Sextet Spin States Research Articles

Hydrogen-Bond-Assisted Catalysis: Hydroxylation of Paclitaxel by Human CYP2C8.

Paclitaxel (PTX, or Taxol), a chemotherapeutic agent widely employed in the treatment of various cancers, undergoes metabolic transformations through the cytochrome P450 enzymes CYP3A4 and CYP2C8. CYP3A4 catalyzes the aromatic hydroxylation reaction of PTX, whereas CYP2C8 demonstrates a distinct reactivity pattern, producing 6α-hydroxypaclitaxel via alkane hydroxylation. Despite the significant impact of PTX metabolism on its anticancer efficacy, the detailed mechanisms underlying these transformations have remained largely unclear. In this study, we employed hybrid quantum mechanics and molecular mechanics (QM/MM) calculations to elucidate the mechanism of PTX metabolism by human CYP2C8. Our QM/MM results reveal that the hydroxylation of PTX by CYP2C8 follows an atypical rebound mechanism. Either of the two hydrogen atoms at the C6 position of PTX can be abstracted, leading to a common radical intermediate. Although the subsequent rebound barrier is unusually high, stereochemical scrambling is unlikely, as the rebound barrier for the formation of the 6α-hydroxylated PTX─the actual product─is significantly lower than that for the 6β-hydroxylated metabolite. Thus, product selectivity is determined by the non-rate-determining rebound step. Furthermore, the hydroxyl group at the C7 position of PTX plays a catalytic role by facilitating the hydrogen abstraction and rebound steps. Our study also confirms a pronounced stability of the transition state in the high-spin sextet spin state, enabled by the enzyme's specific substrate positioning.

Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model

Previous studies on biocatalytic transformations of pinenes by cytochrome P450 (CYP) enzymes reveal the formation of different oxygenated products from a single substrate due to the multistate reactivity of CYP and the many reactive sites in the pinene scaffold. Up until now, the detailed mechanism of these biocatalytic transformations of pinenes have not been reported. Hereby, we report a systematic theoretical study of the plausible hydrogen abstraction and hydroxylation reactions of α- and β-pinenes by CYP using the density functional theory (DFT) method. All DFT calculations in this study were based on B3LYP/LAN computational methodology using the Gaussian09 software. We used the B3LYP functional with corrections for dispersive forces, BSSE, and anharmonicity to study the mechanism and thermodynamic properties of these reactions using a bare model (without CYP) and a pinene-CYP model. According to the potential energy surface and Boltzmann distribution for radical conformers, the major reaction products of CYP-catalyzed hydrogen abstraction from β-pinene are the doublet trans (53.4%) and doublet cis (46.1%) radical conformer at delta site. The formation of doublet cis/trans hydroxylated products released a total Gibbs free energy of about 48 kcal/mol. As for alpha pinene, the most stable radicals were trans-doublet (86.4%) and cis-doublet (13.6%) at epsilon sites, and their hydroxylation products released a total of ~50 kcal/mol Gibbs free energy. Our results highlight the likely C-H abstraction and oxygen rebounding sites accounting for the multi-state of CYP (doublet, quartet, and sextet spin states) and the formation of different conformers due to the presence of cis/trans allylic hydrogen in α-pinene and β-pinene molecules.

Effect of methyl substituents on the preferred conformations of Bis(pentadienyl) open metallocenes

Density functional theory (DFT) methods indicated that the preferred geometries, spin states, and energetics of unsubstituted bis(pentadienyl)metal open sandwich complexes (C5H7)2M of the first row transition metals (M = Ti to Ni) are similar to those of the corresponding substituted and more stable (2,4-Me2C5H5)2M open sandwich complexes with 2,4-dimethylpentadienyl ligands. Structures with two fully bonded pentahapto η5-C5H7 ligands are energetically preferred for iron and for the transition metals to the left of iron in the Periodic Table. However, for the electron-rich first-row transition metals cobalt and nickel, structures with at least one trihapto η3-C5H7 ligand are preferred in order to prevent the electron configuration of the central metal atom from exceeding the favored 18-electrons. For the manganese systems (C5H7)2Mn and (2,4-Me2C5H5)2Mn the presence of the two methyl substituents is found to have little effect on the complicated potential energy surface with low-energy structures in the doublet, quartet, and sextet spin states.

