Antibody-catalyzed benzoin oxidation as a mechanistic probe for nucleophilic catalysis by an active site lysine

Aldolase antibody 24H6, which was obtained by reactive immunization against a 1,3-diketone hapten, is shown to catalyze additional reactions, including H/D exchange and oxidation reactions. Comparison of the H/D exchange reaction at the alpha-position of a wide range of aldehydes and ketones by 24H6 and by other aldolase antibodies, such as 38C2, pointed at the significantly larger size of the 24H6 active site. This property allowed for the catalysis of the oxidation of substituted benzoins to benzils by potassium ferricyanide. This reaction was used as a mechanistic probe to learn about the initial steps of the 24H6-catalyzed aldol condensation reaction. The Hammett correlation (rho=4.7) of log(k(cat)) versus the substituent constant, sigma, revealed that the reaction involves rapid formation of a Schiff base intermediate from the ketone and an active site lysine residue. The rate-limiting step in this oxidation reaction is the conversion of the Schiff base to an enamine intermediate. In addition, linear correlation (rho=3.13) was found between log(K(M)) and sigma, indicating that electronic rather than steric factors are dominant in the antibody-substrate binding phenomenon and confirming that the reversible formation of a Schiff base intermediate comprises part of the substrate-binding mechanism.     

D-Fructose-6-phosphate aldolase-catalyzed one-pot synthesis of iminocyclitols

A one-pot chemoenzymatic method for the synthesis of a variety of new iminocyclitols from readily available, non-phosphorylated donor substrates has been developed. The method utilizes the recently discovered fructose-6-phosphate aldolase (FSA), which is functionally distinct from known aldolases in its tolerance of different donor substrates as well as acceptor substrates. Kinetic studies were performed with dihydroxyacetone (DHA), the presumed endogenous substrate for FSA, as well as hydroxy acetone (HA) and 1-hydroxy-2-butanone (HB) as donor substrates, in each case using glyceraldehyde-3-phosphate as acceptor substrate. Remarkably, FSA used the three donor substrates with equal efficiency, with kcat/KMvalues of 33, 75, and 20 M-1 s-1, respectively. This level of donor substrate tolerance is unprecedented for an aldolase. Furthermore, DHA, HA, and HB were accepted as donors in FSA-catalyzed aldol reactions with a variety of azido- and Cbz-amino aldehyde acceptors. The broad substrate tolerance of FSA and the ability to circumvent the need for phosphorylated substrates allowed for one-pot synthesis of a number of known and novel iminocyclitols in good yields, and in a very concise fashion. New iminocyclitols were assayed as inhibitors against a panel of glycosidases. Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and selective inhibitors of beta-N-acetylglucosaminidases in the submicromolar range. Facile access to these compounds makes them attractive core structures for further inhibitor optimization.     

Catalytic asymmetric aldol reactions in aqueous media

Nature has perfected the stereospecific aldol reaction by using aldolase enzymes. While virtually all the biochemical aldol reactions use unmodified donor and acceptor carbonyls and take place under catalytic control in an aqueous environment, the chemical domain of the aldol addition has mostly relied on prior transformation of carbonyl substrates, and the whole process traditionally is carried out in anhydrous solvents. The area of aqua-asymmetric aldol reactions has received much attention recently in light of the perception both of its green chemistry advantages and its analogy to eon-perfected enzyme catalysis. Both chiral metal complexes and small chiral organic molecules have been recently reported to catalyze aldol reactions with relatively high chemical and stereochemical efficiency. This tutorial review describes recent developments in this area.     

