Sequential Proton Transfer Research Articles

Enzyme That Makes You Cry-Crystal Structure of Lachrymatory Factor Synthase from Allium cepa.

The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFS in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.

Excited-State Properties of Protochlorophyllide Analogues and Implications for Light-Driven Synthesis of Chlorophyll.

Protochlorophyllide (Pchlide), an intermediate in the biosynthesis of chlorophyll, is the substrate for the light-driven enzyme protochlorophyllide oxidoreductase. Pchlide has excited-state properties that allow it to initiate photochemistry in the enzyme active site, which involves reduction of Pchlide by sequential hydride and proton transfer. The basis of this photochemical behavior has been investigated here using a combination of time-resolved spectroscopies and density functional theory calculations of a number of Pchlide analogues with modifications to various substituent groups. A keto group on ring E is essential for excited-state charge separation in the molecule, which is the driving force for the photoreactivity of the pigment. Vibrational "fingerprints" of specific regions of the Pchlide chromophore have been assigned, allowing identification of the modes that are crucial for excited-state chemistry in the enzyme. This work provides an understanding of the structural determinants of Pchlide that are important for harnessing light energy.

Concerted double proton-transfer electron-transfer between catechol and superoxide radical anion.

We have carried out a computational study on the reactivity of catechol (1,2-dihydroxybenzene) towards superoxide radical anion (O2˙-) in water, N,N-dimethylformamide (DMF), pentyl ethanoate (PEA) and vacuum using density functional theory and the coupled cluster method. Five reaction mechanisms were studied: (i) sequential proton transfer followed by hydrogen atom transfer (PT-HT), (ii) sequential hydrogen atom transfer followed by proton transfer (HT-PT), (iii) single electron transfer (SET), (iv) radical adduct formation (RAF) and (v) concerted double proton-transfer electron-transfer (denoted as global reaction, GR). Our results show that catechol and superoxide do not react via a sequential reaction mechanism (initial PT, initial HAT or SET). Instead, the reaction proceeds via a concerted double proton-transfer electron-transfer mechanism yielding hydrogen peroxide and catechol radical anion. The protons are transferred asynchronously between the σ orbitals of the catechol oxygen atoms to superoxide, while the electron is transferred between oxygen π orbitals in the same direction. The calculated rate constants in aqueous media agree with the experimental values reported in the literature. This suggests that the mechanism proposed in this work is adequate to describe this reaction. In addition, our results show that the reaction exhibits a large tunneling effect.

Sequential and Coupled Proton and Electron Transfer Events in the S2 → S3 Transition of Photosynthetic Water Oxidation Revealed by Time-Resolved X-ray Absorption Spectroscopy.

The choreography of electron transfer (ET) and proton transfer (PT) in the S-state cycle at the manganese-calcium (Mn4Ca) complex of photosystem II (PSII) is pivotal for the mechanism of photosynthetic water oxidation. Time-resolved room-temperature X-ray absorption spectroscopy (XAS) at the Mn K-edge was employed to determine the kinetic isotope effect (KIE = τD2O/τH2O) of the four S transitions in a PSII membrane particle preparation in H2O and D2O buffers. We found a small KIE (1.2-1.4) for manganese oxidation by ET from Mn4Ca to the tyrosine radical (YZ•+) in the S0n → S1+ and S1n → S2+ transitions and for manganese reduction by ET from substrate water to manganese ions in the O2-evolving S3n → S0n step, but a larger KIE (∼1.8) for manganese oxidation in the S2n → S3+ step (subscript, number of accumulated oxidizing equivalents; superscript, charge of Mn4Ca). Kinetic lag phases detected in the XAS transients prior to the respective ET steps were assigned to S3+ → S3n (∼150 μs, H2O; ∼380 μs, D2O) and S2+ → S2n (∼25 μs, H2O; ∼120 μs, D2O) steps and attributed to PT events according to their comparatively large KIE (∼2.4, ∼4.5). Our results suggest that proton movements and molecular rearrangements within the hydrogen-bonded network involving Mn4Ca and its bound (substrate) water ligands and the surrounding amino acid/water matrix govern to different extents the rates of all ET steps but affect particularly strongly the S2n → S3+ transition, assigned as proton-coupled electron transfer. Observation of a lag phase in the classical S2 → S3 transition verifies that the associated PT is a prerequisite for subsequent ET, which completes Mn4Ca oxidation to the all-Mn(IV) level.