Recent advances in chemistry of high-spin nitrenes

Experimental and theoretical studies on aromatic nitrenes bearing from three to six unpaired electrons and having quartet, quintet, sextet or septet ground spin states, published in the last 15 years are analyzed. A comparative analysis of the magnetic properties of high-spin nitrenes and all other known high-spin organic molecules is performed. Promising areas of practical application of high-spin nitrenes as molecular magnets and as qubits and qudits for quantum computations are discussed.The bibliography includes 214 references.

Insight into structural aspects and study of reaction kinetics of model [oxo(salen)iron(IV)] complexes with dipeptides

Iron(III)-salen complexes (salen = N,N’-bis(salicylidene)ethylenediaminato) react with H2O2 in aqueous CH3CN medium to form short lived intermediate [oxo(salen)iron(IV)] radical cation as an active oxidant. The present study devotes to establish the nature and reactivity of this active oxidant by spectral (UV–vis and Mössbauer), electrochemical (Cyclic voltammetric) and density functional theory (DFT) method. Mössbauer spectral study gives a clue to the formation of [oxo(salen)iron(IV)] radical cation with doublet (S = 2) spin multiplicity as an intermediate. Geometry optimization of oxo-iron species using DFT method, Mulliken charges and spin densities uphold that the doublet (S = 2) state is more stable and less in energy than the quartet (S = 4) and sextet (S = 6) spin states. The calculated average FeO bond distance for all the [oxo(salen)iron(IV)] complexes is 1.63 Å which is in good agreement with X-ray crystallography value of 1.65 Å. The CV study shows a clear oxidation wave at 1.18 (±0.02) V with increase in the oxidation peak current for FeIII/FeIV redox couple. Kinetics of oxygenation of four dipeptides (eg. Met-Gly, Met-Ala, Met-Leu, Met-Ser) with [oxo(salen)iron(IV)] radical cation into the corresponding sulfone follow Michaelis-Menten kinetics. The reaction rate is sensitive to the nature of the substituent present in the phenolic part of salen ligand and side chain present in the peptides. To account for spectral, kinetic and DFT results a suitable mechanism has been proposed.

Anticancer evaluation of a manganese complex on HeLa and MCF-7 cancer cells: design, deterministic solvothermal synthesis approach, Hirshfeld analysis, DNA binding, intracellular reactive oxygen species production, electrochemical characterization and density functional theory

Herein, a deterministic solvothermal strategy was employed to synthesize an efficient anticancer agent ‘cis-dichlorobis(1,10-phenanthroline)manganese(II)’ (Mn(phen)2Cl2). A single-crystal X-ray diffraction analysis revealed that Mn(phen)2Cl2 crystallizes in a triclinic system with the space group P-1. Cyclic voltammetric studies of Mn(phen)2Cl2 indicated that the electrode process occurs only due to complex formation and has a diffusion-controlled mechanism. Density functional theory estimations showed that the Mn(phen)2Cl2 is quite stable and exists in sextet spin state (five unpaired electrons) as the most stable form and hence, Mn(phen)2Cl2 is a high spin complex. Mn(phen)2Cl2 demonstrated significant anticancer potential against HeLa and MCF-7 cancer cells and less toxic behaviour towards normal BHK-21 cells. Fluorescence imaging confirmed that the production of reactive oxygen species (ROS) in HeLa cells by Mn(phen)2Cl2 induces oxidized fluorescence of dichlorofluorescein which emitted fluorescence at 530 nm after excitation at 488 nm. The microscopic investigation of apoptotic effect of Mn(phen)2Cl2 using propidium iodide and 4′,6-diamidino-2-phenylindole staining indicated that nuclear condensation, cell detachment and shrinkage occur after treatment with IC50 values of Mn(phen)2Cl2. Furthermore, an assessment of caspase-9 and caspase-3 activity after exposure to Mn(phen)2Cl2 in HeLa cells indicated that at IC50 values of Mn(phen)2Cl2, 1.5 fold and 4.8 fold increase in caspase-9 and caspase-3 activity, respectively, occurs. The measurement of mitochondrial membrane potential of a cationic dye (JC-1) showed a decrease in mitochondrial membrane potential in both HeLa and MCF-7 cells depicting that compound might have adopted intrinsic pathway of apoptosis. Ability of Mn(phen)2Cl2 to interact with HS-DNA demonstrates hyperchromicity with slight blue shift from 269 nm to 265 nm showing a non-covalent interaction with Gibbs free energy of ΔG = −14.62 kJ/mol. Communicated by Ramaswamy H. Sarma

