Moving protons with pendant amines: proton mobility in a nickel catalyst for oxidation of hydrogen

Proton transport is ubiquitous in chemical and biological processes, including the reduction of dioxygen to water, the reduction of CO(2) to formate, and the production/oxidation of hydrogen. In this work we describe intramolecular proton transfer between Ni and positioned pendant amines for the hydrogen oxidation electrocatalyst [Ni(P(Cy)(2)N(Bn)(2)H)(2)](2+) (P(Cy)(2)N(Bn)(2) = 1,5-dibenzyl-3,7-dicyclohexyl-1,5-diaza-3,7-diphosphacyclooctane). Rate constants are determined by variable-temperature one-dimensional NMR techniques and two-dimensional EXSY experiments. Computational studies provide insight into the details of the proton movement and energetics of these complexes. Intramolecular proton exchange processes are observed for two of the three experimentally observable isomers of the doubly protonated Ni(0) complex, [Ni(P(Cy)(2)N(Bn)(2)H)(2)](2+), which have N-H bonds but no Ni-H bonds. For these two isomers, with pendant amines positioned endo to the Ni, the rate constants for proton exchange range from 10(4) to 10(5) s(-1) at 25 °C, depending on isomer and solvent. No exchange is observed for protons on pendant amines positioned exo to the Ni. Analysis of the exchange as a function of temperature provides a barrier for proton exchange of ΔG(?) = 11-12 kcal/mol for both isomers, with little dependence on solvent. Density functional theory calculations and molecular dynamics simulations support the experimental observations, suggesting metal-mediated intramolecular proton transfers between nitrogen atoms, with chair-to-boat isomerizations as the rate-limiting steps. Because of the fast rate of proton movement, this catalyst may be considered a metal center surrounded by a cloud of exchanging protons. The high intramolecular proton mobility provides information directly pertinent to the ability of pendant amines to accelerate proton transfers during catalysis of hydrogen oxidation. These results may also have broader implications for proton movement in homogeneous catalysts and enzymes in general, with specific implications for the proton channel in the Ni-Fe hydrogenase enzyme.     

The role of pendant amines in the breaking and forming of molecular hydrogen catalyzed by nickel complexes

We present the results of a comprehensive theoretical investigation of the role of pendant amine ligands in the oxidation of H(2) and formation of H(2) by [Ni(P(R)(2)N(R')(2))(2)](2+) electrocatalysts (P(R)(2)N(R')(2) is the 1,5-R'-3,7-R derivative of 1,5-diaza-3,7-diphosphacyclooctane, in which R and R' are aryl or alkyl groups). We focus our analysis on the thermal steps of the catalytic cycle, as they are known to be rate-determining for both H(2) oxidation and production. We find that the presence of pendant amine functional groups greatly facilitates the heterolytic H(2) bond cleavage, resulting in a protonated amine and a Ni hydride. Only one single positioned pendant amine is required to serve this function. The pendant amine can also effectively shuttle protons to the active site, making the redistribution of protons and the H(2) evolution a very facile process. An important requirement for the overall catalytic process is the positioning of at least one amine in close proximity to the metal center. Indeed, only protonation of the pendant amines on the metal center side (endo position) leads to catalytically active intermediates, whereas protonation on the opposite side of the metal center (exo position) leads to a variety of isomers, which are detrimental to catalysis.     

Carbon-sulfur bond cleavage in Bis(N-alkyldithiocarbamato)cadmium(II) complexes: heterolytic desulfurization coupled to topochemical proton transfer

Three bis(N-alkyldithiocarbamato)cadmium(II) complexes [Cd(S(2)CNHR)(2)] (1, R = n-C(3)H(7); 2, R = n-C(5)H(11); 3, n-C(12)H(25)) were prepared by metathesis of the corresponding lithium salt, Li[S(2)CNHR], with cadmium chloride. The crystal structures of 2 and 3 consist of planar molecular units of [Cd(S(2)CNHR)(2)] connected by intermolecular Cd.S interactions to give a one-dimensional chain. The chains are connected by a network of intermolecular N-H.S hydrogen bonds between the dithiocarbamato nitrogen atom and bridging sulfur atoms in neighboring chains. In solution, the (113)Cd NMR spectrum of 2 is dependent on concentration and temperature, indicative of a dimerization equilibrium mediated by similar Cd.S intermolecular bridging interactions. In the solid state, thermal gravimetric analyses show that all three complexes decompose smoothly via a heterolytic C-S bond cleavage reaction to give the corresponding alkyl isothiocyanate and cadmium sulfide as the primary products, with the formation of primary amine and CS(2) as coproducts. These products can result only from the net transfer of protons between N-alkyldithiocarbamato ligands in the solid state. Thus, the C-S bond cleavage reaction is interpreted in terms of the topochemical arrangement of molecular units in the crystalline state, which provides a pathway for proton transfer between ligands via N-H.S hydrogen bonds. Decomposition was also initiated by addition of a tertiary amine to a solution of [Cd(S(2)CNHR)(2)]. This confirms that C-S bond cleavage must be coupled to deprotonation of the -NH group, and explains why dialkylated derivatives [Cd(S(2)CNR(2))(2)] are inert to this particular mode of C-S bond cleavage. This system thus constitutes an unusual example of heterolytic, nonoxidative C-S bond cleavage that appears to proceed by a topochemical transfer of protons, which has implications for C-S bond cleavage processes in single-source precursors for II-VI semiconductor materials.     