Cross-Species Analysis of Protein Dynamics Associated with Hydride and Proton Transfer in the Catalytic Cycle of the Light-Driven Enzyme Protochlorophyllide Oxidoreductase.

Experimental interrogation of the relationship between protein dynamics and enzyme catalysis is challenging. Light-activated protochlorophyllide oxidoreductase (POR) is an excellent model for investigating this relationship because photoinitiation of the reaction cycle enables coordinated turnover in a "dark-assembled" ternary enzyme-substrate complex. The catalytic cycle involves sequential hydride and proton transfers (from NADPH and an active site tyrosine residue, respectively) to the substrate protochlorophyllide. Studies with a limited cross-species subset of POR enzymes (n = 4) have suggested that protein dynamics associated with hydride and proton transfer are distinct [Heyes, D. J., Levy, C., Sakuma, M., Robertson, D. L., and Scrutton, N. S. (2011) J. Biol. Chem. 286, 11849-11854]. Here, we use steady-state assays and single-turnover laser flash spectroscopy to analyze hydride and proton transfer dynamics in an extended series of POR enzymes taken from many species, including cyanobacteria, algae, embryophytes, and angiosperms. Hydride/proton transfer in all eukaryotic PORs is faster compared to prokaryotic PORs, suggesting active site architecture has been optimized in eukaryotic PORs following endosymbiosis. Visible pump-probe spectroscopy was also used to demonstrate a common photoexcitation mechanism for representative POR enzymes from different branches of the phylogenetic tree. Dynamics associated with hydride transfer are localized to the active site of all POR enzymes and are conserved. However, dynamics associated with proton transfer are variable. Protein dynamics associated with proton transfer are also coupled to solvent dynamics in cyanobacterial PORs, and these networks are likely required to optimize (shorten) the donor-acceptor distance for proton transfer. These extended networks are absent in algal and plant PORs. Our analysis suggests that extended networks of dynamics are disfavored, possibly through natural selection. Implications for the evolution of POR and more generally for other enzyme catalysts are discussed.

Ultrafast Photoinduced Interfacial Proton Coupled Electron Transfer from CdSe Quantum Dots to 4,4'-Bipyridine.

Pyridine and derivatives have been reported as efficient and selective catalysts for the electrochemical and photoelectrochemical reduction of CO2 to methanol. Although the catalytic mechanism remains a subject of considerable recent debate, most proposed models involve interfacial proton coupled electron transfer (PCET) to electrode-bound catalysts. We report a combined experimental and theoretical study of the photoreduction of 4,4'-bipyridium (bPYD) using CdSe quantum dots (QDs) as a model system for interfacial PCET. We observed ultrafast photoinduced PCET from CdSe QDs to form doubly protonated [bPYDH2](+•) radical cations at low pH (4-6). Through studies of the dependence of PCET rate on isotopic substitution, pH and bPYD concentration, the radical formation mechanism was identified to be a sequential interfacial electron and proton transfer (ET/PT) process with a rate-limiting pH independent electron transfer rate constant, kint, of 1.05 ± 0.13 × 10(10) s(-1) between a QD and an adsorbed singly protonated [bPYDH](+). Theoretical studies of the adsorption of [bPYDH](+) and methylviologen on QD surfaces revealed important effects of hydrogen bonding with the capping ligand (3-mercaptopropionic acid) on binding geometry and interfacial PCET. In the presence of sacrificial electron donors, this system was shown to be capable of generating [bPYDH2](+•) radical cations under continuous illumination at 405 nm with a steady-state photoreduction quantum yield of 1.1 ± 0.1% at pH 4. The mechanism of bPYD photoreduction reported in this work may provide useful insights into the catalytic roles of pyridine and pyridine derivatives in the electrochemical and photoelectrochemical reduction of CO2.

