II) Coordination Complex.

Stable coordination complexes of TiII (3d2) are relatively uncommon, but are of interest as synthons for low oxidation state titanium complexes for application as potential catalysts and reagents for organic synthesis. Specifically, high-spin TiII ions supported by redox-inactive ligands are still quite rare due to the reducing power of this soft ion. Among such TiII complexes is trans-[TiCl2(tmeda)2], where tmeda = N,N,N',N'-tetramethylethane-1,2-diamine. This complex was first reported by Gambarotta and co-workers almost 30 years ago, but it was not spectroscopically characterized and theoretical investigation by quantum chemical theory (QCT) was not feasible at that time. As part of our interest in low oxidation state early transition metal complexes, we have revisited this complex and report a modified synthesis and a low temperature (100 K) crystal structure that differs slightly from that originally reported at ambient temperature. We have used magnetometry, high-frequency and -field EPR (HFEPR), and variable-temperature variable-field magnetic circular dichroism (VTVH-MCD) spectroscopies to characterize trans-[TiCl2(tmeda)2]. These techniques yield the following S = 1 spin Hamiltonian parameters for the complex: D = -5.23(1) cm-1, E = -0.88(1) cm-1, (E/D = 0.17), g = [1.86(1), 1.94(2), 1.77(1)]. This information, in combination with electronic transitions from MCD, was used as input for both classical ligand-field theory (LFT) and detailed QCT studies, the latter including both density functional theory (DFT) and ab initio methods. These computational methods are seldom applied to paramagnetic early transition metal complexes, particularly those with S > 1/2. Our studies provide a complete picture of the electronic structure of this complex that can be put into context with the few other high-spin and mononuclear TiII species characterized to date.

Experimental and Multireference ab Initio Investigations of Hydrogen-Atom-Transfer Reactivity of a Mononuclear MnIV-oxo Complex.

A combined experimental-computational study of hydrocarbon oxidation by the MnIV-oxo complex of the neutral, pentadentate N4py ligand [N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine] offers support for a complex reaction coordinate involving multiple electronic states. Variable-temperature kinetic investigations of ethylbenzene oxidation by [MnIV(O)(N4py)]2+ yield experimental activation parameters that were used to evaluate computationally predicted energy barriers. Both density functional theory (DFT) and multireference complete-active-space self-consistent-field (CASSCF) computations with n-electron valence state perturbation theory (NEVPT2) corrections were employed to investigate the hydrogen-atom-transfer reaction barriers for the 4B1 and 4E states. The 4B1 state is the ground state in the absence of substrate, and the 4E state is related to the ground state by a one-electron MnIV e(dxz,3dyz) to MnIV b1(dx2-y2) excitation. A comparison of the DFT, CASSCF/NEVPT2, and experimental results shows that the B3LYP-D3 method underestimates the activation barriers of both electronic states by ca. 10 kcal mol-1. In contrast, the enthalpic barrier predicted for the 4E state by the CASSCF/NEVPT2 method is within 2 kcal mol-1 of the experimental value. The 4E state is early, with dominant structural distortions in the Mn-Nequatorial distances and perturbations to Mn═O bonding that lead to strong electronic stabilization of interactions between the MnIV-oxo unit and substrate C-H bond. While previous DFT studies were qualitatively correct in their ordering of the 4B1 and 4E transition states, this combined use of experimental and CASSCF/NEVPT2 methods provides an ideal means of assessing the two-state reactivity model of MnIV-oxo complexes.

Structure and Reactivity of (µ-Oxo)dimanganese(III,III) and Mononuclear Hydroxomanganese(III) Adducts Supported by Derivatives of an Amide-Containing Pentadentate Ligand.