Trapping Iron(III)-Oxo Species at the Boundary of the "Oxo Wall": Insights into the Nature of the Fe(III)-O Bond.

Terminal non-heme iron(IV)-oxo compounds are among the most powerful and best studied oxidants of strong C-H bonds. In contrast to the increasing number of such complexes (>80 thus far), corresponding one-electron-reduced derivatives are much rarer and presumably less stable, and only two iron(III)-oxo complexes have been characterized to date, both of which are stabilized by hydrogen-bonding interactions. Herein we have employed gas-phase techniques to generate and identify a series of terminal iron(III)-oxo complexes, all without built-in hydrogen bonding. Some of these complexes exhibit ∼70 cm-1 decrease in ν(Fe-O) frequencies expected for a half-order decrease in bond order upon one-electron reduction to an S = 5/2 center, while others have ν(Fe-O) frequencies essentially unchanged from those of their parent iron(IV)-oxo complexes. The latter result suggests that the added electron does not occupy a d orbital with Fe═O antibonding character, requiring an S = 3/2 spin assignment for the nascent FeIII-O- species. In the latter cases, water is found to hydrogen bond to the FeIII-O- unit, resulting in a change from quartet to sextet spin state. Reactivity studies also demonstrate the extraordinary basicity of these iron(III)-oxo complexes. Our observations show that metal-oxo species at the boundary of the "Oxo Wall" are accessible, and the data provide a lead to detect iron(III)-oxo intermediates in biological and biomimetic reactions.

Synthesis, X-ray crystal structure and spin polarized DFT study of high spin Mn based metal-organic framework

Theoretical modeling of the geometries of metal-organic frameworks is quite challenging. In order to compare the geometry obtained through density functional theory (DFT) calculations with the one obtained experimentally, a hydrothermal reaction of the potassium salt of 1,1-cyclopentane diacetic acid (L) with MnCl2·2H2O in the presence of 4,4′-bipyridine (bpy) was carried out which formulated a two dimensional metal-organic framework [Mn2(L)2(bpy)2(H2O)2]n∙6H2O. Single crystal X-ray diffraction analysis reveals that the compound crystallized in the centrosymmetric monoclinic space group P 2/n. The presence of solvate water molecules of crystallization offer hydrogen bond formation and result the connection of 2-D sheets into 3-D hydrogen bonded metal-organic framework. The manganese atom can have a maximum of sextet spin state (five unpaired electrons). Single point energies were calculated at M05-2X/6-31G (d,p) for different spin states (up to 11 et) of the high energy framework and it was elucidated that the 11et spin stat is the lowest energy spin state.

Low-Spin Fe(III) Macrocyclic Complexes of Imidazole-Appended 1,4,7-Triazacyclononane as Paramagnetic Probes.