Antibody-catalyzed removal of the p-nitrobenzyl ester protecting group: the molecular basis of broad substrate specificity

Antibody catalysts for the removal of the p-nitrobenzyl ester protecting group have been generated to accommodate a broad range of substrates. Antibody 7B9, which was elicited against p-nitrobenzyl phosphonate 1, catalyzed the hydrolyses of p-nitrobenzyl monoesters of nonsubstituted, and beta- and gamma-substituted glutaric acids with almost identical Km and kcat values. In addition, 7B9 displayed substrate tolerance towards the a-substituents and accepted the p-nitrobenzyl esters of Leu, Norleu, and Phe. To define the molecular basis of the broad substrate tolerance, we have cloned and sequenced the antibody and constructed a model of the active-site-hapten complex. The model showed a relatively shallow pocket of the antigen-combining site that accommodates the p-nitrobenzyl moiety, and this is consistent with the observed substrate specificity. Thus, in the antibody-catalyzed reaction, the alpha-, beta-, and gamma-substituents of the substrates should be outside the combining site and ignored by the antibody recognition. A structural comparison of 7B9 with antibody D2.3, elicited against the structurally similar haptenic phosphonate, suggests the significance of the linker moiety in hapten design, which endows antibody catalysts with broad substrate specificity. These investigations provide new strategies for the generation of catalytic antibodies that accept a broad range of substrates for practical applications in organic synthetic chemistry.     

Metal ion promoted transesterifications of carboxylate esters. A structure/activity study of the efficacy of Zn2+ and La3+ to catalyze the methanolysis of some aryl and aliphatic esters

The methanolysis of various aryl and aliphatic carboxylate esters promoted by methoxide, 1,5,9-triazacyclododecane : Zn2+(-OCH3) and La3+(-OCH3), were studied and the derived rate constants (kOCH3, kcat3:Zn(OCH3) and kcatLa(OCH3)) correlated in various ways. The metal ion catalyzed reactions are very much faster than the background reactions in some cases reaching up to 7 x 10(6)-fold acceleration when present at concentrations of 5 mmol dm(-3). The data for both metals exhibit non-linear Bronsted correlations with the pKa of the leaving group which are analyzed in terms of a change in rate limiting step from formation to breakdown of a metal-coordinated tetrahedral intermediate as the pKa increases above values of approximately 14.7. Plots of the log kOCH3 reaction vs. the log kcat values for each metal ion indicate low sensitivity for aryl esters and a higher sensitivity for the aliphatic esters. A mechanistic rationale for the observations is presented.     

Water-catalyzed gas-phase hydrogen abstraction reactions of CH3O2 and HO2 with HO2: a computational investigation

The gas-phase hydrogen abstraction reactions of CH(3)O(2) and HO(2) with HO(2) in the presence and absence of a single water molecule have been studied at the CCSD(T)/6-311++G(3d,2p)//B3LYP/6-311G(2d,2p) level of theory. The calculated results show that the process for O(3) formation is much faster than that for (1)O(2) and (3)O(2) formation in the water-catalyzed CH(3)O(2) + HO(2) reaction. This is different from the results for the non-catalytic reaction of CH(3)O(2) + HO(2), in which almost only the process for (3)O(2) formation takes place. Unlike CH(3)O(2) + HO(2) reaction in which the preferred process is different in the catalytic and non-catalytic conditions, the channel for (3)O(2) formation is the dominant in both catalytic and non-catalytic HO(2) + HO(2) reactions. Furthermore, the calculated total CVT/SCT rate constants for water-catalyzed and non-catalytic title reactions show that the water molecule doesn't contribute to the rate of CH(3)O(2) + HO(2) reaction though the channel for O(3) formation in this water-catalyzed reaction is more kinetically favorable than its non-catalytic process. Meanwhile, the water molecule plays an important positive role in increasing the rate of HO(2) + HO(2) reaction. These results are in good agreement with available experiments.     

