Unravelling the Mechanism of CO2 Activation: Insights into Metal-Metal Cooperativity and Spin-Orbit Coupling with {3d-4f} Catalysts.

Converting CO2 into useful chemicals using metal catalysts is a significant challenge in chemistry. Among the various catalysts reported, transition metal lanthanide hybrid {3d-4f} complexes stand out for their superior efficiency and site selectivity. However, unlike transition metal catalysts, understanding the origin of this efficiency in lanthanides poses a challenge due to their orbital degeneracy, rendering the application of DFT methods ineffective. In this study, we employed a combination of density functional theory (DFT) and ab initio CASSCF/RASSI-SO calculations to explore the mechanism of CO2 conversion to cyclic carbonate using a 3d-4f heterometallic catalyst for the first time. This work unveils the importance of 3d and 4f metal cooperativity and the role of individual spin-orbit states in dictating the overall efficiency of the catalyst.

Origin of Unprecedented Formation and Reactivity of FeIV═O Species via Oxygen Activation: Role of Noncovalent Interactions and Magnetic Coupling.

Emulating the capabilities of the soluble methane monooxygenase (sMMO) enzymes, which effortlessly activate oxygen at diiron(II) centers to form a reactive diiron(IV) intermediate Q, which then performs the challenging oxidation of methane to methanol, poses a significant challenge. Very recently, one of us reported the mononuclear complex [(cyclam)FeII(CH3CN)2]2+ (1), which performed a rare bimolecular activation of the molecule of O2 to generate two molecules of FeIV═O without the requirement of external proton or electron sources, similar to sMMO. In the present study, we employed the density functional theory (DFT) calculations to investigate this unique mechanism of O2 activation. We show that secondary hydrogen-bonding interactions between ligand N-H groups and O2 play a vital role in reducing the energy barrier associated with the initial O2 binding at 1 and O-O bond cleavage to form the FeIV═O complex. Further, the unique reactivity of FeIV═O species toward simultaneous C-H and O-H bond activation process has been demonstrated. Our study unveils that the nature of the magnetic coupling between the diiron centers is also crucial. Given that the influence of magnetic coupling and noncovalent interactions in catalysis remains largely unexplored, this unexplored realm presents numerous avenues for experimental chemists to develop novel structural and functional analogues of sMMO.

Unravelling the Effect of Acid-Driven Electron Transfer in High-Valent FeIV =O/MnIV =O Species and Its Implications for Reactivity.

The electron transfer (ET) step is one of the crucial processes in biochemical redox reactions that occur in nature and has been established as a key step in dictating the reactivity of high-valent metal-oxo species. Although metalloenzymes possessing metal-oxo units at their active site are typically associated with outer-sphere electron transfer (OSET) processes, biomimetic models, in contrast, have been found to manifest either an inner-sphere electron transfer (ISET) or OSET mechanism. This distinction is clearly illustrated through the behaviour of [(N4Py)MnIV (O)]2+ (1) and [(N4Py)FeIV (O)]2+ (2) complexes, where complex 1 showcases an OSET mechanism, while complex 2 exhibits an ISET mechanism, especially evident in their reactions involving C-H bond activation and oxygen atom transfer reactions in the presence of a Lewis/Bronsted acid. However, the precise reason for this puzzling difference remains elusive. This work unveils the origin of the perplexing inner-sphere vs outer-sphere electron transfer process (ISET vs OSET) in [(N4Py)MnIV (O)]2+ (1) and [(N4Py)FeIV (O)]2+ (2) species in the presence of Bronsted acid. The calculations indicate that when the substrate (toluene) approaches both 1 and 2 that is hydrogen bonded with two HOTf molecules (denoted as 1-HOTf and 2-HOTf, respectively), proton transfer from one of the HOTf molecules to the metal-oxo unit is triggered and a simultaneous electron transfer occurs from toluene to the metal centre. Interestingly, the preference for OSET by 1-HOTf is found to originate from the choice of MnIV =O centre to abstract spin-down (ß) electron from toluene to its δ(dxy ) orbital. On the other hand, in 2-HOTf, a spin state inversion from triplet to quintet state takes place during the proton (from HOTf) coupled electron transfer (from toluene) preferring a spin-up (α) electron abstraction to its σ* (dz 2 ) orbital mediated by HOTf giving rise to ISET. In addition, 2-HOTf was calculated to possess a larger reorganisation energy, which facilitates the ISET process via the acid. The absence of spin-inversion and smaller reorganisation energy switch the mechanism to OSET for 1-HOTf. Therefore, for the first time, the significance of spin-state and spin-inversion in the electron transfer process has been identified and demonstrated within the realm of high-valent metal-oxo chemistry. This discovery holds implications for the potential involvement of high-valent Mn-oxo species in performing similar transformative processes within Photosystem II.