Two macrocyclic complexes of 1,4,7-triazacyclononane (TACN), one with N-methyl imidazole pendants, [Fe(Mim)]3+, and one with unsubstituted NH imidazole pendants, [Fe(Tim)]3+, were prepared with a view toward biomedical imaging applications. These low-spin Fe3+ complexes produce moderately paramagnetically shifted and relatively sharp 1H NMR resonances for paraSHIFT and paraCEST applications. The [Fe(Tim)]3+ complex undergoes pH-dependent changes in NMR spectra in solution that are consistent with the consecutive deprotonation of all three imidazole pendant groups at high pH values. N-Methylation of the imidazole pendants in [Fe(Mim)]3+ produces a complex that dissociates more readily at high pH in comparison to [Fe(Tim)]3+, which contains ionizable donor groups. Cyclic voltammetry studies show that the redox potential of [Fe(Mim)]3+ is invariant with pH ( E1/2 = 328 ± 3 mV vs NHE) between pH 3.2 and 8.4, unlike the Fe(III) complex of Tim which shows a 590 mV change in redox potential over the pH range of 3.3-12.8. Magnetic susceptibility studies in solution give magnetic moments of 0.91-1.3 cm3 K mol-1 (μeff value = 2.7-3.2) for both complexes. Solid-state measurements show that the susceptibility is consistent with a S = 1/2 state over the temperature range of 0 to 300 K, with no crossover to a high-spin state under these conditions. The crystal structure of [Fe(Mim)](OTf)3 shows a six-coordinate all-nitrogen bound Fe(III) in a distorted octahedral environment. Relativistic ab initio wave function and density functional theory (DFT) calculations on [Fe(Mim)]3+, some with spin orbit coupling, were used to predict the ground spin state. Relative energies of the doublet, quartet, and sextet spin states were consistent with the doublet S = 1/2 state being the lowest in energy and suggested that excited states with higher spin multiplicities are not thermally accessible. Calculations were consistent with the magnetic susceptibility determined in the solid state.

Spin‐State‐Controlled Photodissociation of Iron(III) Azide to an Iron(V) Nitride Complex

AbstractThe generation of iron(V) nitride complexes, which are targets of biomimetic chemistry, is reported. Temperature‐dependent ion spectroscopy shows that this reaction is governed by the spin‐state population of their iron(III) azide precursors and can be tuned by temperature. The complex [(MePy2TACN)Fe(N3)]2+ (MePy2TACN=N‐methyl‐N,N‐bis(2‐picolyl)‐1,4,7‐triazacyclononane) exists as a mixture of sextet and doublet spin states at 300 K, whereas only the doublet state is populated at 3 K. Photofragmentation of the sextet state complex leads to the reduction of the iron center. The doublet state complex photodissociates to the desired iron(V) nitride complex. To generalize these findings, we show results for complexes with cyclam‐based ligands.

Spin-State-Controlled Photodissociation of Iron(III) Azide to an Iron(V) Nitride Complex.

The generation of iron(V) nitride complexes, which are targets of biomimetic chemistry, is reported. Temperature-dependent ion spectroscopy shows that this reaction is governed by the spin-state population of their iron(III) azide precursors and can be tuned by temperature. The complex [(MePy2 TACN)Fe(N3 )]2+ (MePy2 TACN=N-methyl-N,N-bis(2-picolyl)-1,4,7-triazacyclononane) exists as a mixture of sextet and doublet spin states at 300 K, whereas only the doublet state is populated at 3 K. Photofragmentation of the sextet state complex leads to the reduction of the iron center. The doublet state complex photodissociates to the desired iron(V) nitride complex. To generalize these findings, we show results for complexes with cyclam-based ligands.

Cryo IR Spectroscopy of [Hemin]+ Complexes in Isolation.

We present cryo IR spectra of isolated [Hemin]+ adducts with CO, N2, and O2 ([Hemin(CO)1]+, [Hemin(CO)2]+, [Hemin(14N2)]+, [Hemin(15N2)]+, and [Hemin(O2)]+). Well resolved bands allow for the elucidation of structure and spin multiplicity in conjunction with density functional (DFT) calculations. There is a quartet spin state for the N2 and CO adducts and a sextet spin state for the O2 adduct, where the O2 retains its triplet state. The double CO adsorption induces significant changes in the vibrational patterns of the IR spectra, which we take as strong evidence for a spin quenching into a doublet. Our study characterizes [Hemin]+, which is the Fe3+ oxidation product of heme that is of ubiquitous presence in hemeproteins.

