Correlating Structure with Spectroscopy in Ascorbate Peroxidase Compound II.

Structural and spectroscopic investigations of compound II in ascorbate peroxidase (APX) have yielded conflicting conclusions regarding the protonation state of the crucial Fe(IV) intermediate. Neutron diffraction and crystallographic data support an iron(IV)-hydroxo formulation, whereas Mössbauer, X-ray absorption (XAS), and nuclear resonance vibrational spectroscopy (NRVS) studies appear consistent with an iron(IV)-oxo species. Here we examine APX with spectroscopy-oriented QM/MM calculations and extensive exploration of the conformational space for both possible formulations of compound II. We establish that irrespective of variations in the orientation of a vicinal arginine residue and potential reorganization of proximal water molecules and hydrogen bonding, the Fe-O distances for the oxo and hydroxo forms consistently fall within distinct, narrow, and nonoverlapping ranges. The accuracy of geometric parameters is validated by coupled-cluster calculations with the domain-based local pair natural orbital approach, DLPNO-CCSD(T). QM/MM calculations of spectroscopic properties are conducted for all structural variants, encompassing Mössbauer, optical, X-ray absorption, and X-ray emission spectroscopies and NRVS. All spectroscopic observations can be assigned uniquely to an Fe(IV)═O form. A terminal hydroxy group cannot be reconciled with the spectroscopic data. Under no conditions can the Fe(IV)═O distance be sufficiently elongated to approach the crystallographically reported Fe-O distance. The latter is consistent only with a hydroxo species, either Fe(IV) or Fe(III). Our findings strongly support the Fe(IV)═O formulation of APX-II and highlight unresolved discrepancies in the nature of samples used across different experimental studies.

C-H bond activation by high-valent iron/cobalt-oxo complexes: a quantum chemical modeling approach.

High-valent metal-oxo species serve as key intermediates in the activation of inert C-H bonds. Here, we present a comprehensive DFT analysis of the parameters that have been proposed as influencing factors in modeled high-valent metal-oxo mediated C-H activation reactions. Our approach involves utilizing DFT calculations to explore the electronic structures of modeled FeIVO (species 1) and CoIVO ↔ CoIII-O˙ (species 2), scrutinizing their capacity to predict improved catalytic activity. DFT and DLPNO-CCSD(T) calculations predict that the iron-oxo species possesses a triplet as the ground state, while the cobalt-oxo has a doublet as the ground state. Furthermore, we have investigated the mechanistic pathways for the first C-H bond activation, as well as the desaturation of the alkanes. The mechanism was determined to be a two-step process, wherein the first hydrogen atom abstraction (HAA) represents the rate-limiting step, involving the proton-coupled electron transfer (PCET) process. However, we found that the second HAA step is highly exothermic for both species. Our calculations suggest that the iron-oxo species (Fe-O = 1.672 Å) exhibit relatively sluggish behavior compared to the cobalt-oxo species (Co-O = 1.854 Å) in C-H bond activation, attributed to a weak metal-oxygen bond. MO, NBO, and deformation energy analysis reveal the importance of weakening the M-O bond in the cobalt species, thereby reducing the overall barrier to the reaction. This catalyst was found to have a C-H activation barrier relatively smaller than that previously reported in the literature.

Nitric Oxide Oxygenation Reactions of Cobalt-Peroxo and Cobalt-Nitrosyl Complexes.

Here, we report a comparative study of nitric oxide oxidation (NOO) reactions of CoIII-peroxo (CoIII-O22-) and Co-nitrosyl ({CoNO}8) complexes bearing the same N4-donor ligand (HMTETA) framework. In this regard, we prepared and characterized two new [(HMTETA)CoIII(O22-)]+ (2, S = 2) and [(HMTETA)Co(NO)]2+ (3, S = 1) complexes from [(HMTETA)CoII(CH3CN)2]2+ (1). Both complexes (2 and 3) are characterized by different spectroscopic measurements, including their DFT-optimized structures. Complex 2 produces CoII-nitrato [(HMTETA)CoII(NO3-)]+ (CoII-NO3-, 4) complex in the presence of NO. In contrast, when 3 reacted with a superoxide (O2•-) anion, it generated CoII-nitrito [(HMTETA)CoII(NO2-)]+ (CoII-NO2-, 5) with O2 evolution. Experiments performed using 18/16O-labeled superoxide (18O2•-/16O2•-) showed that O2 originated from the O2•- anion. Both the NOO reactions are believed to proceed via a presumed peroxynitrite (PN) intermediate. Although we did not get direct spectral evidence for the proposed PN species, the mechanistic investigation using 2,4-di-tert-butylphenol indirectly suggests the formation of a PN intermediate. Furthermore, tracking the source of the N-atom in the above NOO reactions using 15N-labeled nitrogen (15NO) revealed N-atoms in 4 (CoII-15NO3-) and 5 (CoII-15NO2-) derived from the 15NO moiety.