Selective Formation of an FeIVO or an FeIIIOOH Intermediate From Iron(II) and H2O2: Controlled Heterolytic versus Homolytic Oxygen–Oxygen Bond Cleavage by the Second Coordination Sphere

We demonstrate that the devised incorporation of an alkylamine group into the second coordination sphere of an Fe^II complex allows to switch its reactivity with H₂O₂ from the usual formation of Fe^III species towards the selective generation of an Fe^IV‐oxo intermediate. The Fe^IV‐oxo species was characterized by UV/Vis absorption and Mössbauer spectroscopy. Variable‐temperature kinetic analyses point towards a mechanism in which the heterolytic cleavage of the O?O bond is triggered by a proton transfer from the proximal to the distal oxygen atom in the Fe^II‐H₂O₂ complex with the assistance of the pendant amine. DFT studies reveal that this heterolytic cleavage is actually initiated by an homolytic O?O cleavage immediately followed by a proton‐coupled electron transfer (PCET) that leads to the formation of the Fe^IV‐oxo and release of water through a concerted mechanism.     

Proton exchanges between phenols and ammonia or amines: a computational study

Density functional theory calculations at the B3LYP/6-31+G(d,p) level of theory have been performed to explore proton exchanges between phenols and ammonia or amines, which can be used to account for previous NMR experiments. For the parent phenol-NH(3) system, a transition state with a symmetric phenolate-NH(4)(+)-like structure, which lies about 35 kcal mol(-1) in energy above the hydrogen-bonded complex, has been successfully located. An intrinsic reaction coordinate (IRC) analysis indicates that the proton exchange is a concerted process, which can be roughly divided into four continuous subprocesses. A series of para-substituted phenol-NH(3) systems have been considered to investigate the substituent effect. Whereas introduction of an electron-withdrawing group on the phenol appreciably reduces the barrier, an opposite effect is observed for an electron-donating group. Moreover, it has been disclosed that there exists a good linear correlation between the activation barriers and the interaction energies between the phenols and NH(3), indicating the important role of proton transfer (or hydrogen bonding) in determining the proton exchange. Also considered are the proton exchanges between phenol and amines and those for some sterically hindered systems. The results show that the phenol tends to exchange hydrogen with the amines, preferably the secondary amines, and that the steric effect is favorable for the proton exchange, which imply that, as the IRC analysis suggested, besides the proton transfer, the flip of the ammonium-like moiety may play a significant role in the course of proton exchange. For all of these systems, we investigated the solvent effects and found that the barrier heights of proton exchange decrease remarkably as compared to those in a vacuum due to the ion pair feature of the transition state. Finally, we explored the phenol radical cation-NH(3) system; the barrierless proton transfer and remarkably low barrier (5.2 kcal mol(-1)) of proton exchange provide further evidence for the importance of proton transfer in the proton exchange.     

HCN→HNC异构化反应过渡态附近的拓扑特性

电荷密度拓扑分析方法(topological analysis of charge distribution)已经被广泛应用于研究化合物的各种静态性质及反应特性.对IRC反应途径上过渡态附近构型的拓扑性质研究报导较少.本工作是用电荷密度分布的拓扑分析方法对HCN→HNC异构化反应IRC过渡态附近的性质进行了研究.对电荷密度分布拓扑分析和IRC途径确定选用相同的基组,得到了一些新的结论。     

Homolytic versus Heterolytic Hydrogen Evolution Reaction Steered by a Steric Effect