Tensor network states with three-site correlators

We present a detailed analysis of various tensor network parameterizations within the complete graph tensor network states (CGTNS) approach. We extend our 2-site CGTNS scheme by introducing 3-site correlators. For this we devise three different strategies. The first relies solely on 3-site correlators and the second on 3-site correlators added on top of the 2-site correlator ansatz. To avoid an inflation of the variational space introduced by higher-order correlators, we limit the number of higher-order correlators to the most significant ones in the third strategy. Approaches for the selection of these most significant correlators are discussed. The sextet and doublet spin states of the spin-crossover complex manganocene serve as a numerical test case. In general, the CGTNS scheme achieves a remarkable accuracy for a significantly reduced size of the variational space. The advantages, drawbacks, and limitations of all CGTNS parameterizations investigated are rigorously discussed.

Spin-Controlled Conductivity in a Thiophene-Functionalized Iron-Bis(dicarbollide)

The relationship between spin state and conductivity is studied for a thiophene-functionalized iron(III)-bis(dicarbollide) with one or two thiophenes at each end of the cage. Iron has a high ground state spin that can be adjusted by external electromagnetic fields to produce different magnetic states. The hypothesis explored here is that changes in the spin state of these Fe-containing molecules can lead to significant changes in molecular conductivity. Two examples of the possible application of such spin-dependent conductivity are its use as a molecular switch, the basic building block in digital logic, or as a memory bit. The molecules were first optimized using the Becke-3 Lee–Yang–Parr functional (B3LYP) with the 6-31G(d) basis set. A relaxed molecular geometry at each spin state was then placed between gold electrodes to conduct spin-polarized electron transport calculations with the density functional theory/non-equilibrium Green’s functions formalism. The revised Perdew–Burke–Ernzerhf solids exchange–correlation functional (PBES) with double zeta polarized basis set was used. The result of these calculations show that the conductivity increases with the spin state. The cage structure is shown to exhibit fully delocalized molecular orbitals (MOs) appropriate for high conductivity and thus, in this system, the conductivity depends on the position of the MOs relative to the Fermi level. Minority spins are responsible for the conductivity of the doublet spin state while majority spins dominate for the quartet and sextet spin states as they are found closer to the Fermi level when they are occupied. Energy calculations predict a difference in energy between the more and the less conductive spin states (sextet and doublet respectively) that is 15–20 times greater than the thermal energy, which would imply stability at room temperature; however, the energy difference is sufficiently small that transitions between spin states can be induced.

Manganese-centered ten-vertex germanium clusters: the strong field Ge10 ligand encapsulating a transition metal

The experimental realization of pentagonal prismatic structures for M@ (M = Co, Fe) containing interstitial transition metal atoms makes of interest the chemistry of corresponding manganese derivatives Mn@. The neutral Mn@Ge10 may be regarded as a complex of a polyhedral ligand with an interstitial Mn in the +2 oxidation state. However, the lowest energy Mn@Ge10 structure with the expected sextet spin state for high-spin d5 Mn(II) lies ~23 kcal mol−1 in energy above the lowest energy isomer thereby suggesting that such germanium polyhedra function as strong field ligands for encapsulated transition metals. The lowest energy structures for the Mn@ anions (z = −1 to −5) are all centered pentagonal prisms. Higher energy Mn@ structures have outer Ge10 polyhedra based on the tetracapped trigonal prism similar to the lowest energy Co@ structure and on the bicapped square antiprism similar to the B10 deltahedron. Other Mn@ structures have outer Ge10 polyhedra with four or five quadrilateral faces as well as six or eight triangular faces, respectively. Bioctahedral (Ge5)2Mn5− structures were also found for the pentaanion with a manganese vertex common to two MnGe5 octahedra. The cationic species Mn@ was found to have a more complicated potential surface than the anions. Tetracapped trigonal prismatic and bicapped square antiprismatic structures as well as a variety of more open structures were found for Mn@.