Presteady-state kinetic evidence for a ring-opening activity in fructose-1,6-(bis)phosphate aldolase

Fructose 1,6-bisphosphate aldolase, a glycolytic enzyme, catalyzes the cleavage of fructose 1,6-bisphosphate, resulting in two three-carbon products. The reaction of the class I enzymes, which utilize a Schiff-base intermediate, requires that the hexose be in the open-chain form. This form comprises only 1-2% of the sugar at equilibrium. The chemical form of the substrate that binds to aldolase and begins the catalytic cycle has not been unequivocally demonstrated. Transient-state kinetics in single-turnover experiments of fructose 1,6-bisphosphate with aldolase in excess reveals the rates of the intermediate steps in the cleavage reaction, including those from initial binding to Schiff-base formation. The rate of hexose Schiff-base formation was faster than the uncatalyzed rate for ring-opening of either the alpha- or beta-furanose at 4 degrees C. In addition, approach-to-equilibrium experiments reveal that aldolase binds and reacts first with 70% of fructose-1,6-bisphosphate in a fast reaction, consistent with the amount of beta-anomer in solution, and with the remaining 30%, presumably the alpha-anomer, in a slow reaction. These results indicate that aldolase must catalyze the ring-opening step and that there may be a previously unrecognized second active site on the enzyme for catalyzing this reaction.     

In-source H/D exchange and ion-molecule reactions using matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry with pulsed collision and reaction gases

Controlled in-source ion-molecule reactions are performed for the first time in an external matrix assisted laser desorption ionization (MALDI) source of a Fourier transform ion cyclotron resonance mass spectrometer. The MALDI source with a hexapole ion guide that was originally designed to incorporate pulsed gas to collisionally cool ions (Baykut, G.; Jertz, R.; Witt, M. Rapid Commun. Mass Spectrom. 2000, 14, 1238-1247) has been modified to allow the study of in-source ion-molecule reactions. Upon laser desorption, a reaction gas was introduced through a second inlet and allowed to interact with the MALDI-generated ions trapped in the hexapole ion guide. Performing ion-molecule reactions in the high pressure range of the ion source prior to analysis in the ion cyclotron resonance (ICR) cell allows to maintain the ultra high vacuum in the cell which is crucial for high mass resolution measurements. In addition, due to the reaction gas pressure in the hexapole product ion formation is much faster than would be otherwise possible in the ICR cell. H/D exchange reactions with different peptides are investigated, as are proton-bound complex formations. A typical experimental sequence would be ion accumulation in the hexapole ion guide from multiple laser shots, addition of cooling gas during ion formation, addition of reaction gas, varied time delays for the ion-molecule reactions, and transmission of the product ions into the ICR cell for mass analysis. In this MALDI source H/D exchange reactions for different protonated peptides are investigated, as well as proton-bound complex formations with the reaction gas triethylamine. Amino acid sequence, structural flexibility and folding state of the peptides can be seen to play a part in the reactivity of such ions.     

Kinetics and Equilibria of the Thiol/Disulfide Exchange Reactions of Somatostatin with Glutathione

Rate and equilibrium constants are reported for the thiol/disulfide exchange reactions of the peptide hormone somatostatin with glutathione (GSH). GSH reacts with the disulfide bond of somatostatin to form somatostatin-glutathione mixed disulfides (Cys(3)-SH, Cys(14)-SSG and Cys(3)-SSG, Cys(14)-SH), each of which can react with another molecule of GSH to give the reduced dithiol form of somatostatin and GSSG. The mixed disulfides also can undergo intramolecular thiol/disulfide exchange reactions to re-form the disulfide bond of somatostatin or to interconvert to the other mixed disulfide. Analysis of the forward and reverse rate constants indicates that, at physiological concentrations of GSH, the intramolecular thiol/disulfide exchange reactions that re-form the disulfide bond of somatostatin are much faster than reaction of the mixed disulfides with another molecule of GSH, even though the intramolecular reaction involves closure of a 38-membered ring. Thus, even though the disulfide bond of somatostatin is readily cleaved by thiol/disulfide exchange, it is rapidly reformed by intramolecular thiol/disulfide exchange reactions of the somatostatin-glutathione mixed disulfides. By comparison with rate constants reported for analogous reactions of model peptides measured under random coil conditions, it is concluded that disulfide bond formation by intramolecular thiol/disulfide exchange in the somatostatin-glutathione mixed disulfides is not completely random, but rather it is directed to some extent by conformational properties of the mixed disulfides that place the thiol and mixed disulfide groups in close proximity. A reduction potential of -0.221 V was calculated for the disulfide bond of somatostatin from the thiol/disulfide exchange equilibrium constant.     