Several H?H bond forming pathways have been proposed for the hydrogen evolution reaction (HER). Revealing these HER mechanisms is of fundamental importance for the rational design of catalysts and is also extremely challenging. Now, an unparalleled example of switching between homolytic and heterolytic HER mechanisms is reported. Three nickel(II) porphyrins were designed and synthesized with distinct steric effects by introducing bulky amido moieties to ortho‐ or para‐positions of the meso‐phenyl groups. These porphyrins exhibited different catalytic HER behaviors. For these Ni porphyrins, although their 1e‐reduced forms are active to reduce trifluoroacetic acid, the resulting Ni hydrides (depending on the steric effects of porphyrin rings) have different pathways to make H₂. Understanding HER processes, especially controllable switching between homolytic and heterolytic H?H bond formation pathways through molecular engineering, is unprecedented in electrocatalysis.     

Studies of a series of [Ni(P(R)2N(Ph)2)2(CH3CN)]2+ complexes as electrocatalysts for H2 production: substituent variation at the phosphorus atom of the P2N2 ligand

A series of [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes containing the cyclic diphosphine ligands [P(R)(2)N(Ph)(2) = 1,5-diaza-3,7-diphosphacyclooctane; R = benzyl (Bn), n-butyl (n-Bu), 2-phenylethyl (PE), 2,4,4-trimethylpentyl (TP), and cyclohexyl (Cy)] have been synthesized and characterized. X-ray diffraction studies reveal that the cations of [Ni(P(Bn)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) and [Ni(P(n-Bu)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) have distorted trigonal bipyramidal geometries. The Ni(0) complex [Ni(P(Bn)(2)N(Ph)(2))(2)] was also synthesized and characterized by X-ray diffraction studies and shown to have a distorted tetrahedral structure. These complexes, with the exception of [Ni(P(Cy)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2), all exhibit reversible electron transfer processes for both the Ni(II/I) and Ni(I/0) couples and are electrocatalysts for the production of H(2) in acidic acetonitrile solutions. The heterolytic cleavage of H(2) by [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes in the presence of p-anisidine or p-bromoaniline was used to determine the hydride donor abilities of the corresponding [HNi(P(R)(2)N(Ph)(2))(2)](BF(4)) complexes. However, for the catalysts with the most bulky R groups, the turnover frequencies do not parallel the driving force for elimination of H(2), suggesting that steric interactions between the alkyl substituents on phosphorus and the nitrogen atom of the pendant amines play an important role in determining the overall catalytic rate.     

Amidolithium and amidoaluminum catalyzed synthesis of substituted guanidines: an interplay of DFT modeling and experiment

The synthesis of substituted guanidines is of significant interest for their use as versatile ligands and for the synthesis of bioactive molecules. Lithium amides supported by tetramethylethylenediamine have recently been shown to catalyze the guanylation of amines with carbodiimide. In this report, density functional theory (DFT) calculations are used to provide insight into the mechanism of this transformation. The mechanism identified through our calculations is a carbodiimide insertion into the lithium-amide bond to form a lithium guanidinate, followed by a proton transfer from the amine. The proton transfer transition state requires the dissociation of one of the chelating nitrogen centers of the lithium guanidinate, proton abstraction from the amine, and bond formation between the lithium center and the amine nitrogen. On the basis of this mechanism, further calculations predicted that aluminum amides would also function as active catalysts for the guanylation of amines. We confirm this experimentally and report the development of aluminum amides as a new main group catalyst for the guanylation of a range of electron-poor amines with carbodiimide.     

Proton-shuffle mechanism of O-O activation for formation of a high-valent oxo-iron species of bleomycin

Bleomycins (BLMs) can utilize H2O2 to cleave DNA in the presence of ferric ions. DFT calculations were used to study the mechanism of O-O bond cleavage in the low-spin FeIII-hydroperoxo complex of BLM. The following alternative hypotheses were investigated using realistic structural models: (a) heterolytic cleavage of the O-O bond, generating a Compound I (Cpd I) like intermediate, formally BLM-FeV=O; (b) homolytic O-O cleavage, leading to a BLM-FeIV=O species and an OH* radical; and (c) a direct O-O cleavage/H-abstraction mechanism by ABLM. The calculations showed that (a) is a facile and viable mechanism; it involves acid-base proton reshuffle mediated by the side-chain linkers of BLM, causing thereby heterolytic cleavage of the O-O bond and generation of Cpd I. Formation of Cpd I is found to involve a barrier of 13.3 kcal/mol, which is lower than the barriers in the alternative mechanisms (b and c) that possess respective barriers of 31 and 17 kcal/mol. The so-formed Cpd I species with a radical on the side-chain linker, methylvalerate (V), adjacent to the BLM-FeIV=O complex, resembles the formation of the active species of cytochrome c peroxidase in the Poulos-Kraut proton-shuffle mechanism in heme peroxidases (Poulos, T. L.; Kraut, J. J. Biol. Chem. 1980, 255, 8199-8205). Experimental data are discussed and shown to be in accord with this proposal. It suggests that the high-valence Cpd I species of BLM participates in the DNA cleavage. This is an alternative mechanistic hypothesis to the exclusive reactivity scenario based on ABLM (FeIII-OOH).     

