Quantum mechanical models of the resting state of the vanadium-dependent haloperoxidase

Density functional theory has been used to investigate structural and electronic properties of complexes related to the resting form of the active site of vanadium haloperoxidase as a function of environment and protonation state. Results obtained by studying models of varying size and complexity highlight the influence of environment and protonation state on the structure and stability of the metal cofactor. The study shows that, in the trigonal bipyramidal active site, where one axial position is occupied by a key histidine, the trans position cannot contain a terminal oxo group. Further, a highly negatively charged vanadate unit is not stable. Protonation of at least one equatorial oxo ligand appears necessary to stabilize the metal cofactor. The study also indicates that, while at rest within the protein, the vanadate unit is most likely an anion with an axial hydroxide and an equatorial plane containing two oxos and a hydroxide. For the neutral, protonated state of the vanadate unit, there were two minima found. The first structure is characterized by an axial water with two oxo and one hydroxo group in the equatorial plane. The second structure contains an axial hydroxo group and an equatorial plane composed of one oxo and two hydroxo oxygen atoms. These two species are not significantly different in energy, indicating that either form may be important during the catalytic cycle. These data support the initial crystallographic assignment of an axially bound hydroxide, but an axial water is also a possibility. This study also shows that the protonation state of the vanadate ion is most likely greater than previously proposed.     

Reactivity of peroxo forms of the vanadium haloperoxidase cofactor. A DFT investigation

Density functional theory has been used to investigate structural, electronic and reactivity properties of complexes related to the peroxo forms of vanadium haloperoxidases (VHPO). In particular, the reactivity of the cofactor as a function of protonation state and environment, which are two factors thought to be crucial in modulating the activity of the enzyme, has been examined. In full agreement with experimental data, results highlight the role of protonation in the activation of the peroxo-vanadium complexes and show that the oxo-transfer step involves the unprotonated axial peroxo oxygen atom, which is easily accessible to substrates in the peroxo form of the enzyme. The role of Lys353, which in the X-ray structure of the peroxide-bound form of vanadium chloroperoxidase is hydrogen bonded to the equatorial oxygen atom of the peroxo group, has been also explored. It is concluded that Lys353 can play a role similar to a H+ in the activation of the peroxo form of the cofactor.     

The chemistry of peroxovanadium species in aqueous solutions. Structure and reactivity of a neutral diperoxovanadium complex as provided by V-NMR data, ab initio calculations and kinetic results

The addition of hydrogen peroxide to vanadium (V) precursors in aqueous acidic solutions leads to the formation of a cationic monoperoxospecies [VO(O₂)]⁺ and an anionic diperoxocomplex [VO(O₂)₂]⁻, depending on the pH and on the excess of H₂O₂. The latter may undergo protonation to form the neutral complex [HVO(O₂)₂]. ⁵¹V-NMR data and ab initio calculations suggest that the neutral complex is formed via protonation of a peroxide oxygen and that in such a species, as well as in the other two peroxovanadium derivatives, the usual η² arrangement of the peroxo groups is maintained. The comparison of reactivity data of the three complexes in the self-decomposition reaction and in the oxidation of uracil, indicates that the neutral diperoxocomplex exhibits an oxidizing power considerably larger than that of the other two peroxovanadium species.     

Insight into the catalytic mechanism of vanadium haloperoxidases. DFT investigation of vanadium cofactor reactivity

Density functional theory (DFT) has been used to investigate the catalytic properties of the isolated vanadium cofactor found in vanadium haloperoxidases, with a particular emphasis on the steps going from the resting form of the cofactor to the peroxo complex. Computation of transition states, intermediate species, and UV-vis spectra, as well as comparison of reaction energies, demonstrated the important role of protonation in cofactor activation. This illustrates that the resting form of the vanadium cofactor reacts with hydrogen peroxide according to a mechanism that implies formation of an aqua complex, release of the apical water molecule according to a dissociative pathway, and binding of hydrogen peroxide to vanadium. This process leads to a side-on peroxo species corresponding to the peroxo form observed in the enzyme. In addition, it appears that an acid-base catalysts strongly accelerates the conversion to the side-on peroxo form. The comparison of computed and experimental UV-vis spectra corroborated the proposed reaction pathway and allowed us to explain the effects of the vanadium ligands on the electronic properties of the cofactor.     