Mechanism of Hydroboration of CO2 Using an Fe Catalyst: What Controls the Reactivity and Product Selectivity?

Using a combination of density functional theory (DFT) and ab initio complete active space self-consistent field (CASSCF) calculations, various elementary steps in the mechanism of the reductive hydroboration of CO2 to two-electron-reduced boryl formate, four-electron-reduced bis(boryl)acetal, and six-electron-reduced methoxy borane by the [Fe(H)2(dmpe)2] catalyst were established. The replacement of hydride by oxygen ligation after the boryl formate insertion step is the rate-determining step. Our work unveils, for the first time, (i) how a substrate steers product selectivity in this reaction and (ii) the importance of configurational mixing in contracting the kinetic barrier heights. Based on the reaction mechanism established, we have further focused on the effect of other metals, such as Mn and Co, on rate-determining steps and on catalyst regeneration.

Comparative oxidative ability of mononuclear and dinuclear high-valent iron-oxo species towards the activation of methane: does the axial/bridge atom modulate the reactivity?

Over the years, mononuclear FeIVO species have been extensively studied, but the presence of dinuclear FeIVO species in soluble methane monooxygenase (sMMO) has inspired the development of biomimic models that could activate inert substrates such as methane. There are some successful attempts; particularly the [(Por)(m-CBA) FeIV(µ-N)FeIV(O)(Por˙+)]- species has been reported to activate methane and yield decent catalytic turnover numbers and therefore regarded as the closest to the sMMO enzyme functional model, as no mononuclear FeIVO analogues could achieve this feat. In this work, we have studied a series of mono and dinuclear models using DFT and ab initio DLPNO-CCSD(T) calculations to probe the importance of nuclearity in enhancing the reactivity. We have probed the catalytic activities of four complexes: [(HO)FeIV(O)(Por)]- (1), [(HO)FeIV(O)(Por˙+)] (2), µ-oxo dinuclear iron species [(Por)(m-CBA)FeIV(µ-O)FeIV(O) (Por˙+)]- (3) and N-bridged dinuclear iron species [(Por)(m-CBA)FeIV(µ-N)FeIV(O)(Por˙+)]- (4) towards the activation of methane. Additionally, calculations were performed on the mononuclear models [(X)FeIV(O)(Por˙+)]n {X = N 4a (n = -2), NH 4b (n = -1) and NH24c (n = 0)} to understand the role of nuclearity in the reactivity. DFT calculations performed on species 1-4 suggest an interesting variation among them, with species 1-3 possessing an intermediate spin (S = 1) as a ground state and species 4 possessing a high-spin (S = 2) as a ground state. Furthermore, the two FeIV centres in species 3 and 4 are antiferromagnetically coupled, yielding a singlet state with a distinct difference in their electronic structure. On the other hand, species 2 exhibits a ferromagnetic coupling between the FeIV and the Por˙+ moiety. Our calculations suggest that the higher barriers for the C-H bond activation of methane and the rebound step for species 1 and 3 are very high in energy, rendering them unreactive towards methane, while species 2 and 4 have lower barriers, suggesting their reactivity towards methane. Studies on the system reveal that model 4a has multiple FeN bonds facilitating greater reactivity, whereas the other two models have longer Fe-N bonds and less radical character with steeper barriers. Strong electronic cooperativity is found to be facilitated by the bridging nitride atom, and this cooperativity is suppressed by substituents such as oxygen, rendering them inactive. Thus, our study unravels that apart from enhancing the nuclearity, bridging atoms that facilitate strong cooperation between the metals are required to activate very inert substrates such as methane, and our results are broadly in agreement with earlier experimental findings.