Structure and bonding analysis of intermediate model heme-imidazole and heme-thiolate enzymes complexed with formate, acetate and nitrate: A theoretical study

Structure and bonding analysis of the FeO bonds in the model heme-imidazole and heme-thiolate complexes [(por)Fe(Im)(R)] (R=HC(O)O−, 1FeIm, R=H3CC(O)O−, 2FeIm, R=NO3−, 3FeIm) and [(por)Fe(SMe))(R)]− (R=HC(O)O−, 4FeSMe, R=H3CC(O)O−, 5FeSMe, R=NO3−, 6FeSMe) were investigated at the DFT/TZP level of theory using density functionals BP86, PW91, PBE, TPSS and B3LYP. The FeO bond distances at BP86/TZP in the complexes [(por)Fe(Im)(R)] (1.858Å in 1FeIm, 1.868Å in 2FeIm and 1.919Å in 3FeIm) and [(por)Fe(SMe)(R)]− (1.955Å in 4FeSMe, 1.981Å in 5FeSMe and 1.991Å in 6FeSMe) are longer than those expected for a FeO single bond estimated on the basis of covalent radii predictions (FeO=1.79Å). The FeO bond distances in [(por)Fe(Im)(R)] 1FeIm–3FeIm are shorter than those in [(por)Fe(SMe)(R)]−4FeSMe–6FeSMe. The thiolate is more trans-directing ligand than the imidazole ligand. The results of optimized geometries, NPA charges, Wiberg bond indices, NHO analysis and BDEs clearly indicate that the formate, acetate and nitrate ligands bind more weakly in heme-thiolate complexes than in heme-imidazole complexes. The reaction intermediate of chloroperoxidase enzyme would be more reactive with organic substrates than the myeloperoxidase (MPO) enzyme. The quartet and the sextet spin states are less stable than the doublet spin state. The optimized bond distances are shortest for doublet spin state.

Electronic properties of the low-lying spin states of dimethylnitrosamine coordinated to Fe(III) heme models: An ab initio study

The unusual O-coordination mode of nitrosamines to Fe(III) heme models has been observed in the bis(dimethylnitrosamine)(meso-tetraphenylporphyrinate)iron(III) cation. For the first time, this latter as well as the simpler bis(dimethylnitrosamine)(porphinate)iron(III) heme model cations have been studied through ab initio methods. The sextet, quartet, and doublet spin states of both cations have been studied through single-point calculations based on the experimental (X-ray) geometry. Their energies, charges, and spin densities have been analyzed. The obtained results (at the UHF/cc-pVDZ and ROHF/cc-pVDZ levels) indicate that the peripheral benzene rings are of secondary importance for the coordination of dimethylnitrosamine to the Fe(III) porphyrin core. The obtained energy ordering is sextet < quartet < doublet, at all computational levels. The UHF, ROHF, and UMP2 results indicate an excess of alpha spin density around the Fe atom, a low covalency for the FeO bond and a substantial charge transfer to the Fe atom. Our best estimates [obtained at ROMP2 level with the mixed cc-pVDZ/cc-pVTZ-DK(Fe) basis set] for the energy differences (in eV) between the three spin states considered are 0.929 for the sextet-quartet gap and 0.812 for the quartet-doublet gap, which indicate that the spin crossover (at room temperature) is very unlikely. These results represent the substantial decrease in the uncorrelated values. The implications of spin contaminations at the UHF and UMP2 levels for subsequent geometry optimizations to be performed in the smaller cation have also been discussed. © 2013 Wiley Periodicals, Inc.