Aquaperoxovanadium(V) complexes: Quantum-chemical study

The addition of a water molecule to mono-, di-, and triperoxovanadium(V) complexes has been studied at the density functional theory (B3LYP/6-31G**) and Møller-Plesset perturbation theory (MP2/6-31G**) levels. It has been demonstrated that the H₂O…V donor-acceptor interaction cannot compete with hydrogen bonds and becomes weaker with an increase in the number of peroxo groups in the complex. In the most stable isomers of aquaperoxo complexes, water is mainly held by intermediate hydrogen bonds. The energy of addition of a water molecule to peroxovanadate is lower than or close to the heat of evaporation of water; i.e., the formation of stable aquaperoxovanadium complexes in aqueous solutions is improbable. This conclusion is consistent with the mass spectra of aqueous solutions of peroxovanadates, which show that the concentration of water-free peroxo complexes considerably exceeds the concentration of complexes with a coordinated water molecule. The coordination of the water molecule through the V…OH₂ donor-acceptor interaction is prevented by the cis effect of the peroxo group, which has the HOMO orbital of symmetry suitable for interaction with the LUMO orbital of the VO group.     

51V NMR chemical shifts calculated from QM/MM models of vanadium chloroperoxidase

(51)V NMR chemical shifts calculated from QM/MM-optimized (QM=quantum mechanical; MM=molecular mechanical) models of vanadium-dependent chloroperoxidase (VCPO) are presented. An extensive number of protonation states for the vanadium cofactor (active site of the protein) and a number of probable positional isomers for each of the protonation states are considered. The size of the QM region is increased incrementally to observe the convergence behavior of the (51)V NMR chemical shifts. A total of 40 models are assessed by comparison to experimental solid-state (51)V NMR results recently reported in the literature. Isotropic chemical shifts are found to be a poor indicator of the protonation state; however, anisotropic chemical shifts and the nuclear quadrupole tensors appear to be sensitive to changes in the proton environment of the vanadium nuclei. This detailed investigation of the (51)V NMR chemical shifts computed from QM/MM models provides further evidence that the ground state is either a triply protonated (one axial water and one equatorial hydroxyl group) or a doubly protonated vanadate moiety in VCPO. Particular attention is given to the electrostatic and geometric effects of the protein environment. This is the first study to compute anisotropic NMR chemical shifts from QM/MM models of an active metalloprotein for direct comparison with solid-state MAS NMR data. This theoretical approach enhances the potential use of experimental solid-state NMR spectroscopy for the structural determination of metalloproteins.     

Vicarious nucleophilic substitution of hydrogen versus vinylic substitution of halogen in the reactions of carbanions of halomethyl aryl sulfones with dialkyl halofumarates and halomaleates

Reaction of halomethyl aryl sulfone carbanions with dialkyl halofumarates and halomaleates results in nucleophilic substitution of hydrogen and/or of the halogen. The reaction with halofumarates proceeds via addition of the carbanions to the vinylic carbon atom connected with hydrogen, followed by base promoted β-elimination of hydrogen halide in which the halogen originates from the carbanion moiety or from the alkene. In the case of halomaleates the reaction proceeds via an elimination-addition sequence.     

A persistent alkylaluminum peroxide: surprising stability of a molecule with strong reducing and oxidizing functions in close proximity

The reaction of the beta-diketiminato coordinated aluminum dihydride, [{HC[C(Me)N-C(6)H(5)](2)}AlH(2)] (1) with bis(trimethylsilyl)methyllithium afforded the monoalkylaluminum derivative [{HC[C(Me)N-C(6)H(5)](2)}Al(H)-CH(SiMe(3))(2)] (2) by the precipitation of lithium hydride. Interestingly, treatment of 2 with tert-butyl hydrogenperoxide did not result in the formation of the simple oxidation product containing a hydroxo or alkoxo group, instead, elemental hydrogen was released and the hydrido ligand attached to aluminum was replaced by an intact tert- butylperoxo group. The Al-C bond, which normally is extremely sensitive towards an attack of oxygen, was not affected. Hence, the product exhibits quite conflicting chemical properties in a close proximity: a strongly reducing Al-C bond beside an oxidizing peroxo group.     