Electronic, geometrical and photophysical facets of five coordinated porphyrin N-heterocyclic carbene transition metals complexes: A theoretical study.

In the realm of dye sensitized solar cells (DSSCs), the 3d transition metals as photosensitizers are scarcely studied. In the present work, electronic structures, FMO, MEP surfaces, NBO analysis, energetics and photophysical properties of earth abundant metals (Mn, Fe and Co) based metalloporphyrins coordinated with NHC-carbene have been explored by using DFT and TDDFT calculations. According to formation energies and energy decomposition analysis (EDA), the cobalt based metalloporphyrins species are found to be more stable while in contrast manganese based species are predicted as more reactive among all. Also, from the ligation point of view, the TPP (meso-tetraphenylporphyrin) ligand forms more steady and rigid coordination as compare to the TTP (meso-tetratolylporphyrin) ligand. FMO analysis also support these observations. NBO and SNO results support the electronic configurations as well as unveil the controversial bonding pattern of NHCcarbon and metal atom and found that there is σ-bonding present between the metal and the NHCcarbon by the overlapping of sp-hybridized orbitals of carbenecarbon and sp/d hybrid orbital of the metal atom. TDDFT results show that the highest light harvesting efficiency (LHE) of all the studied species is found under the range of 360 nm - 380 nm (λ) and this may due to the presence of longer π-conjugations. In-depth investigation of this work may help to design new robust energy harvesting systems for high energy conversion efficiency based on earth abundance metals. Our results are in well agreement with the available experimental findings.

Electronic structures, bonding aspects and spectroscopic parameters of homo/hetero valent bridged dinuclear transition metal complexes.

Bridged dinuclear metal complexes have fascinated scientists worldwide, and remarkable success has been achieved to unravel the electronic structures, structure-function relationship, coordination environments, and fine mechanistic details of the enzymes owing to the repercussion of biomimetic studies carried out on dinuclear model systems. Molecular level study of these systems integrated with spectroscopic study helps in gaining deep insights about structural and electronic aspects of natural enzymatic systems. Considering the same, here first time we report DFT study on bridged non-heme metal complexes based on N-Et-HPTB ligand system containing homovalent (MIIMII); {[(MnII)2(O2CCH3)(N-Et-HPTB)]2+; Species I), [(FeII)2(O2CCH3)(N-Et-HPTB)]2+; Species II), [(CoII)2(O2CCH3)(N-Et-HPTB)]2+; Species III)} and heterovalent (MIIIMII): {[(MnIII)(MnII)(O2)(N-Et-HPTB)]2+; Species Ia) [(FeIII)(FeII)(O2)(N-Et-HPTB)]2+; Species IIa) and [(CoIII)(CoII)(O2)(N-Et-HPTB)]2+; Species IIIa)} dinuclear metal centres. Bridging oxygen bears a significant spin density which may prompt important chemical reactions involving activation of bonds like C-H/O-H/N-H etc. TD-DFT calculations for UV-Visible absorption have been carried out to further shed light on structural-functional and electronic structures of these dinuclear species. Studying these dinuclear species may be a good starting point for the study of active sites of the bimetallic centre of dinuclear enzymes and thus may serve as fascinating spectroscopic models. Further, FMO analysis, MEP mapping, and NBO calculations were employed to analyze bonding aspects predict theoretical reactivity behaviour and any kind of stabilizing interactions present in the reported species.

Role of Coordination Geometry on the Magnetic Relaxation Dynamics of Isomeric Five-Coordinate Low-Spin Co(II) Complexes.