Infrared Spectroscopy During Electrocatalytic Turnover Reveals the Ni‐L Active Site State During H2 Oxidation by a NiFe Hydrogenase

AbstractA novel in situ IR spectroscopic approach is demonstrated for the characterization of hydrogenase during catalytic turnover. E. coli hydrogenase 1 (Hyd‐1) is adsorbed on a high surface‐area carbon electrode and subjected to the same electrochemical control and efficient supply of substrate as in protein film electrochemistry during spectral acquisition. The spectra reveal that the active site state known as Ni‐L, observed in other NiFe hydrogenases only under illumination or at cryogenic temperatures, can be generated reversibly in the dark at ambient temperature under both turnover and non‐turnover conditions. The observation that Ni‐L is present at all potentials during turnover under H2 suggests that the final steps in the catalytic cycle of H2 oxidation by Hyd‐1 involve sequential proton and electron transfer via Ni‐L. A broadly applicable IR spectroscopic technique is presented for addressing electrode‐adsorbed redox enzymes under fast catalytic turnover.

Infrared Spectroscopy During Electrocatalytic Turnover Reveals the Ni-L Active Site State During H2 Oxidation by a NiFe Hydrogenase.

A novel in situ IR spectroscopic approach is demonstrated for the characterization of hydrogenase during catalytic turnover. E. coli hydrogenase 1 (Hyd-1) is adsorbed on a high surface-area carbon electrode and subjected to the same electrochemical control and efficient supply of substrate as in protein film electrochemistry during spectral acquisition. The spectra reveal that the active site state known as Ni-L, observed in other NiFe hydrogenases only under illumination or at cryogenic temperatures, can be generated reversibly in the dark at ambient temperature under both turnover and non-turnover conditions. The observation that Ni-L is present at all potentials during turnover under H2 suggests that the final steps in the catalytic cycle of H2 oxidation by Hyd-1 involve sequential proton and electron transfer via Ni-L. A broadly applicable IR spectroscopic technique is presented for addressing electrode-adsorbed redox enzymes under fast catalytic turnover.

Conditional Born-Oppenheimer Dynamics: Quantum Dynamics Simulations for the Model Porphine.

We report a new theoretical approach to solve adiabatic quantum molecular dynamics halfway between wave function and trajectory-based methods. The evolution of a N-body nuclear wave function moving on a 3N-dimensional Born-Oppenheimer potential-energy hyper-surface is rewritten in terms of single-nuclei wave functions evolving nonunitarily on a 3-dimensional potential-energy surface that depends parametrically on the configuration of an ensemble of generally defined trajectories. The scheme is exact and, together with the use of trajectory-based statistical techniques, can be exploited to circumvent the calculation and storage of many-body quantities (e.g., wave function and potential-energy surface) whose size scales exponentially with the number of nuclear degrees of freedom. As a proof of concept, we present numerical simulations of a 2-dimensional model porphine where switching from concerted to sequential double proton transfer (and back) is induced quantum mechanically.

Mechanistic study of the titanocene(III)-catalyzed radical arylation of epoxides.

An atom-economical and catalytic arylation of epoxide-derived radicals is described. The key step of the catalytic system is a sequential electron and proton transfer for the rearomatization of the radical σ-complex and catalyst regeneration. Kinetic, computational, spectroscopic, and cyclovoltammetric investigations highlight the key issues of the reaction mechanism and catalyst stabilization by collidine hydrochloride. Studies employing radicophiles rule out the participation of cations as reactive intermediates.

Asymmetric Transport Mechanisms of Hydronium and Hydroxide Ions in Amorphous Solid Water: Hydroxide Goes Brownian while Hydronium Hops.

The diffusion of hydronium (H3O(+)) and hydroxide (OH(-)) ions is one of the most intriguing topics in aqueous chemistry. It is considered that these ions in aqueous solutions move via sequential proton transfer events, known as the Grotthuss mechanisms. Here, we present an experimental study of the diffusion and H/D exchange of hydronium and hydroxide ions in amorphous solid water (ASW) at 140-180 K by using low-energy sputtering (LES) and temperature-programmed desorption (TPD) measurements. The study shows that the two species transport in ASW via fundamentally different molecular mechanisms. Whereas hydronium ions migrate via efficient proton transfer, hydroxide ions move via Brownian molecular diffusion without proton transfer. The molecular hydroxide diffusion in ASW is in stark contrast to the current view of the hydroxide diffusion mechanism in aqueous solution, which involves proton transfer.

