Zr-monosubstituted Lindqvist-type polyoxometalates (Zr-POMs), (Bu 4 N) 2 [W 5 O 18 Zr(H 2 O) 3 ] (1) and (Bu 4 N) 6 [{W 5 O 18 Zr(μ-OH)} 2 ] (2), have been employed as molecular models to unravel the mechanism of hydrogen peroxide activation over Zr(IV) sites. Compounds 1 and 2 are hydrolytically stable and catalyze the epoxidation of CC bonds in unfunctionalized alkenes and α,β-unsaturated ketones, as well as sulfoxidation of thioethers. Monomer 1 is more active than dimer 2. Acid additives greatly accelerate the oxygenation reactions and increase oxidant utilization efficiency up to >99%. Product distributions are indicative of a heterolytic oxygen transfer mechanism that involves electrophilic oxidizing species formed upon the interaction of Zr-POM and H 2 O 2 . The interaction of 1 and 2 with H 2 O 2 and the resulting peroxo derivatives have been investigated by UV−vis, FTIR, Raman spectroscopy, HR-ESI-MS, and combined HPLC-ICPatomic emission spectroscopy techniques. The interaction between an 17 O-enriched dimer, (Bu 4 N) 6 [{W 5 O 18 Zr(μ-OCH 3 )} 2 ] (2′), and H 2 O 2 was also analyzed by 17 O NMR spectroscopy. Combining these experimental studies with DFT calculations suggested the existence of dimeric peroxo species [(μ-η 2 :η 2 -O 2 ){ZrW 5 O 18 } 2 ] 6− as well as monomeric Zr-hydroperoxo [W 5 O 18 Zr(η 2 -OOH)] 3− and Zr-peroxo [HW 5 O 18 Zr(η 2 - O 2 )] 3− species. Reactivity studies revealed that the dimeric peroxo is inert toward alkenes but is able to transfer oxygen atoms to thioethers, while the monomeric peroxo intermediate is capable of epoxidizing CC bonds. DFT analysis of the reaction mechanism identifies the monomeric Zr-hydroperoxo intermediate as the real epoxidizing species and the corresponding α-oxygen transfer to the substrate as the rate-determining step. The calculations also showed that protonation of Zr-POM significantly reduces the free-energy barrier of the key oxygen-transfer step because of the greater electrophilicity of the catalyst and that dimeric species hampers the approach of alkene substrates due to steric repulsions reducing its reactivity. The improved performance of the Zr(IV) catalyst relative to Ti(IV) and Nb(V) catalysts is respectively due to a flexible coordination environment and a low tendency to form energy deep-well and low-reactive Zr-peroxo intermediates.

Nb-monosubstituted Lindqvist-type polyoxometalates (POM), (Bu4N)4[(NbW5O18)2O] (1) and (Bu4N)3[Nb­(O)­W5O18] (2), catalyze epoxidation of alkenes with hydrogen peroxide and mimic the catalytic performance of heterogeneous Nb-silicate catalysts. Dimer 1 is more active than monomer 2, but the catalytic activity of the latter increases in the presence of acid. Kinetic and spectroscopic studies suggest a mechanism that involves generation of monomer (Bu4N)2[Nb­(OH)­W5O18] (3), interaction of 3 with H2O2 leading to a protonated peroxo niobium species, (Bu4N)2[HNb­(O2)­W5O18] (4), followed by oxygen transfer to a CC bond in alkene. The previously unknown peroxo complex 4 has been isolated and characterized by elemental analysis; UV–vis, FT-IR, Raman, 93Nb, 17O and 183W NMR spectroscopy; cyclic voltammetry; and potentiometric titration. The physicochemical techniques support a monomeric Lindqvist structure of 4 bearing one peroxo ligand attached to Nb­(V) in a η2-coordination mode. While the unprotonated peroxo complex (Bu4N)3[Nb­(O2)­W5O18] (5) is inert toward alkenes under stoichiometric conditions, 4 readily reacts with cyclohexene to afford epoxide and 1,2-trans-cyclohexane diol, which proves the key role of protons for heterolytic activation of H2O2 over Nb­(V). The IR, Raman, UV–vis, and 17O NMR spectroscopic studies along with DFT calculations showed that the activating proton in 4 is predominantly located at a Nb–O–W bridging oxygen. However, DFT calculations revealed that the protonated peroxo species “HNb­(O2)” is present in equilibrium with a hydroperoxo species “Nb­(η2-OOH),” which has a lower activation barrier for the oxygen transfer to cyclohexene and is, therefore, the main epoxidizing species. The calculations indicate that protonation is crucial to generating the active species and to increasing POM electrophilicity.