Gaseous Vanadium Molybdate and Tungstates: Thermodynamic Properties and Structures

The stability of gaseous vanadium molybdate and vanadium tungstates was confirmed by high-temperature mass spectrometry. A number of gas-phase reactions involving vanadium-containing salts were studied. On the basis of equilibrium constants, the standard formation enthalpies of gaseous VMoO(4) (-676 ± 27 kJ/mol), VWO(3) (-331 ± 29 kJ/mol), and VWO(4) (-706 ± 23 kJ/mol) at 298 K were determined. A theoretical study of these salts revealed the structure with bidentate binding of the vanadium cation to the anion part to be the lowest-lying isomer, with a quartet spin state for VMoO(4) and VWO(4) molecules as well as a sextet spin state for the VWO(3) molecule. On the basis of critical analysis of the literature data concerning standard formation enthalpies of gaseous VO and VO(2), we adopted new values of Δ(f)H°(298) = 135 ± 10 kJ/mol for VO(g) and -185 ± 15.0 kJ/mol for VO(2)(g). Overall, the results obtained allowed us to estimate the standard formation enthalpy of VMoO(3) to be -318 kJ/mol with an accuracy near 40 kJ/mol.

Investigation of spin-flip reactions of Nb + CH3CN by relativistic density functional theory

In order to explore the details of the reaction mechanisms of Nb atoms with acetonitrile molecules, the sextet, quartet, and doublet spin state potential energy surfaces have been investigated. Density functional theory (DFT) with the relativistic zero-order regular approximation at the PW91/TZ2P level has been applied. The complicated minimum energy reaction path involves four transition states (TS), stationary states (1) to (5) and two intersystem crossings from spin sextets to quartets to doublets (indicated by ⇒): (6)Nb + NCCH3→(6)Nb η(1)-NCCH3 ((6)1) →(6)TS1/2⇒(4)Nb η(2)-(NC)CH3 ((4)2) →(4)TS2/3→(4)NbH η(3)-(NCCH2) ((4)3) →(4)TS3/4→ CNNbCH3 ((4)4) ⇒(2)TS4/5→ CN(NbH)CH2 ((2)5). The minimum energy crossing points were determined with the help of the DFT fractional-occupation-number approach. The first spin inversion leads from the sextet to an energetically low intermediate quartet ((4)2) with final insertion of Nb into the C-C bond. The second one from the quartet to the doublet state facilitates the activation of a C-H bond, lowering the rearrangement-barrier by 44 kJ mol(-1). The overall reaction is calculated to be exothermic by about 170-180 kJ mol(-1). All intermediate and product species were frequency and NBO analyzed. The species can be rationalized with the help of Lewis type formulas.

Regioselectivity of aliphatic versus aromatic hydroxylation by a nonheme iron(ii)-superoxo complex

Many enzymes in nature utilize molecular oxygen on an iron center for the catalysis of substrate hydroxylation. In recent years, great progress has been made in understanding the function and properties of iron(IV)-oxo complexes; however, little is known about the reactivity of iron(II)-superoxo intermediates in substrate activation. It has been proposed recently that iron(II)-superoxo intermediates take part as hydrogen abstraction species in the catalytic cycles of nonheme iron enzymes. To gain insight into oxygen atom transfer reactions by the nonheme iron(II)-superoxo species, we performed a density functional theory study on the aliphatic and aromatic hydroxylation reactions using a biomimetic model complex. The calculations show that nonheme iron(II)-superoxo complexes can be considered as effective oxidants in hydrogen atom abstraction reactions, for which we find a low barrier of 14.7 kcal mol(-1) on the sextet spin state surface. On the other hand, electrophilic reactions, such as aromatic hydroxylation, encounter much higher (>20 kcal mol(-1)) barrier heights and therefore are unlikely to proceed. A thermodynamic analysis puts our barrier heights into a larger context of previous studies using nonheme iron(IV)-oxo oxidants and predicts the activity of enzymatic iron(II)-superoxo intermediates.