Probing the Origins of Puzzling Reactivity in Fe/Mn-Oxo/Hydroxo Species toward C-H Bonds: A DFT and Ab Initio Perspective.

Activation of C-H bonds using an earth-abundant metal catalyst is one of the top challenges of chemistry, where high-valent Mn/Fe-oxo(hydroxo) biomimic species play an important role. There are several open questions related to the comparative oxidative abilities of these species, and a unifying concept that could accommodate various factors influencing reactivity is lacking. To shed light on these open questions, here, we have used a combination of density functional theory (DFT) (B3LYP-D3/def2-TZVP) and ab initio (CASSCF/NEVPT2) calculations to study a series of high-valent metal-oxo species [Mn+H3buea(O/OH)] (M = Mn and Fe, n = II to V; H3buea = tris[(N'-tert-butylureaylato)-N-ethylene)]aminato towards the activation of dihydroanthracene (DHA). The H-bonding network in the ligand architecture influences the ground state-excited state gap and brings several excited states of the same spin multiplicity closer in energy, which triggers reactivity via one of those excited states, reducing the kinetic barriers for the C-H bond activation and rationalizing several puzzling reactivity trends observed in various high-valent Mn/Fe-oxo(hydroxo) species.

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.

Does the Spin State and Oriented External Electric Field Boost the Efficiency of Fe(II) Pincer Catalyst toward CO2 Hydrogenation Reaction?

In this study, we have explored the catalytic reactivities of four PNP-pincer supported Fe(II) complexes, namely, [(iPrPNMeP)FeH2(CO)] (1), [(iPrPNMeP)FeH(CO)(BH4)] (2), [(iPrPNHP)FeH2(CO)] (3), and [(iPrPNMeP)FeH(BH4)] (4) (iPrPNMeP = MeN{CH2CH2(PiPr2)}2 and iPrPNHP = HN{CH2CH2(PiPr2)}2) toward reductive CO2 hydrogenation for formate production. Our density functional theory and ab initio complete active space self-consistent field study have identified three fundamental steps in this catalytic transformation: (i) anchoring of the CO2 molecule in the vicinity of the metal using noncovalent interactions, (ii) catalyst regeneration via H2 cleavage, and (iii) formate rebound step leading to catalytic poisoning. The variations in the catalytic efficiency observed among these catalysts were attributed to either easing of steps (i) and (ii) or the hampering step (iii). This can be achieved in various chemical/non-chemical ways, for instance, (a) incorporation of strong-field ligands such as CO facilitating single-state reactivity and eliminating two-state reactivity that generally enhances the rate and (b) inclusion of Lewis acids such as LiOTf and strong bases found to either avoid catalytic poisoning or ease the H-H cleavages, to enhance the rate of reaction (c) evading mixing of excited open-shell singlet states to the ground closed-shell singlet state that hampers the catalytic regeneration. We have probed the role of oriented external electric fields (OEEFs) in the entire mechanistic profile for the best and worst catalyst, and our study suggests that imposing OEEFs opposite to the reaction axis (z-axis) fastens the catalytic regeneration step and, at the same time, hampers catalytic poisoning. The application of OEEFs is found to regulate the energetics of various spin states and can hamper two-state reactivity, therefore increasing the efficiency. Thus, this study provides insights into the CO2 hydrogenation mechanism where the role of bases/Lewis acid, ligand design, spin states, and electric field in a particular direction has been established and is, therefore, likely to pave the way forward for a new generation of catalysts.

Can you break the oxo-wall? A multiconfigurational perspective.

The concept of the "oxo-wall" was conceived about 60 years ago by Harry B. Gray, and has been found to be related to the non-existence of high-valent M-oxo species in the +IV oxidation state in a tetragonal geometry beyond group 8 in the periodic table. Several efforts have been made in the past decades to test and find examples that violate this theory. Several claims of violation in the past were attributed to the difference in the geometries/coordination number and, therefore, these are not examples of true violation. In recent years, substantial efforts have been undertaken to synthesise a true CoIVO species with various ligand architectures. CoIVO and CoIII-O˙ are electromers and, while they are interchangeably used in the literature; the former violates the oxo-wall while the latter does not. The possibility that these two species could exist in various proportions similar to resonating structures has not been considered in detail in this area. Furthermore, there have been no attempts to quantify such mixing. In this direction, we have employed density functional theory (DFT) and ab initio CASSCF/NEVPT2 methods to quantify the co-existence of CoIVO and CoIII-O˙ isomeric species. By thoroughly studying six different metal-oxo species, we affirm that the nature of such electromeric mixing is minimal/negligible for FeIVO and MnIVO species - both are pre-oxo-wall examples. By studying four different ligand architectures with Co-oxo species, our results unveil that the mixing of CoIVO ↔ CoIII-O˙ is substantial in all geometries, with dominant CoIVO species favourable for the S = 3/2 intermediate spin state. The percentage of the CoIII-O˙ species is enhanced substantially for the S = 1/2 low-spin state. We have attempted to develop a tool to estimate the percentage of the CoIII-O˙ species using various structural parameters. Among those tested, a linear relationship between % of CoIII-O˙ and a bond length based ratio is found (, where d(Co-O) and d(Co-Nax) are the axial Co-O and Co-Nax bond lengths in Å, respectively). It is found that the higher the Rd, the greater the CoIII-O˙ character will be and the geometrically portable correlation developed offers a way to qualitatively compute the % of CoIII-O˙ character for unknown geometries.