To investigate the influence of the coordination geometry on the magnetization relaxation dynamics, two geometric isomers of a five-coordinate low-spin Co(II) complex with the general molecular formula [Co(DPPE)2Cl]SnCl3 (DPPE = diphenylphosphinoethane) were synthesized and structurally characterized. While one isomer has a square pyramidal geometry (Co-SP (1)), the other isomer figures a trigonal bipyramidal geometry (Co-TBP (2)). Both complexes were already reported elsewhere. The spin state of these complexes is unambiguously determined by detailed direct current (dc) magnetic data, X-band, and high-frequency EPR measurements. Slow relaxation of magnetization is commonly observed for systems with S > 1/2. However, both 1 and 2 show field-induced slow relaxation of magnetization. Especially 1 shows relaxation times up to τ = 35 ms at T = 1.8 K, which is much longer than the reported values for undiluted Co(II) low-spin monomers. In 2, the maximal field-induced relaxation time is suppressed to τ = 5 ms. We attribute this to the change in g-anisotropy, which is, in turn, correlated to the spatial arrangement of ligands (i.e., coordination geometry) around the Co(II) ions. Besides the detailed electronic structure of these complexes, the experimental observations are further corroborated by theoretical calculations.

Novel {Cu4} and {Cu4Cd6} clusters derived from flexible aminoalcohols: synthesis, characterization, crystal structures, and evaluation of anticancer properties.

Two new copper clusters, {Cu4} and {Cu4Cd6}, with polydentate aminoalcohol ligands, diethanol propanolamine (H3L1) and bis-tris{2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol} (H6L2), have been synthesized under mild conditions and characterized thoroughly by single-crystal X-ray diffraction (XRD), infrared spectroscopy, elemental analysis, powder XRD, magnetic and DFT studies, and absorption and fluorescence spectroscopy. The cluster {Cu4} exhibits a rare tetranuclear copper cubane core whereas {Cu4Cd6} forms an unusual heterometallic cage owing to the introduction of the second metal Cd into the ligand. A hexapodal ligand (H6L2) with N and O donor atoms was chosen deliberately for the construction of a high-nuclearity cluster, i.e., {Cu4Cd6}. Interestingly, both the clusters displayed significant cytotoxicity towards human cervical (HeLa) and lung (A549) cancer cells as evident from the shallow IC50 values [15.6 ± 0.8 µM (HeLa), 18.5 ± 1.9 µM (A549) for {Cu4}, and 11.1 ± 1.5 µM (HeLa), 10.2 ± 1.3 µM (A549) for {Cu4Cd6}] obtained after a 24 h incubation. However, moderate toxicity was observed toward immortalized lung epithelial normal cells (HPL1D) with IC50 values of 32.4 ± 1.2 µM for {Cu4} and 27.6 ± 1.7 µM for {Cu4Cd6}. A cellular apoptotic study using HeLa cells revealed that the {Cu4} cluster triggered apoptosis at both the early and late phases while the {Cu4Cd6} cluster facilitate apoptosis mainly at the late apoptotic stage. A standard 2',7'-dichlorodihydrofluorescein-diacetate (DCFH-DA) test affirms that both the clusters enhanced ROS production inside the cancer cells, responsible for promoting cell apoptosis. The decanuclear {Cu4Cd6} clusters demonstrated better anticancer activity compared to the tetranuclear {Cu4} clusters, indicating the role of high nuclearity and additional Cd metal in the enhanced intracellular production of ROS.

Ligand-Constraint-Induced Peroxide Activation for Electrophilic Reactivity.

µ-1,2-peroxo-bridged diiron(III) intermediates P are proposed as reactive intermediates in various biological oxidation reactions. In sMMO, P acts as an electrophile, and performs hydrogen atom and oxygen atom transfers to electron-rich substrates. In cyanobacterial ADO, however, P is postulated to react by nucleophilic attack on electrophilic carbon atoms. In biomimetic studies, the ability of µ-1,2-peroxo-bridged dimetal complexes of Fe, Co, Ni and Cu to act as nucleophiles that effect deformylation of aldehydes is documented. By performing reactivity and theoretical studies on an end-on µ-1,2-peroxodicobalt(III) complex 1 involving a non-heme ligand system, L1, supported on a Sn6 O6 stannoxane core, we now show that a peroxo-bridged dimetal complex can also be a reactive electrophile. The observed electrophilic chemistry, which is induced by the constraints provided by the Sn6 O6 core, represents a new domain for metal-peroxide reactivity.

Effect of the Ligand Backbone on the Reactivity and Mechanistic Paradigm of Non-Heme Iron(IV)-Oxo during Olefin Epoxidation.