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1)

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).     

Aldol additions of dihydroxyacetone phosphate to N-Cbz-amino aldehydes catalyzed by L-fuculose-1-phosphate aldolase in emulsion systems: inversion of stereoselectivity as a function of the acceptor aldehyde

The potential of L-fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N-protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100 mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N-protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)-N-Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N-Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N-Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N-Cbz-glycinal and N-Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after C-C bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results.     

Byproduct‐Catalyzed Four‐Component Reactions of Aldehydes with Hexamethyldisilazane,Chloroformates, and Nucleophiles in Acetonitrile Leading to Protected Primary Amines, β‐Amino Esters,and β‐Amino Ketones

Multicomponent reactions are a very powerful tool for the construction of complex organic molecules by using readily available starting materials. While most of the multicomponent reactions discovered so far consist of three components, the reactions with four or more components remain sparse. We have successfully developed several four‐component reactions using a catalytic amount of water as a hydrolyzing agent to decompose byproduct chlorotrimethylsilane (TMSCl) to yield secondary byproduct HCl that serves as a catalyst. In the presence of 40 mol % of water, the four‐component reaction of aldehydes with hexamethyldisilazane (HMDS), chloroformates, and silylated nucleophiles proceeds smoothly at room temperature to give a range of protected primary amines in moderate to excellent yields. Importantly, a wide variety of protic carbon nucleophiles, such as β‐keto esters, β‐diketones, and ketones, have further been explored as suitable substrates for the synthesis of protected β‐amino esters and β‐amino ketones that are useful building blocks for various pharmaceuticals and natural products. These four‐component reactions proceed through a pathway of tandem nitrogen protection/imine formation/imine addition, and the decomposition of byproduct TMSCl, generated in the first step of nitrogen protection, with water results in the formation of secondary byproduct HCl, a strong Brønsted acid that catalyzes the following imine formation/imine addition. Taking advantage of the fact that alcohols or phenols are also able to decompose byproduct TMSCl to yield secondary byproduct HCl, no catalyst is needed at all for the four‐component reactions with aldehydes bearing hydroxy groups.     

Macromolecular salen catalyst with largely enhanced catalytic activity

A dinuclear copper(II) Schiff-base complex was immobilized in a poly(acrylate) matrix by emulsion polymerization. The spheric microbeads were used for aerobic catalytic oxidation of 3,5-di-tert-butylcatechol into 3,5-di-tert-butylquinone in methanol at ambient temperature to study the contribution of the macromolecular matrix to the overall rate acceleration of the reaction. The polymeric catalyst catalyzes the oxidation about 1 order of magnitude faster (kcat/knon = 470,000) than its low molecular weight analogue (kcat/knon = 60,000).     

A simple DNase model system comprising a dinuclear Zn(II) complex in methanol accelerates the cleavage of a series of methyl aryl phosphate diesters by 10(11)-10(13)

The di-Zn(II) complex of 1,3-bis[ N1, N1'-(1,5,9-triazacyclododecyl)]propane with an associated methoxide ( 3:Zn(II) 2: (-)OCH 3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters ( 6) was studied at s (s)pH 9.8 in methanol at 25.0 +/- 0.1 degrees C. Plots of k obs vs [ 3:Zn(II) 2: (-)OCH 3] free for all members of 6 show saturation behavior from which K(M) and kcat (max) were determined. The second order rate constants for the catalyzed reactions (kcat (max)/K(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k 2 (-OMe)) by 1.4 x 10(8) to 3 x 10 (9)-fold. The values of k cat (max) for all members of 6 are between 4 x 10(11) and 3 x 10(13) times larger than the solution reaction at s (s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO 2 or C(O)OCH 3 groups. Based on the linear Br?nsted plots of k cat (max) vs s (s)pKa of the phenol, beta lg values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO 2 or C(O)OCH 3 groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH 3O (-): 6], giving a hypothetical [ 3:Zn(II) 2:CH 3O (-): 6] complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO 2 or C(O)OCH 3 groups.     