Arjunetin as a promising drug candidate against SARS-CoV-2: molecular dynamics simulation studies.

Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, -8.4 kcal/mol; PLpro, -7.6 kcal/mol and RdRp, -8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, -7.2 kcal/mole and PLpro -7.7 kcal/mole) and Remdesivir (RdRp -7.6 kcal/mole). To further investigate this, we performed 200-500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19.Communicated by Ramaswamy H. Sarma.

Are lanthanide-transition metal direct bonds a route to achieving new generation {3d-4f} SMMs?

Lanthanide based single-molecule magnets are gaining wide attention due to their potential applications in emerging technologies. One of the main challenges in this area is quenching quantum tunnelling of magnetisation (QTM), which often undercuts the magnetisation reversal barrier. Among the several strategies employed, enhancing exchange coupling has been studied in detail, with large exchanges resulting in stronger quenching of QTM effects. Lanthanides, however, suffer from weak exchanges offered by the deeply buried 4f orbitals and the numerous attempts to enhance the exchange coupling in the {3d-4f} pairs have not exceeded values larger than 30 cm-1. In this work, using a combination of DFT and the ab initio CASSCF/RASSI-SO method, we have explored lanthanide-transition metal direct bonds as a tool to quench QTM effects. In this direction, we have modelled [PyCp2LnMCp(CO)2] (Ln = Gd(III), Dy(III), and Er(III) and M = V(0), Mn(0), Co(0) and Fe(I) and here PyCp2 = [2,6-(CH2C5H3)2C5H3N]2- using [PyCp2DyFeCp(CO)2] as an example as reported by Nippe et al. (C. P. Burns, X. Yang, J. D. Wofford, N. S. Bhuvanesh, M. B. Hall and M. Nippe, Angew. Chem., Int. Ed. 2018, 57, 8144). Bonding analysis reveals a dative Ln-TM bond with a donation of π(V/Mndxy-π*CO) to 5dz2 (Gd) in the case of Gd-V and Gd-Mn and 4s(Co) to 5dxy/5dyz (Gd) for Gd-Co with the transition metal ion being found in the low-spin S = ½ configurations in all the cases. B3LYP/TZV (Gd;CSDZ) calculations on [PyCp2GdMCp(CO)2] yield JGd-V = -46.1 cm-1, JGd-Mn = -57.1 cm-1, JGd-Co = +55.3 cm-1, JGd-Fe+ = +13.9 cm-1, JGd-Vhs = -162.1 cm-1 and JGd-Mnhs = -343.9 cm-1 and unveiling record-high J values for {3d-4f} complexes. The mechanism of magnetic coupling is developed, which discloses the dominating presence of strong 3d-4f orbital overlaps in most of the cases studied, leading to antiferromagnetic exchange. When these overlaps are weaker and 3d to Gd(5dz2), charge transfer dominates, yielding a ferromagnetic coupling for the Gd-Co/Gd-Fe+ complexes. Calculations performed on the anisotropic Dy(III) and Er(III) complexes reveal that the ground state gzz axis lies along the Cp-Ln-Cp axis and the Ln-TM bonds, respectively. Thus the Ln-TM bond hinders the single-ion anisotropy of Dy(III) by offering equatorial ligation and lowering the mJ = ±½ state energy, and at the same time, helping in enhancing the axiality of Er(III). When strong {3d-4f} exchange couplings are introduced, record-high barrier heights as high as 229 cm-1 were accomplished. Furthermore, the exchange coupling annihilates the QTM effects and suggests the lanthanide-transition metal direct bond as a viable alternative to enhance exchange coupling to bring {3d-4f} complexes back in the race for high-blocking SMMs.

Insights into the Dual Shuttle Catalytic Mechanism of Guanine Deaminase.