The oxygen atom transfer (OAT) reactivity of the non-heme [FeIV (2PyN2Q)(O)]2+ (2) containing the sterically bulky quinoline-pyridine pentadentate ligand (2PyN2Q) has been thoroughly studied with different olefins. The ferryl-oxo complex 2 shows excellent OAT reactivity during epoxidations. The steric encumbrance and electronic effect of the ligand influence the mechanistic shuttle between OAT pathway I and isomerization pathway II (during the reaction stereo pure olefins), resulting in a mixture of cis-trans epoxide products. In contrast, the sterically less hindered and electronically different [FeIV (N4Py)(O)]2+ (1) provides only cis-stilbene epoxide. A Hammett study suggests the role of dominant inductive electronic along with minor resonance effect during electron transfer from olefin to 2 in the rate-limiting step. Additionally, a computational study supports the involvement of stepwise pathways during olefin epoxidation. The ferryl bend due to the bulkier ligand incorporation leads to destabilization of both dz2 and dx2-y2 orbitals, leading to a very small quintet-triplet gap and enhanced reactivity for 2 compared to 1. Thus, the present study unveils the role of steric and electronic effects of the ligand towards mechanistic modification during olefin epoxidation.

Deciphering the origin of million-fold reactivity observed for the open core diiron [HO-FeIII-O-FeIV[double bond, length as m-dash]O]2+ species towards C-H bond activation: role of spin-states, spin-coupling, and spin-cooperation.

High-valent metal-oxo species have been characterised as key intermediates in both heme and non-heme enzymes that are found to perform efficient aliphatic hydroxylation, epoxidation, halogenation, and dehydrogenation reactions. Several biomimetic model complexes have been synthesised over the years to mimic both the structure and function of metalloenzymes. The diamond-core [Fe2(µ-O)2] is one of the celebrated models in this context as this has been proposed as the catalytically active species in soluble methane monooxygenase enzymes (sMMO), which perform the challenging chemical conversion of methane to methanol at ease. In this context, a report of open core [HO(L)FeIII-O-FeIV(O)(L)]2+ (1) gains attention as this activates C-H bonds a million-fold faster compared to the diamond-core structure and has the dual catalytic ability to perform hydroxylation as well as desaturation with organic substrates. In this study, we have employed density functional methods to probe the origin of the very high reactivity observed for this complex and also to shed light on how this complex performs efficient hydroxylation and desaturation of alkanes. By modelling fifteen possible spin-states for 1 that could potentially participate in the reaction mechanism, our calculations reveal a doublet ground state for 1 arising from antiferromagnetic coupling between the quartet FeIV centre and the sextet FeIII centre, which regulates the reactivity of this species. The unusual stabilisation of the high-spin ground state for FeIV[double bond, length as m-dash]O is due to the strong overlap of with the orbital, reducing the antibonding interactions via spin-cooperation. The electronic structure features computed for 1 are consistent with experiments offering confidence in the methodology chosen. Further, we have probed various mechanistic pathways for the C-H bond activation as well as -OH rebound/desaturation of alkanes. An extremely small barrier height computed for the first hydrogen atom abstraction by the terminal FeIV[double bond, length as m-dash]O unit was found to be responsible for the million-fold activation observed in the experiments. The barrier height computed for -OH rebound by the FeIII-OH unit is also smaller suggesting a facile hydroxylation of organic substrates by 1. A strong spin-cooperation between the two iron centres also reduces the barrier for second hydrogen atom abstraction, thus making the desaturation pathway competitive. Both the spin-state as well as spin-coupling between the two metal centres play a crucial role in dictating the reactivity for species 1. By exploring various mechanistic pathways, our study unveils the fact that the bridged µ-oxo group is a poor electrophile for both C-H activation as well for -OH rebound. As more and more evidence is gathered in recent years for the open core geometry of sMMO enzymes, the idea of enhancing the reactivity via an open-core motif has far-reaching consequences.

Expanding the limits of catalysts with low-valent main-group elements for the hydroboration of aldehydes and ketones using [L†Sn(ii)][OTf] (L† = aminotroponate; OTf = triflate).