Theory of hydride-proton transfer (HPT) carbonyl reduction by [Os(III)(tpy)(Cl)(NH═CHCH(3))(NSAr)

Quantum mechanical analysis reveals that carbonyl reduction of aldehydes and ketones by the imine-based reductant cis-[Os(III)(tpy)(Cl)(NH═CHCH(3))(NSAr)] (2), which is accessible by reduction of the analogous nitrile, occurs by hydride-proton transfer (HPT) involving both the imine and sulfilimido ligands. In carbonyl reduction, water or alcohol is necessary to significantly lower the barrier for proton shuttling between ligands. The -N(H)SAr group activates the carbonyl group through hydrogen bonding while the -NC(H)CH(3) ligand delivers the hydride.     

Disulfide Bond Cleavage: A Redox Reaction Without Electron Transfer

By using Car–Parrinello molecular dynamics (CPMD) simulations we have simulated a mechanically induced redox reaction. Previous single‐molecule atomic force microscopy (AFM) experiments demonstrated that the reduction of disulfide bonds in proteins with the weak reducing agent dithiothreitol depends on a mechanical destabilization of the breaking bond. With reactive molecular dynamics simulations the single steps of the reaction mechanism can be elucidated and the motion of the electrons can be monitored. The simulations show that the redox reaction consists of the heterolytic cleavage of the S? S bond followed by a sequence of proton transfers.     

The Poulos-Kraut mechanism of Compound I formation in horseradish peroxidase: a QM/MM study

QM/MM calculations are used to elucidate the Poulos-Kraut (Poulos, T. L.; Kraut, J. J. Biol. Chem. 1980, 255, 8199-8205) mechanism of O-O bond activation and Compound I (Cpd I) formation in HRP, in conditions corresponding to neutral to basic pH. Attempts to generate Compound I directly from the Fe(H2O2) complex by migrating the proton from the proximal oxygen to the distal one (1,2- proton shift) result in high barriers. The lowest energy mechanism was found to involve initial deprotonation of ferric hydrogen peroxide complex (involving spin crossover from the quartet to the doublet state) by His42 to form ferric-hydroperoxide (Cpd 0). Subsequently, the distal OH group of Cpd 0 is pulled by Arg38 and reprotonated by His42(H+) to form Cpd I and a water molecule that bridges the two residues. The structures of the intermediate and the transition state reveal the manner by which the Arg-His residues promote cooperatively the electronic reorganization that is required to attend the heterolytic O-O cleavage.     

Mononuclear [NiII(L)(P-(o-C6H4S)2(o-C6H4SH))]0/1- (L = thiolate, selenolate, PPh3, and Cl) complexes with intramolecular [Ni...S...H...S]/[Ni...H...S] interactions modulated by the coordinated ligand L: relevance to the [NiFe] hydrogenases

The shift of the IR nu(S)(-)(H) frequency to lower wavenumbers for the series of complexes [Ni(II)(L)(P-(o-C6H4S)2(o-C6H4SH))]0/1- (L = PPh3 (1), Cl (6), Se-p-C6H4-Cl (5), S-C4H3S (7), SePh (4)) indicates that a trend of increasing electronic donation of the L ligands coordinated to the Ni(II) center promotes intramolecular [Ni-S...H-S] interactions. Compared to the Ni...S(H) distance, in the range of 3.609-3.802 A in complexes 1 and 4-7, the Ni...S(CH3) distances of 2.540 and 2.914 A observed in the [Ni(II)(PPh3)(P(o-C6H4S)2(o-C6H4-SCH3))] complexes (8a and 8b, two conformational isomers with the chemical shift of the thioether methyl group at delta 1.820 (-60 degrees C) and 2.109 ppm (60 degrees C) (C4D8O)) and the Ni...S(CH3) distances of 3.258 and 3.229 A found in the [Ni(II)(L)(P(o-C6H4S)2(o-C6H4-SCH3))]1- complexes (L = SPh (9), SePh (10)) also support the idea that the pendant thiol protons of the Ni(II)-thiol complexes 1/4-7 were attracted by both the sulfur of thiolate and the nickel. The increased basicity (electronic density) of the nickel center regulated by the monodentate ligand attracted the proton of the pendant thiol effectively and caused the weaker S...H bond. In addition, the pendant thiol interaction modes in the solid state (complexes 1a and 1b, Scheme 1) may be controlled by the solvent of crystallization. Compared to complex 1a, the stronger intramolecular [Ni-S...H-S] interaction (or a combination of [Ni-S...H-S]/[Ni...H-S] interactions) found in complexes 4-7 led to the weaker S-H bond strength and accelerated the oxidation (by O2) of complexes 4-7 to produce the [Ni(Y)(L)(P(o-C6H4S)3)]1- (L = Se-p-C6H4-Cl (11), SePh (12), S-C4H3S (13)) complexes.     