Metal nature effect on catalytic reactions in furfural-H2O2-H2O-group V or VI d-metal salt systems in acid media

Homogeneous catalytic reactions of furfural oxidation by hydrogen peroxide in an aqueous medium in the presence of catalytic amounts of a vanadium, niobium, molybdenum, or chromium salt have been studied to compare them with the acid-autocatalytic reaction. The formation of peroxo complexes of the corresponding metals has been established. The interaction of these peroxo complexes with the carbonyl group of furfural affords organic metal-containing peroxides. The subsequent transformations of these peroxides in the presence of the indicated catalysts lead to different dominant final products. This is explained by different mechanisms of the oxidation of the key intermediates, namely, 2-formyloxy- and 2-hydroxyfurans. In the presence of the vanadium and molybdenum salts, the catalytic role of the resuting carboxylic acids is insignificant, as distinct from what is observed in the acid-autocatalyzed reaction.

     

The role of peroxo complexes in the catalytic decomposition of H2O2 in the presence of Cu(II) hydroxides

The catalytic decomposition of hydrogen peroxide is studied in the presence of colloidal and silicagel-supported Cu(OH)₂. Copper peroxo complexes with different activities were identified. The reaction is molecular without radical formation. The mechanisms of H₂O₂ decomposition are discussed.     

A Product Formed from Glycylglycine in the Presence of Vanadate and Hydrogen Peroxide: The (Glycylde-N-hydroglycinato-kappa(3)N(2),N(N)(),O(1))oxoperoxovanadate(V) Anion

A crystalline glycylglycine complex of monoperoxovanadate has been obtained and its X-ray structure determined. The coordination is pentagonal bipyramidal with the peroxo group and a tridentate glycylglycine occupying the equatorial positions. The axial positions of the anion are occupied by the oxo ligand and by one oxygen of the peroxo group of the adjacent anion. The latter interaction establishes the seventh bond and produces a dimeric structure in the crystalline material. NMR studies of its dissolution in water combined with previously reported results from equilibrium measurements show that the dimer dissociates in water to the monomeric precursor. It is proposed that this monomer corresponds to the complex responsible for the inhibition of the vanadium-catalyzed decomposition of hydrogen peroxide by glycylglycine. Crystal structure of [NEt(4)][VO(O(2))(GlyGly)].1.58H(2)O: monoclinic, space group P2(1); Z = 4; a = 10.618(2) ?; b = 14.803(2) ?; c = 11.809(2) ?; beta = 101.37(2) degrees; V = 1819.7 ?(3); T = 198 K; R(F)() = 0.029 for 2664 data (I(o) >/= 2.5sigma(I(o))) and 431 variables.     

Elucidating the protonation site of vanadium peroxide complexes and the implications for biomimetic catalysis

Coordination complexes of vanadium(5+) played a key role in understanding the structure and mechanism of vanadium-dependent haloperoxidases, particularly the effects of protonation on peroxide coordination to dioxovanadium(5+) species, and in the activation of the peroxo-oxovanadium(5+) complex for substrate oxidation. There has been no spectroscopic evidence that could test the presence of a hydroxo intermediate in a catalytically active oxovanadium(5+) complex. Herein we report the use of the pre-edge transition in X-ray absorption spectroscopy as a spectroscopic signature for V=O bonding. Displacement of oxo donors with hydrogen peroxide or chloride donors dramatically decreases the pre-edge intensity, confirming that the source of the intense pre-edge feature is closely related to the -bonding associated with the V=O. Protonation of a catalytically active tripodal amine oxovanadium(5+) complex has no affect on the pre-edge intensity and, therefore, rules out the possibility of a hydroxo intermediate in the catalytic cycle.     

Remarkable Anion‐Dependent Spin‐State Switching in Diiron(III) μ‐Hydroxo Bisporphyrins: What Role Do Counterions Play?