Proton-coupled electron transfer in molecular electrocatalysis: theoretical methods and design principles.

Molecular electrocatalysts play an essential role in a wide range of energy conversion processes. The objective of electrocatalyst design is to maximize the turnover frequency and minimize the overpotential for the overall catalytic cycle. Typically, the catalytic cycle is dominated by key proton-coupled electron transfer (PCET) processes comprised of sequential or concerted electron and proton transfer steps. Theoretical methods have been developed to investigate the mechanisms, thermodynamics, and kinetics of PCET processes in electrocatalytic cycles. Electronic structure methods can be used to calculate the reduction potentials and pKa's and to generate thermodynamic schemes, free energy reaction pathways, and Pourbaix diagrams, which indicate the most stable species under certain conditions. These types of calculations have assisted in identifying the thermodynamically favorable mechanisms under specified experimental conditions, such as acid strength and overpotential. Such calculations have also revealed linear correlations among the thermodynamic properties, which can be used to predict the impact of modifying the ligands, substituents, or metal centers. The thermodynamic properties can be tuned with electron-withdrawing or electron-donating substituents. Ligand modification can exploit the role of noninnocent ligands. For example, ligand protonation typically decreases the overpotential. Calculations of rate constants for electron and proton transfer, as well as concerted PCET, have assisted in identifying the kinetically favorable mechanisms under specified conditions. The concerted PCET mechanism is thought to lower the overpotential required for catalysis by avoiding high-energy intermediates. Rate constant calculations have revealed that the concerted mechanism involving intramolecular proton transfer will be favored by designing more flexible ligands that facilitate the proton donor-acceptor motion while also maintaining a sufficiently short equilibrium proton donor-acceptor distance. Overall, theoretical methods have assisted in the interpretation of experimental data and the design of more effective molecular electrocatalysts.

Intermolecular Proton-Coupled Electron Transfer through H-Bond Complexes in a p-Phenylenediamine-Based Urea Use of the Wedge Scheme to Describe Reactions of this Type

There is a growing appreciation of the important role that H-bond complexes can play in the mechanism of proton-coupled electron transfer (PCET) reactions. Until relatively recently it had been thought that PCET reactions always proceeded step-wise with sequential electron and proton transfer. Much of the recent fundamental interest in PCET stems from the realization that a third option is available, concerted electron and proton transfer or CPET in which the electron and proton both move in a single kinetic step. This interest in the concerted process has increased awareness of H-bonding states in PCET, since the concerted reaction occurs within a H-bonded intermediate. However, even if the proton and electron transfer is not concerted, the H-bonded complex formed in the process of proton transfer can play an important role in the PCET mechanism if it is sufficiently long-lived.Recently we have introduced a generally useful mechanistic framework with which to include H-bonding steps within an overall PCET pathway. This scheme, which for obvious reasons we call a “wedge”, is shown in Scheme 1 for the generic 1e−, 1H+ oxidation, AH + B = A + HB+ + e−. The front face in the wedge (in bold) is the standard electron transfer/proton transfer square scheme, with the two possible electron transfer reactions on the top and bottom edges, and the two possible proton transfers on the left and right edges. However, proton transfer reactions actually go through a H-bond intermediate, so a more accurate description of the proton transfer follows the dashed lines on the triangular sides of the wedge to and from the H-bond intermediates, A-H-B or A-H-B+, which are meant to represent the thermodynamically most stable H-bond complex in each oxidation state. If the H-bonded intermediate has sufficient lifetime, then electron transfer to/from the H-bond complex is also possible, represented by the rear edge of the wedge (thin solid line). If the proton moves from being more attached to A in A-H-B to being more attached to B in A-H-B+, then E° of this reaction is that of the CPET step, if the proton doesn’t move then the E° is simply that of oxidation of the H-bond complex. Either way, it is straightforward to show that E°(A-H-B0/+) has to have a value in between E°(AH0/+) and E°(A−/0). Thus the possibility of electron transfer through the H-bond complex opens up a pathway of intermediate potential for the overall reaction AH + B = A + HB+ + e−.The usefulness of the wedge scheme is demonstrated by its ability to explain the unusual electrochemistry of the phenylenediamine-based urea, U(H)H, which we have shown undergoes a self proton transfer upon oxidation to give half equivalent of the doubly oxidized quinoidal cation and half-equivalent of the electroinactive, protonated reduced urea, Scheme 2. The reaction gives chemically irreversible voltammetry in acetonitrile as would be expected given that the quinoidal cation is harder to reduce than the initially formed radical cation. However, it gives reversible voltammetry in methylene chloride, which can be explained by the greater stability of the H-bonded intermediate in this solvent. In addition, in methylene chloride, we are able to clearly observe a concentration and scan rate dependent conversion between two different reduction pathways on the return scan. This behavior cannot be explained by a simple square scheme, but is readily explained by the wedge scheme.In this presentation, we will report recent results on the voltammetry of U(H)H in the presence of guest molecules that H-bond to the starting, reduced state. We will show that their effect on the voltammetry can be explained in terms of two interlinked wedge schemes, one representing the electron transfer / H-bonding / proton transfer reactions of U(H)H with itself and the other representing the reactions with the added guest.