Mononuclear MnIII-hydroxo and dinuclear (µ-oxo)dimanganese(III,III) complexes were prepared using derivatives of the pentadentate, amide-containing dpaq ligand (dpaq = 2-[bis(pyridin-2-ylmethyl)]amino- N-quinolin-8-yl-acetamidate). Each of these ligand derivatives (referred to as dpaq5R) contained a substituent R (where R = OMe, Cl, and NO2) at the 5-position of the quinolinyl group. Generation of the MnIII complexes was achieved by either O2 oxidation of MnII precursors (for [MnII(dpaq5OMe)]+ and [MnII(dpaq5Cl)]+ or PhIO oxidation (for [MnII(dpaq5NO2)]+). For each oxidized complex, 1H NMR experiments provided evidence of a water-dependent equilibrium between paramagnetic [MnIII(OH)(dpaq5R)]+ and an antiferromagnetically coupled [MnIIIMnIII(µ-O)(dpaq5R)2]2+ species in acetonitrile, with the addition of water favoring the MnIII-hydroxo species. This conversion could also be monitored by electronic absorption spectroscopy. Solid-state X-ray crystal structures for each [MnIIIMnIII(µ-O)(dpaq5R)2](OTf)2 complex revealed a nearly linear Mn-O-Mn core (angle of ca. 177°), with short Mn-O distances near 1.79 Å, and a Mn···Mn separation of 3.58 Å. X-ray crystallographic information was also obtained for the mononuclear [MnIII(OH)(dpaq5Cl)](OTf) complex, which has a short Mn-O(H) distance of 1.810(2) Å. The influence of the 5-substituted quinolinyl moiety on the electronic properties of the [MnIII(OH)(dpaq5R)]+ complexes was demonstrated through shifts in a number of 1H NMR resonances, as well as a steady increase in the MnIII/II cyclic voltammetry peak potential in the order [MnIII(OH)(dpaq5OMe)]+ < [MnIII(OH)(dpaq)]+ < [MnIII(OH)(dpaq5Cl)]+ < [MnIII(OH)(dpaq5NO2)]+. These changes in oxidizing power of the MnIII-hydroxo adducts translated to only modest rate enhancements for TEMPOH oxidation by the [MnIII(OH)(dpaq5R)]+ complexes, with the most reactive [MnIII(OH)(dpaq5NO2)]+ complex showing a second-order rate constant only 9-fold larger than that of the least reactive [MnIII(OH)(dpaq5OMe)]+ complex. These modest rate changes were understood on the basis of density functional theory (DFT)-computed p Ka values for the corresponding [MnII(OH2)(dpaq5R)]+ complexes. Collectively, the experimental and DFT results reveal that the 5-substituted quinolinyl groups have an inverse influence on electron and proton affinity for the MnIII-hydroxo unit.

Manganese-Oxygen Intermediates in O-O Bond Activation and Hydrogen-Atom Transfer Reactions.