Unusual reversal of regioselectivity in antibody-mediated aldol additions with unsymmetrical methyl ketones

A catalytic regio- and enantioselective aldol reaction of various unsymmetrical methyl ketones with para-nitrobenzaldehyde has been developed using aldolase antibodies as the catalysts. It has been found that the sense and level of regioselectivity for the reactions catalysed by antibody 38C2 and 33F12 are highly dependent on the structure of both the donor and the acceptor but in contrast, antibodies 84G3 and 93F3 catalyse the exclusive formation of the linear regioisomer independent of the structure of the reactants examined. The level of enantiocontrol is very high for most reactions. Both linear aldol enantiomers could be accessed through aldol or retro-aldol reactions using the same antibody. Theoretical studies on regioisomeric α- and β-heteroatom substituted enamines derived from unsymmetrical ketones suggest that most of the linear aldol products formed in the presence of antibodies 84G3 and 93F3 must be formed from intermediate enamines which are not the thermodynamically most favourable.     

Mechanistic study of protein phosphatase-1 (PP1), a catalytically promiscuous enzyme

The reaction catalyzed by the protein phosphatase-1 (PP1) has been examined by linear free energy relationships and kinetic isotope effects. With the substrate 4-nitrophenyl phosphate (4NPP), the reaction exhibits a bell-shaped pH-rate profile for kcat/KM indicative of catalysis by both acidic and basic residues, with kinetic pKa values of 6.0 and 7.2. The enzymatic hydrolysis of a series of aryl monoester substrates yields a Br?nsted beta(lg) of -0.32, considerably less negative than that of the uncatalyzed hydrolysis of monoester dianions (-1.23). Kinetic isotope effects in the leaving group with the substrate 4NPP are (18)(V/K) bridge = 1.0170 and (15)(V/K) = 1.0010, which, compared against other enzymatic KIEs with and without general acid catalysis, are consistent with a loose transition state with partial neutralization of the leaving group. PP1 also efficiently catalyzes the hydrolysis of 4-nitrophenyl methylphosphonate (4NPMP). The enzymatic hydrolysis of a series of aryl methylphosphonate substrates yields a Br?nsted beta(lg) of -0.30, smaller than the alkaline hydrolysis (-0.69) and similar to the beta(lg) measured for monoester substrates, indicative of similar transition states. The KIEs and the beta(lg) data point to a transition state for the alkaline hydrolysis of 4NPMP that is similar to that of diesters with the same leaving group. For the enzymatic reaction of 4NPMP, the KIEs are indicative of a transition state that is somewhat looser than the alkaline hydrolysis reaction and similar to the PP1-catalyzed monoester reaction. The data cumulatively point to enzymatic transition states for aryl phosphate monoester and aryl methylphosphonate hydrolysis reactions that are much more similar to one another than the nonenzymatic hydrolysis reactions of the two substrates.     

Mechanism of radiation-induced addition reaction of carbon tetrachloride onto liquid 1,2-polybutadiene accompanied by cyclization

Effects of irradiation conditions were investigated in the γ-ray-induced addition reaction of carbon tetrachloride onto liquid 1,2-polybutadiene. The rate of addition reaction was proportional to the dose rate, and its apparent activation energy was 1.4 kcal/mole in the range of ca. 20–80°C; the G values for the addition of carbon tetrachloride and vinyl consumption were high. The addition reactions of methyl isobutylate, isopropyl amine, and bromotrichloromethane to liquid 1,2-polybutadiene by γ rays were studied to compare with carbon tetrachloride. Methyl isobutylate and isopropyl amine were added much more slowly. On the other hand, in bromotrichloromethane the rate of addition reaction was much faster but cyclization was less pronounced than in carbon tetrachloride. On the basis of these results a mechanism of a radical chain reaction which includes the addition of carbon tetrachloride, cyclization, and crosslinking, is proposed.     