Analysis of the activation and heterolytic dissociation of H2 by frustrated Lewis pairs: NH3/BX3 (X = H, F, and Cl)

We performed a computational study of H(2) activation and heterolytic dissociation promoted by prototype Lewis acid/base pairs NH(3)/BX(3) (X = H, F, and Cl) to understand the mechanism in frustrated Lewis pairs (FLPs). Although the NH(3)/BX(3) pairs form strong dative bonds, electronic structure theories make it possible to explore the potential energy surface away from the dative complex, in regions relevant to H(2) activation in FLPs. A weakly bound precursor complex, H(3)N·H(2)·BX(3), was found in which the H(2) molecule interacts side-on with B and end-on with N. The BX(3) group is pyramidal in the case of X = H, similar to the geometry of BH(5), but planar in the complexes with X = F and Cl. The latter complexes convert to ion pairs, [NH(4)(+)][BHX(3)(-)] with enthalpy changes of 7.3 and -9.4 kcal/mol, respectively. The minimum energy paths between the FLP and the product ion pair of the chloro and fluoro complexes were calculated and analyzed in great detail. At the transition state (TS), the H(2) bond is weakened and the BX(3) moiety has undergone significant pyramidal distortion. As such, the FLP is prepared to accept the incipient proton and hydride ion on the product-side. The interaction energy of the H(2) with the acid/base pair and the different contributions for the precursor and TS complex from an energy decomposition analysis expose the dominant factors affecting the reactivity. We find that structural reorganization of the precursor complex plays a significant role in the activation and that charge-transfer interactions are the dominant stabilizing force in the activated complex. The electric field clearly has a role in polarizing H(2), but its contribution to the overall interaction energy is small compared to that from the overlap of the p(N), σ(H-H), σ*(H-H), and p(B) orbitals at the TS. Our detailed analysis of the interaction of H(2) with the FLP provides insight into the important components that should be taken into account when designing related systems to activate H(2).     

Explanation for main features of structure-genotoxicity relationships of aromatic amines by theoretical studies of their activation pathways in CYP1A2

Aromatic and heteroaromatic amines (ArNH(2)) represent a class of potential mutagens that after being metabolically activated covalently modify DNA. Activation of ArNH(2) in many cases starts with N-hydroxylation by P450 enzymes, primarily CYP1A2. Poor understanding of structure-mutagenicity relationships of ArNH(2) limits their use in drug discovery programs. Key factors that facilitate activation of ArNH(2) are revealed by exploring their reaction intermediates in CYP1A2 using DFT calculations. On the basis of these calculations and extensive analysis of structure-mutagenicity data, we suggest that mutagenic metabolites are generated by ferric peroxo intermediate, (CYP1A2)Fe(III)-OO(-), in a three-step heterolytic mechanism. First, the distal oxygen of the oxidant abstracts proton from H-bonded ArNH(2). The subsequent proximal protonation of the resulting (CYP1A2)Fe(III)-OOH weakens both the O-O and the O-H bonds of the oxidant. Heterolytic cleavage of the O-O bond leads to N-hydroxylation of ArNH(-) via S(N)2 mechanism, whereas cleavage of the O-H bond results in release of hydroperoxy radical. Thus, our proposed reaction offers a mechanistic explanation for previous observations that metabolism of aromatic amines could cause oxidative stress. The primary drivers for mutagenic potency of ArNH(2) are (i) binding affinity of ArNH(2) in the productive binding mode within the CYP1A2 substrate cavity, (ii) resonance stabilization of the anionic forms of ArNH(2), and (iii) exothermicity of proton-assisted heterolytic cleavage of N-O bonds of hydroxylamines and their bioconjugates. This leads to a strategy for designing mutagenicity free ArNH(2): Structural alterations in ArNH(2), which disrupt geometric compatibility with CYP1A2, hinder proton abstraction, or strongly destabilize the nitrenium ion, in this order of priority, prevent genotoxicity.     