Addition of 2,4,6‐trinitrophenol (HTNP) to an ethene‐bridged diiron(III) μ‐oxo bisporphyrin ( 1 ) in CH₂Cl₂ initially leads to the formation of diiron(III) μ‐hydroxo bisporphyrin ( 2? TNP) with a phenolate counterion that, after further addition of HTNP or dissolution in a nonpolar solvent, converts to a diiron(III) complex with axial phenoxide coordination ( 3? (TNP)₂). The progress of the reaction from μ‐oxo to μ‐hydroxo to axially ligated complex has been monitored in solution by using ¹H NMR spectroscopy because their signals appear in three different and distinct spectral regions. The X‐ray structure of 2? TNP revealed that the nearly planar TNP counterion fits perfectly within the bisporphyrin cavity to form a strong hydrogen bond with the μ‐hydroxo group, which thus stabilizes the two equivalent iron centers. In contrast, such counterions as I₅, I₃, BF₄, SbF₆, and PF₆ are found to be tightly associated with one of the porphyrin rings and, therefore, stabilize two different spin states of iron in one molecule. A spectroscopic investigation of 2? TNP has revealed the presence of two equivalent iron centers with a high‐spin state (S=5/2) in the solid state that converts to intermediate spin (S=3/2) in solution. An extensive computational study by using a range of DFT methods was performed on 2? TNP and 2 ⁺, and clearly supports the experimentally observed spin flip triggered by hydrogen‐bonding interactions. The counterion is shown to perturb the spin‐state ordering through, for example, hydrogen‐bonding interactions, switched positions between counterion and axial ligand, ion‐pair interactions, and charge polarization. The present investigation thus provides a clear rationalization of the unusual counterion‐specific spin states observed in the μ‐hydroxo bisporphyrins that have so far remained the most outstanding issue.     

Advantages of organic halogen bonding for halide recognition

The synthesis of a bidentate halogen bonding receptor and a nearly isostructural hydrogen bonding analogue is described. Crystal structures reveal the interactions of each receptor with anions in the solid state, while NMR titrations elucidate bidentate binding and association constants in solution. Of the two, the halogen bonding receptor demonstrates stronger, water resistant halide binding in competitive solvents.     

Effect of protonation on the conformation of cinchonidine

The protonation of cinchona alkaloids in solution leads to the severe restriction of their internal rotational degrees of freedom and to the locking of the molecule around a specific conformation held in place by a bridging counterion of the acid used for protonation. For HF, direct interactions were detected by NMR between the fluorine anion and not only with the acidic hydroxo group but also with non-acidic hydrogen atoms in the quinoline ring.     

New insights into the reaction of t-butylhydroperoxide with dichloro- and dimethyl(dioxo)molybdenum(VI)

Lewis-base adducts of dichlorodioxomolybdenum(VI) and dimethyldioxomolybdenum(VI) react in an equilibrium reaction with excess t-butylhydroperoxide (TBHP) under the formation of a seven-coordinated molybdenum(VI) complexes displaying a η¹-alkylperoxo-ligand. HCl/CH₄ elimination or the protonation of the Lewis-base ligand is not observed, the TBHP hydrogen atom is instead transferred to one of the terminal oxo ligands under the formation of a molybdenum bound OH moiety. The peroxo species is assumed to be the active catalyst in olefin epoxidation.     

卤代苯与水分子间作用的从头算

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A Halogen‐Bonding Bis‐triazolium Rotaxane for Halide‐Selective Anion Recognition

A systematic study on the anion‐binding properties of acyclic halogen‐ and hydrogen‐bonding bis‐triazolium carbazole receptors is described. The halide‐binding potency of halogen‐bonding bis‐iodotriazolium carbazole receptors was found to be far superior to their hydrogen‐bonding bis‐triazolium‐based analogues. This led to the synthesis of a mixed halogen‐ and hydrogen‐bonding rotaxane host containing a bis‐iodotriazolium carbazole axle component. The rotaxane’s anion recognition properties, determined by ¹H NMR titration experiments in a competitive aqueous solvent mixture, demonstrated the preorganised halogen‐bonding interlocked host cavity to be halide‐selective, with a strong binding affinity for bromide.