On-demand generation of an efficient catalyst for pyridine formation from unactivated nitriles and alpha,omega-diynes using CoCl2-6H2O, dppe, and Zn

[reaction: see text] A highly practical, general method for catalytic formation of substituted pyridines from a variety of unactivated nitriles and alpha,omega-diynes is given. The reactions which were catalyzed by 5 mol % of dppe/CoCl2-6H2O in the presence of Zn powder (10 mol %) could proceed at rt to approximately 50 degrees C with high functional compatibility and regioselectivity.     

Contrasting reactions of ketones and thioketones with alkyllithiums: a coordinated experimental and computational investigation

The reaction of ketones with organolithium reagents generally proceeds by addition of the organometallic to the electrophilic carbon of the C═O group to give the lithium salt of a tertiary alcohol. The seemingly analogous reaction of thioketones with organolithiums is a fundamentally different process: such reactions typically afford a variety of products, and addition of the organolithium to carbon of the C═S group to give a thiol is a relatively unimportant component. Reactions of the stable thioketone, adamantantanethione (1), with several alkyllithiums (MeLi, n-BuLi and t-BuLi) in a variety of solvents have been studied in the first comprehensive investigation of the reactions of organolithiums with a representative alkyl-substituted thione. Reactions of 1 with n-BuLi or t-BuLi afforded 2-adamantanethiol (2) as the major product. In an effort to explain the marked difference in behavior of ketones and thioketones in reactions with organolithiums, transition states for both the addition and reduction reactions have been located at the B3LYP/6-311+G* level using acetone and thioacetone as model substrates. The transition states for the addition of dimeric MeLi to the C═O and C═S carbons of acetone and thioacetone were significantly different as a result of the small bond angles preferred by divalent sulfur, and this accounts for the much slower addition to a C═S carbon vis-à-vis a C═O group. Transition states for reduction of acetone and thioacetone by EtLi were similar, but the greater exothermicity of the reduction of the thioketone results in an earlier transition state and lower activation energy for this process than that for the reduction of a ketone. The possible role of radical-mediated processes in this chemistry is also discussed.     

Catalytic water formation on platinum: a first-principles study.

The study of catalytic behavior begins with one seemingly simple process, namely the hydrogenation of O to H2O on platinum. Despite the apparent simplicity its mechanism has been much debated. We have used density functional theory with gradient corrections to examine microscopic reaction pathways for several elementary steps implicated in this fundamental catalytic process. We find that H2O formation from chemisorbed O and H atoms is a highly activated process. The largest barrier along this route, with a value of approximately 1 eV, is the addition of the first H to O to produce OH. Once formed, however, OH groups are easily hydrogenated to H2O with a barrier of approximately 0.2 eV. Disproportionation reactions with 1:1 and 2:1 stoichiometries of H2O and O have been examined as alternative routes for OH formation. Both stoichiometries of reaction produce OH groups with barriers that are much lower than that associated with the O + H reaction. H2O, therefore, acts as an autocatalyst in the overall H2O formation process. Disproportionation with a 2:1 stoichiometry is thermodynamically and kinetically favored over disproportionation with a 1:1 stoichiometry. This highlights an additional (promotional) role of the second H2O molecule in this process. In support of our previous suggestion that the key intermediate in the low-temperature H2O formation reaction is a mixed OH and H2O overlayer we find that there is a very large barrier for the dissociation of the second H2O molecule in the 2:1 disproportionation process. We suggest that the proposed intermediate is then hydrogenated to H2O through a very facile proton-transfer mechanism.