Abstract:The molecular interactions between the Ce(IV)-substituted Keggin anion [PW11O39Ce(OH2)4] 3-(CeK) and hen egg white lysozyme (HEWL), was investigated by molecular dynamics (MD) simulations. We compared the analysis of CeK with the Ce(IV)-substituted Keggin dimer [(PW11O39)2Ce] 10-(CeK2) and the Zr(IV)-substituted Lindqvist anion [W5O18Zr(OH2)(OH)] 3-(ZrL) in order to understand how POM features such as the shape, the size, the charge or the type of incorporated metal ion influence the POM···protein interactions. Simulations revealed two regions of the protein, in which the CeK anion interacts strongly: the cationic sites formed by Arg21 on one hand and by Arg45 and Arg68 on the other. The two sites can be related with the observed selectivity in the hydrolytic cleavage of HEWL. The POMs chiefly interact with the side chains of the positively charged (arginines and lysines) and the polar uncharged (tyrosines, serines and aspargines) residues via electrostatic attraction and hydrogen bonding with the oxygens of the POM framework. The CeK anion shows higher protein affinity than the CeK2 and ZrL anions, because it is less hydrophilic and it has the right size and shape for stablishing interactions with several residues simultaneously. The larger and more negatively charged CeK2 anion has a high solvent-accessible surface, which is suboptimal for the interaction, while the smaller ZrL anion is highly hydrophilic and it cannot interact simultaneously with several residues so efficiently.

The influence of the composition of chaotropic polyoxometalate (POM)a nions on their affinity to biological systems was studied by meanso fa tomistic molecular dynamics (MD)s imulations. The variations in the affinity to hen egg-white lysozyme (HEWL) were analyzed along two series of POMs whereby the charge or the size and shape of the metal cluster are modified systematically.O ur simulations revealed aq uadratic relationship between the chargeo ft he POM and its affinity to HEWL as ac onsequence of the parabolic growth of POM···water interaction with the charge. As the chargei ncreases,P OMs becomel essc haotropic (more kosmotropic)i ncreasing the number and the strengtho f POM-water hydrogen bonds and structuringt he solvation shell aroundt he POM. This atomistic description explains the proportionally larger desolvation energies and less protein affinity for highly charged POMs, and consequently,t he preference for moderate charged ensities( q/M = 0.33). Also, our simulations suggest that POM···protein interactions are size-specific. The cationic pockets of HEWL protein show a preference for Keggin-like structures, which display the optimal dimensions ( % 1nm). Finally,w ed eveloped aq uantitative multidimensional model for protein affinity with predictive ability (r 2 = 0.97; q 2 = 0.88) using two molecular descriptors that account for the charge density (charge per metal atom ratio; q/M)a nd the size and shape (shape weightedvolume; V S ).

Ti- and Nb-monosubstituted tungstates of the Lindqvist structure, (Bu4N)3[(CH3O)­TiW5O18] (TiW 5 ) and (Bu4N)2[(CH3O)­NbW5O18] (NbW 5 ), display catalytic reactivity analogous to that of heterogeneous Ti- and Nb-containing catalysts in alkene oxidation with aqueous hydrogen peroxide. In this work, we make an attempt to rationalize the differences observed in the catalytic performance of Ti and Nb single-site catalysts for alkene epoxidation with H2O2 using MW 5 (M = Ti and Nb) as tractable molecular models. In the oxidation of cyclohexene, NbW 5 reveals higher catalytic activity and heterolytic pathway selectivity than its Ti counterpart, while TiW 5 is more active for decomposition of H2O2. The heterolytic and homolytic oxidation pathways have been investigated by means of kinetic and computational tools. The kinetic trends established for MW 5 -catalyzed epoxidation, comparative spectroscopic studies (IR, Raman, UV–vis, and 1H and 17O NMR) of the reaction between MW 5 and hydrogen peroxide, and DFT calculations implemented on cyclohexene epoxidation over MW 5 strongly support a mechanism that involves interaction of either MW 5 or its hydrolyzed form “MOH” with H2O2 to afford a protonated peroxo species “HMO2” that is present in equilibrium with a hydroperoxo species “MOOH”, followed by electrophilic oxygen atom transfer from “MOOH” to the CC bond to give epoxide and “MOH”. For both Ti and Nb, the peroxo species “HMO2” is more stable than the hydroperoxo species “MOOH”, but the latter is more reactive toward alkenes. For the Ti catalyst, which has a rigid and hindered metal center, the hydroperoxo species transfers preferentially the nondistorted β-oxygen, whereas for the Nb catalyst the transference of the more electrophilic α-oxygen is favored. Moreover, upon increasing the oxidation state from Ti­(IV) to Nb­(V), the reaction accelerates and selectivity toward electrophilic products increases. Calculations showed that the Nb­(V) catalyst reduces significantly the free-energy barrier for the heterolytic oxygen transfer because of the higher electrophilicity of the metal center. The improved performance of the Nb­(V) single site is due to a combination of a flexible coordination environment with a higher metal oxidation state.