A triflatostannylene [L†Sn(ii)][OTf] (2) is reported here as an efficient catalyst with low-valent main-group element for the hydroboration of aldehydes and ketones (L† = aminotroponate). Using 0.025-0.25 mol% of compound 2, hydroboration of various aldehydes and ketones is accomplished in 0.13-1.25 h at room temperature; the aliphatic aldehydes show an impressive TOF of around 30 000 h-1. DFT calculations are performed to explore the mechanistic aspects of this reaction suggesting that the reaction proceeds via a stepwise pathway with hydridostannylene [L†Sn(ii)H] (2a) as the active catalyst and the H atom transfer from the Sn-H bond to the carbonyl carbon being the rate determining step.

Interplay of Electronic Cooperativity and Exchange Coupling in Regulating the Reactivity of Diiron(IV)-oxo Complexes towards C-H and O-H Bond Activation.

Activation of inert C-H bonds such as those of methane are extremely challenging for chemists but in nature, the soluble methane monooxygenase (sMMO) enzyme readily oxidizes methane to methanol by using a diiron(IV) species. This has prompted chemists to look for similar model systems. Recently, a (µ-oxo)bis(µ-carboxamido)diiron(IV) ([FeIV2 O(L)2 ]2+ L=N,N-bis-(3',5'-dimethyl-4'-methoxypyridyl-2'-methyl)-N'-acetyl-1,2-diaminoethane) complex has been generated by bulk electrolysis and this species activates inert C-H bonds almost 1000 times faster than mononuclear FeIV =O species and at the same time selectively activates O-H bonds of alcohols. The very high reactivity and selectivity of this species is puzzling and herein we use extensive DFT calculations to shed light on this aspect. We have studied the electronic and spectral features of diiron {FeIII -µ(O)-FeIII }+2 (complex I), {FeIII -µ(O)-FeIV }+3 (II), and {FeIV -µ(O)-FeIV }+4 (III) complexes. Strong antiferromagnetic coupling between the Fe centers leads to spin-coupled S=0, S=3/2, and S=0 ground state for species I-III respectively. The mechanistic study of the C-H and O-H bond activation reveals a multistate reactivity scenario where C-H bond activation is found to occur through the S=4 spin-coupled state corresponding to the high-spin state of individual FeIV centers. The O-H bond activation on the other hand, occurs through the S=2 spin-coupled state corresponding to an intermediate state of individual FeIV centers. Molecular orbital analysis reveals σ-π/π-π channels for the reactivity. The nature of the magnetic exchange interaction is found to be switched during the course of the reaction and this offers lower energy pathways. Significant electronic cooperativity between two metal centers during the course of the reaction has been witnessed and this uncovers the reason behind the efficiency and selectivity observed. The catalyst is found to prudently choose the desired spin states based on the nature of the substrate to effect the catalytic transformations. These findings suggest that the presence of such factors play a role in the reactivity of dinuclear metalloenzymes such as sMMO.

Oxidation of methane by an N-bridged high-valent diiron-oxo species: electronic structure implications on the reactivity.

High-valent iron-oxo species are key intermediates in C-H bond activation of several substrates including alkanes. The biomimic heme and non-heme mononuclear Fe(IV)=O complexes are very popular in this area and have been thoroughly studied over the years. These species despite possessing aggressive catalytic ability, cannot easily activate inert C-H bonds such as those of methane. In this context dinuclear complexes have gained attention, particularly µ-nitrido dinuclear iron species [(TPP)(m-CBA)Fe(IV)(µ-N)Fe(IV)(O)(TPP(˙+))](-) reported lately exhibits remarkable catalytic abilities towards substrates such as methane. Here using DFT methods, we have explored the electronic structure and complex spin-state energetics present in this species. To gain insights into the nature of bonding, we have computed the absorption, the EPR and the Mössbauer parameters and have probed the mechanism of methane oxidation by the dinuclear Fe(IV)=O species. Calculated results are in agreement with the experimental data and our calculations predict that in [(TPP)(m-CBA)Fe(IV)(µ-N)Fe(IV)(O)(TPP(˙+))](-)species, the two high-spin iron centres are antiferromagnetically coupled leading to a doublet ground state. Our calculations estimate an extremely low kinetic barrier of 26.6 kJ mol(-1) (at doublet surface) for the C-H bond activation of methane by the dinuclear Fe(IV)=O species. Besides these mechanistic studies on the methane activation reveal the unique electronic cooperativity present in this type of dinuclear complex and unravel the key question of why mononuclear analogues are unable to perform such reactions.