Proton-Coupled Electron Transfer with Photoexcited Metal Complexes

Proton-coupled electron transfer (PCET) plays a crucial role in many enzymatic reactions and is relevant for a variety of processes including water oxidation, nitrogen fixation, and carbon dioxide reduction. Much of the research on PCET has focused on transfers between molecules in their electronic ground states, but increasingly researchers are investigating PCET between photoexcited reactants. This Account describes recent studies of excited-state PCET with d(6) metal complexes emphasizing work performed in my laboratory. Upon photoexcitation, some complexes release an electron and a proton to benzoquinone reaction partners. Others act as combined electron-proton acceptors in the presence of phenols. As a result, we can investigate photoinduced PCET involving electron and proton transfer in a given direction, a process that resembles hydrogen-atom transfer (HAT). In other studies, the photoexcited metal complexes merely serve as electron donors or electron acceptors because the proton donating and accepting sites are located on other parts of the molecular PCET ensemble. We and others have used this multisite design to explore so-called bidirectional PCET which occurs in many enzymes. A central question in all of these studies is whether concerted proton-electron transfer (CPET) can compete kinetically with sequential electron and proton transfer steps. Short laser pulses can trigger excited-state PCET, making it possible to investigate rapid reactions. Luminescence spectroscopy is a convenient tool for monitoring PCET, but unambiguous identification of reaction products can require a combination of luminescence spectroscopy and transient absorption spectroscopy. Nevertheless, in some cases, distinguishing between PCET photoproducts and reaction products formed by simple photoinduced electron transfer (ET) (reactions that don't include proton transfer) is tricky. Some of the studies presented here deal directly with this important problem. In one case study we employed a cyclometalated iridium(III) complex. Our other studies with ruthenium(II) complexes and phenols focused on systematic variations of the reaction free energies for the CPET, ET, and proton transfer (PT) steps to explore their influence on the overall PCET reaction. Still other work with rhenium(I) complexes concentrated on the question of how the electronic structure of the metal-to-ligand charge transfer (MLCT) excited states affects PCET. We used covalent rhenium(I)-phenol dyads to explore the influence of the electron donor-electron acceptor distance on bidirectional PCET. In covalent triarylamine-Ru(bpy)₃²⁺/Os(bpy)₃²⁺-anthraquinone triads (bpy = 2,2'-bipyridine), hydrogen-bond donating solvents significantly lengthened the lifetimes of photogenerated electron/hole pairs because of hydrogen-bonding to the quinone radical anion. Until now, comparatively few researchers have investigated this variation of PCET: the strengthening of H-bonds upon photoreduction.