Guanine deaminases (GD) are essential enzymes that help in regulating the nucleobase pool. Since the deamination reaction can result in the accumulation of mutagenic bases that can lead to genomic instability, these enzymes are tightly regulated and are nonpromiscuous. Here, we delineate the basis of their substrate fidelity via entailing the reaction mechanism of deamination by employing density functional theory (DFT) calculations on NE0047, a GD from Nitrosomonas europaea. The results show that, unlike pyrimidine deaminases, which require a single glutamic acid as a proton shuttle, GDs involve two amino acids, E79 and E143 (numbering in NE0047), which control its reactivity. The hybrid quantum mechanics/molecular mechanics (QM/MM) calculations have shown that the first Zn-bound proton transfer to the N3 atom of the substrate is mediated by the E79 residue, and the second proton is transferred to the amine nitrogen of substrate via E143. Moreover, cluster models reveal that the crystallographic water molecules near the active site control the reactivity. A comparison with human GD reveals that the proposed catalytic mechanism is generic, and the knowledge generated here can be effectively applied to design selective inhibitors.

Deciphering the mechanism of oxygen atom transfer by non-heme MnIV-oxo species: an ab initio and DFT exploration.

Oxygen atom transfer (OAT) reactions employing transition metal-oxo species have tremendous significance in homogeneous catalysis for industrial use. Understanding the structural and mechanistic aspects of OAT reactions using high-valent metal-oxo species is of great importance to fine-tune their reactivity. Herein we examine the reactivity of a non-heme high-valent oxo-manganese(iv) complex, [MnIVH3buea(O)]- towards a variety of substrates such as PPh2Me, PPhMe2, PCy3, PPh3, and PMe3 using density functional theory as well as ab initio CASSCF/NEVPT2 methods. We have initially explored the structure and bonding of [MnIVH3buea(O)]- and its congener [MnIVH3buea(S)]-. Our calculations affirm an S = 3/2 ground state of the catalyst with the S = 5/2 and S = 1/2 excited states predicted to be too high lying in energy to participate in the reaction mechanism. Our ab initio CASSCF/NEVPT2 calculations, however, reveal a strong multi-reference character for the ground S = 3/2 state with many low-lying quartets mixing significantly with the ground state. This opens up various reaction channels, and the admixed wave-function evolves during the reaction with the excited triplet dominating the ground state wave-function at the reactant complex. Our calculations predict the following pattern of reactivity, PCy3 < PMe3 < PPh3 < PPhMe2 < PPh2Me for the OAT reaction with the MnIV[double bond, length as m-dash]O species which correlates well with the experimental observations. Detailed electronic structure analysis of the transitions states reveal that these substrates react via an unusual low-energy δ-type pathway where a spin-up electron from the substrate is transferred to the δ*x2-y2 orbital of the MnIV[double bond, length as m-dash]O facilitated by its multi-reference character. The unusual reactivity observed here has implications in understanding the reactivity of [Mn4Ca] species in photosystem II.

Selective C-H halogenation over hydroxylation by non-heme iron(iv)-oxo.

Non-heme iron based halogenase enzymes promote selective halogenation of the sp3-C-H bond through iron(iv)-oxo-halide active species. During halogenation, competitive hydroxylation can be prevented completely in enzymatic systems. However, synthetic iron(iv)-oxo-halide intermediates often result in a mixture of halogenation and hydroxylation products. In this report, we have developed a new synthetic strategy by employing non-heme iron based complexes for selective sp3-C-H halogenation by overriding hydroxylation. A room temperature stable, iron(iv)-oxo complex, [Fe(2PyN2Q)(O)]2+ was directed for hydrogen atom abstraction (HAA) from aliphatic substrates and the iron(ii)-halide [FeII(2PyN2Q)(X)]+ (X, halogen) was exploited in conjunction to deliver the halogen atom to the ensuing carbon centered radical. Despite iron(iv)-oxo being an effective promoter of hydroxylation of aliphatic substrates, the perfect interplay of HAA and halogen atom transfer in this work leads to the halogenation product selectively by diverting the hydroxylation pathway. Experimental studies outline the mechanistic details of the iron(iv)-oxo mediated halogenation reactions. A kinetic isotope study between PhCH3 and C6D5CD3 showed a value of 13.5 that supports the initial HAA step as the RDS during halogenation. Successful implementation of this new strategy led to the establishment of a functional mimic of non-heme halogenase enzymes with an excellent selectivity for halogenation over hydroxylation. Detailed theoretical studies based on density functional methods reveal how the small difference in the ligand design leads to a large difference in the electronic structure of the [Fe(2PyN2Q)(O)]2+ species. Both experimental and computational studies suggest that the halide rebound process of the cage escaped radical with iron(iii)-halide is energetically favorable compared to iron(iii)-hydroxide and it brings in selective formation of halogenation products over hydroxylation.