Biological systems capitalize on the redox versatility of manganese to perform reactions involving dioxygen and its derivatives superoxide, hydrogen peroxide, and water. The reactions of manganese enzymes influence both human health and the global energy cycle. Important examples include the detoxification of reactive oxygen species by manganese superoxide dismutase, biosynthesis by manganese ribonucleotide reductase and manganese lipoxygenase, and water splitting by the oxygen-evolving complex of photosystem II. Although these enzymes perform very different reactions and employ structurally distinct active sites, manganese intermediates with peroxo, hydroxo, and oxo ligation are commonly proposed in catalytic mechanisms. These intermediates are also postulated in mechanisms of synthetic manganese oxidation catalysts, which are of interest due to the earth abundance of manganese. In this Account, we describe our recent efforts toward understanding O-O bond activation pathways of MnIII-peroxo adducts and hydrogen-atom transfer reactivity of MnIV-oxo and MnIII-hydroxo complexes. In biological and synthetic catalysts, peroxomanganese intermediates are commonly proposed to decay by either Mn-O or O-O cleavage pathways, although it is often unclear how the local coordination environment influences the decay mechanism. To address this matter, we generated a variety of MnIII-peroxo adducts with varied ligand environments. Using parallel-mode EPR and Mn K-edge X-ray absorption techniques, the decay pathway of one MnIII-peroxo complex bearing a bulky macrocylic ligand was investigated. Unlike many MnIII-peroxo model complexes that decay to oxo-bridged-MnIIIMnIV dimers, decay of this MnIII-peroxo adduct yielded mononuclear MnIII-hydroxo and MnIV-oxo products, potentially resulting from O-O bond activation of the MnIII-peroxo unit. These results highlight the role of ligand sterics in promoting the formation of mononuclear products and mark an important step in designing MnIII-peroxo complexes that convert cleanly to high-valent Mn-oxo species. Although some synthetic MnIV-oxo complexes show great potential for oxidizing substrates with strong C-H bonds, most MnIV-oxo species are sluggish oxidants. Both two-state reactivity and thermodynamic arguments have been put forth to explain these observations. To address these issues, we generated a series of MnIV-oxo complexes supported by neutral, pentadentate ligands with systematically perturbed equatorial donation. Kinetic investigations of these complexes revealed a correlation between equatorial ligand-field strength and hydrogen-atom and oxygen-atom transfer reactivity. While this trend can be understood on the basis of the two-state reactivity model, the reactivity trend also correlates with variations in MnIII/IV reduction potential caused by changes in the ligand field. This work demonstrates the dramatic influence simple ligand perturbations can have on reactivity but also illustrates the difficulties in understanding the precise basis for a change in reactivity. In the enzyme manganese lipoxygenase, an active-site MnIII-hydroxo adduct initiates substrate oxidation by abstracting a hydrogen atom from a C-H bond. Precedent for this chemistry from synthetic MnIII-hydroxo centers is rare. To better understand hydrogen-atom transfer by MnIII centers, we developed a pair of MnIII-hydroxo complexes, formed in high yield from dioxygen oxidation of MnII precursors, capable of attacking weak O-H and C-H bonds. Kinetic and computational studies show a delicate interplay between thermodynamic and steric influences in hydrogen-atom transfer reactivity, underscoring the potential of MnIII-hydroxo units as mild oxidants.

Spectroscopic and Structural Characterization of Mn(III)-Alkylperoxo Complexes Supported by Pentadentate Amide-Containing Ligands.

Manganese-alkylperoxo species have been proposed as important intermediates in certain enzymatic pathways and are presumed to play a key role in catalytic substrate oxidation cycles involving manganese catalysts and peroxide oxidants. However, structural and spectroscopic understanding of these intermediates is very limited, with only one series of synthetic MnIII-alkylperoxo complexes having been reported. In the present study, we describe the formation and properties of two new MnIII-alkylperoxo complexes, namely, [MnIII(OO tBu)(dpaq)]+ and [MnIII(OO tBu)(dpaq2Me)]+, which utilize the anionic, amide-containing pentadentate dpaq ligand platform. These complexes were generated by reacting the corresponding MnII precursors with a large excess of tBuOOH at -15 °C in MeCN. In both cases, the corresponding mononuclear MnIII-hydroxo complexes [MnIII(OH)(dpaq)]+ and [MnIII(OH)(dpaq2Me)]+ are observed as intermediates en route to the MnIII-alkylperoxo adducts. These new MnIII-alkylperoxo complexes were characterized by electronic absorption, infrared, and Mn K-edge X-ray absorption spectroscopies. Complementary density functional theory calculations were also performed to gain insight into their bonding and structural properties. Compared to previously reported MnIII-alkylperoxo adducts, the MnIII centers in these complexes exhibit significantly altered primary coordination spheres, with a strongly donating anionic amide nitrogen located trans to the alkylperoxo moiety. This results in MnIII-alkylperoxo bonding that is dominated by σ-interactions between the alkylperoxo πip*(O-O) orbital and the Mn d z2 orbital.