Concerted and Sequential Proton Transfer Mechanisms in Water-Separated Acid–Base Encounter Pairs

The proton transfer mechanisms involved inside aqueous, solvent-separated encounter complexes between phenol and carboxyl moieties are studied using ab initio molecular dynamics and computational time-resolved vibrational spectroscopy. This model framework can be viewed as a ground-state analog of the excited-state proton transfer reactions that have been actively investigated using ultrafast spectroscopy. Three qualitatively distinct proton transfer pathways are observed in the simulations. These can be described as direct concerted, direct sequential, and through bulk transfers. The primary difference between the sequential and concerted mechanism is the involvement of a reaction intermediate in which the proton fluctuates for several picoseconds through the hydrogen bonds connecting donor and acceptor but resides primarily on an intervening water molecule in the encounter complex. These results contribute to our molecular level understanding of the diverse processes involved in proton transfer within water-separated encounter complexes.

Catalytic Mechanism of 4-Oxalocrotonate Tautomerase: Significances of Protein–Protein Interactions on Proton Transfer Pathways

4-Oxalocrotonate tautomerase (4-OT), a member of tautomerase superfamily, is an essential enzyme in the degradative metabolism pathway occurring in the Krebs cycle. The proton transfer process catalyzed by 4-OT has been explored previously using both experimental and theoretical methods; however, the elaborate catalytic mechanism of 4-OT still remains unsettled. By combining classical molecular mechanics with quantum mechanics, our results demonstrate that the native hexametric 4-OT enzyme, including six protein monomers, must be employed to simulate the proton transfer process in 4-OT due to protein-protein steric and electrostatic interactions. As a consequence, only three out of the six active sites in the 4-OT hexamer are observed to be occupied by three 2-oxo-4-hexenedioates (2o4hex), i.e., half-of-the-sites occupation. This agrees with experimental observations on negative cooperative effect between two adjacent substrates. Two sequential proton transfers occur: one proton from the C3 position of 2o4hex is initially transferred to the nitrogen atom of the general base, Pro1. Subsequently, the same proton is shuttled back to the position C5 of 2o4hex to complete the proton transfer process in 4-OT. During the catalytic reaction, conformational changes (i.e., 1-carboxyl group rotation) of 2o4hex may occur in the 4-OT dimer model but cannot proceed in the hexametric structure. We further explained that the docking process of 2o4hex can influence the specific reactant conformations and an alternative substrate (2-hydroxymuconate) may serve as reactant under a different reaction mechanism than 2o4hex.

Charge transport in poly-imidazole membranes: a fresh appraisal of the Grotthuss mechanism

A detailed theoretical investigation of the charge transport mechanism in poly(4-vinyl-imidazole) (P4VI), the parent polymer of a series of N-heterocyclic-based membranes used as an electrolyte in proton exchange membrane fuel cells, is presented. In particular, Density Functional Theory (DFT) results obtained for small model systems (protonated imidazole dimers and trimers) suggest that the commonly accepted conduction mechanism, based on a sequential proton transfer between imidazole moieties, could be impeded by the geometrical constraints imposed by the polymeric backbone. Indeed only one kind of proton transfer reaction is energetically allowed between adjacent imidazoles, so that a rotation of the protonated imidazole is required for a second proton transfer. Molecular dynamics simulations on a larger model (15 oligomers with an excess proton) show that the rotation of the imidazole carrying the excess proton is a soft large amplitude motion. These results allow us to propose a new proton conduction mechanism in P4VI, where a frustrated rotation of the protonated imidazole before each proton transfer reaction represents the rate-limiting step. Furthermore, in contrast with the Grotthuss proton transport mechanism in water, our results indicate that here it is the same proton which could be successively transferred. From a chemical point of view, these new insights into the mechanism are relevant for a rational design of modified azole-based systems for Proton Exchange Membrane Fuel Cells.