Heterolytic activation of H-X (X = H, Si, B, and C) bonds: an experimental and theoretical investigation

The highly electrophilic, coordinatively unsaturated, 16-electron [Ru(P(OH)3)(dppe)2][OTf]2 (dppe = Ph2PCH2CH2PPh2) complex 1 activates the H-H, the Si-H, and the B-H bonds, in H2(g), EtMe2SiH and Et3SiH, and H3B.L (L = PMe3, PPh3), respectively, in a heterolytic fashion. The heterolysis of H2 involves an eta2-H2 complex (observable at low temperatures), whereas the computations indicate that those of the Si-H and the B-H bonds proceed through unobserved eta1-species. The common ruthenium-containing product in these reactions is trans-[Ru(H)(P(OH)3)(dppe)2][OTf], 2. The [Ru(P(OH)3)(dppe)2][OTf]2 complex is unique with regard to activating the H-H, the Si-H, and the B-H bonds in a heterolytic manner. These reactions and the heterolytic activation of the C-H bond in methane by the model complex [Ru(POH)3)(H2PCH2CH2PH2)2][Cl][OTf], 4, have been investigated using computational methods as well, at the B3LYP/LANL2DZ level. While the model complex activates the H-H, the Si-H, and the B-H bonds in H2, SiH4, and H3B.L (L = PMe3, PPh3), respectively, with a low barrier, activation of the C-H bond in CH4 involves a transition state of 57.5 kcal/mol high in energy. The inability of the ruthenium complex to activate CH4 is due to the undue stretching of the C-H bond needed at the transition state, in comparison to the other substrates.     

Heterolytic Cleavage of Hydrogen by an Iron Hydrogenase Model: An Fe‐H⋅⋅⋅H‐N Dihydrogen Bond Characterized by Neutron Diffraction

Hydrogenase enzymes in nature use hydrogen as a fuel, but the heterolytic cleavage of H? H bonds cannot be readily observed in enzymes. Here we show that an iron complex with pendant amines in the diphosphine ligand cleaves hydrogen heterolytically. The product has a strong Fe‐H???H‐N dihydrogen bond. The structure was determined by single‐crystal neutron diffraction, and has a remarkably short H???H distance of 1.489(10) Å between the protic N‐H^δ+ and hydridic Fe‐H^δ? part. The structural data for [CpFe H (P^tBu₂N^tBu₂ H )]⁺ provide a glimpse of how the H? H bond is oxidized or generated in hydrogenase enzymes. These results now provide a full picture for the first time, illustrating structures and reactivity of the dihydrogen complex and the product of the heterolytic cleavage of H₂ in a functional model of the active site of the [FeFe] hydrogenase enzyme.     

Stereochemistry and mechanism of the Brønsted acid catalyzed intramolecular hydrofunctionalization of an unactivated cyclic alkene

Through employment of deuterium-labeled substrates, the triflic acid catalyzed intramolecular exo addition of the X-H(D) (X=N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the C=C bond of a pendant cyclohexene moiety was found to occur, in each case, with exclusive formation (≥90%) of the anti-addition product without loss or scrambling of deuterium as determined by (1)H and (2)H NMR spectroscopy and mass spectrometry analysis. Kinetic analysis of the triflic-acid-catalyzed intramolecular hydroamination of N-(2-cyclohex-2'-enyl-2,2-diphenylethyl)-p-toluenesulfonamide (1a) established the second-order rate law: rate=k(2)[HOTf][1a] and the activation parameters ΔH(++)=(9.7±0.5) kcal mol(-1) and ΔS(++)=(-35±5) cal K(-1) mol(-1). An inverse α-secondary kinetic isotope effect of k(D)/k(H) =(1.15±0.03) was observed upon deuteration of the C2' position of 1a, consistent with partial C-N bond formation in the highest energy transition state of catalytic hydroamination. The results of these studies were consistent with a mechanism for the intramolecular hydroamination of 1a involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C3' position of 1a coupled with intramolecular anti addition of the pendant sulfonamide nitrogen atom to the alkenyl C2' position.