Studies on electron transfer reactions: oxidation of phenol and ring-substituted phenols by heteropoly 11-tungstophosphovanadate(V) in aqueous acidic medium

The kinetics of oxidation of phenol and a few ring-substituted phenols by heteropoly 11-tungstophosphovanadate(V), [PVVW11O40]4− (HPA) have been studied spectrophotometrically in aqueous acidic medium containing perchloric acid and also in acetate buffers of several pH values at 25 °C. EPR and optical studies show that HPA is reduced to the one-electron reduced heteropoly blue (HPB) [PVIVW11O40]5−. In acetate buffers, the build up and decay of the intermediate biphenoquinone show the generation of phenoxyl radical (ArO·) in the rate-determining step. At constant pH, the reaction shows simple second-order kinetics with first-order dependence of rate on both [ArOH] and [HPA]. At constant [ArOH], the rate of the reaction increases with increase in pH. The plot of apparent second-order rate constant, k 2, versus 1/[H+] is linear with finite intercept. This shows that both the undissociated phenol (ArOH) and the phenoxide ion (ArO−) are the reactive species. The ArO−–HPA reaction is the dominant pathway in acetate buffer and it proceeds through the OH− ion triggered sequential proton transfer followed by electron transfer (PT-ET) mechanism. The rate constant for ArO−–HPA reaction, calculated using Marcus theory, agrees fairly well with the experimental value. The reactivity of substituted phenoxide ions correlates with the Hammett σ+ constants, and ρ value was found to be −4.8. In acidic medium, ArOH is the reactive species. Retardation of rate for the oxidation of C6H5OD in D2O indicates breaking of the O–H bond in the rate-limiting step. The results of kinetic studies show that the HPA-ArOH reaction proceeds through a concerted proton-coupled electron transfer mechanism in which water acts as proton acceptor (separated-CPET).

Iridium-Catalyzed Hydrogenation of N-Heterocyclic Compounds under Mild Conditions by an Outer-Sphere Pathway

A new homogeneous iridium catalyst gives hydrogenation of quinolines under unprecedentedly mild conditions-as low as 1 atm of H(2) and 25 °C. We report air- and moisture-stable iridium(I) NHC catalyst precursors that are active for reduction of a wide variety of quinolines having functionalities at the 2-, 6-, and 8- positions. A combined experimental and theoretical study has elucidated the mechanism of this reaction. DFT studies on a model Ir complex show that a conventional inner-sphere mechanism is disfavored relative to an unusual stepwise outer-sphere mechanism involving sequential proton and hydride transfer. All intermediates in this proposed mechanism have been isolated or spectroscopically characterized, including two new iridium(III) hydrides and a notable cationic iridium(III) dihydrogen dihydride complex. DFT calculations on full systems establish the coordination geometry of these iridium hydrides, while stoichiometric and catalytic experiments with the isolated complexes provide evidence for the mechanistic proposal. The proposed mechanism explains why the catalytic reaction is slower for unhindered substrates and why small changes in the ligand set drastically alter catalyst activity.

A Twin-track Approach Has Optimized Proton and Hydride Transfer by Dynamically Coupled Tunneling during the Evolution of Protochlorophyllide Oxidoreductase

Protein dynamics are crucial for realizing the catalytic power of enzymes, but how enzymes have evolved to achieve catalysis is unknown. The light-activated enzyme protochlorophyllide oxidoreductase (POR) catalyzes sequential hydride and proton transfers in the photoexcited and ground states, respectively, and is an excellent system for relating the effects of motions to catalysis. Here, we have used the temperature dependence of isotope effects and solvent viscosity measurements to analyze the dynamics coupled to the hydride and proton transfer steps in three cyanobacterial PORs and a related plant enzyme. We have related the dynamic profiles of each enzyme to their evolutionary origin. Motions coupled to light-driven hydride transfer are conserved across all POR enzymes, but those linked to thermally activated proton transfer are variable. Cyanobacterial PORs require complex and solvent-coupled dynamic networks to optimize the proton donor-acceptor distance, but evolutionary pressures appear to have minimized such networks in plant PORs. POR from Gloeobacter violaceus has features of both the cyanobacterial and plant enzymes, suggesting that the dynamic properties have been optimized during the evolution of POR. We infer that the differing trajectories in optimizing a catalytic structure are related to the stringency of the chemistry catalyzed and define a functional adaptation in which active site chemistry is protected from the dynamic effects of distal mutations that might otherwise impact negatively on enzyme catalysis.