Showing papers on "Transition state published in 2003"

Kinetic and stereochemical evidence for the involvement of only one proline molecule in the transition states of proline-catalyzed intra- and intermolecular aldol reactions.

Abstract: Contrary to the widely accepted mechanism of the Hajos−Parrish−Eder−Sauer−Wiechert reaction, we have obtained evidence for the involvement of only one proline molecule in the transition states of both inter- and intramolecular aldol reactions. Our conclusions are based on kinetic measurements and the absence of nonlinear and dilution effects on the asymmetric catalysis, and are supported by B3LYP/6-31G* calculations. Complementary to recent theoretical studies, our results provide the foundation of a unified enamine catalysis mechanism of proline-catalyzed inter- and intramolecular aldol reactions.

Exploring potential energy surfaces for chemical reactions: An overview of some practical methods

Abstract: Potential energy surfaces form a central concept in the application of electronic structure methods to the study of molecular structures, properties, and reactivities. Recent advances in tools for exploring potential energy surfaces are surveyed. Methods for geometry optimization of equilibrium structures, searching for transition states, following reaction paths and ab initio molecular dynamics are discussed. For geometry optimization, topics include methods for large molecules, QM/MM calculations, and simultaneous optimization of the wave function and the geometry. Path optimization methods and dynamics based techniques for transition state searching and reaction path following are outlined. Developments in the calculation of ab initio classical trajectories in the Born-Oppenheimer and Car-Parrinello approaches are described.

Control of ethylene epoxidation selectivity by surface oxametallacycles.

Abstract: Surface science experiments, DFT calculations, and kinetic isotope effect data are utilized to understand the elementary steps that govern the selectivity of silver catalysts for the partial oxidation of ethylene to produce ethylene oxide. It is proposed that selective and unselective pathways proceed via a common intermediate, the surface oxametallacycle. The structures of the transition states leading from this intermediate to selective and unselective products are calculated. From the calculated Gibbs free energies of activation for competing pathways, it is possible to predict selectivity to ethylene oxide as well as the magnitude of the kinetic isotope effect. The proposed mechanism is qualitatively and quantitatively in accord with experimental results.

Mapping the conformational itinerary of β-glycosidases by X-ray crystallography

Abstract: The conformational agenda harnessed by different glycosidases along the reaction pathway has been mapped by X-ray crystallography. The transition state(s) formed during the enzymic hydrolysis of glycosides features strong oxocarbenium-ion-like character involving delocalization across the C-1-O-5 bond. This demands planarity of C-5, O-5, C-1 and C-2 at or near the transition state. It is widely, but incorrectly, assumed that the transition state must be (4)H(3) (half-chair). The transition-state geometry is equally well supported, for pyranosides, by both the (4)H(3) and (3)H(4) half-chair and (2,5)B and B(2,5) boat conformations. A number of retaining beta-glycosidases acting on gluco -configured substrates have been trapped in Michaelis and covalent intermediate complexes in (1)S(3) (skew-boat) and (4)C(1) (chair) conformations, respectively, pointing to a (4)H(3)-conformed transition state. Such a (4)H(3) conformation is consistent with the tight binding of (4)E- (envelope) and (4)H(3)-conformed transition-state mimics to these enzymes and with the solution structures of compounds bearing an sp (2) hybridized anomeric centre. Recent work reveals a (1)S(5) Michaelis complex for beta-mannanases which, together with the (0)S(2) covalent intermediate, strongly implicates a B(2,5) transition state for beta-mannanases, again consistent with the solution structures of manno -configured compounds bearing an sp (2) anomeric centre. Other enzymes may use different strategies. Xylanases in family GH-11 reveal a covalent intermediate structure in a (2,5)B conformation which would also suggest a similarly shaped transition state, while (2)S(0)-conformed substrate mimics spanning the active centre of inverting cellulases from family GH-6 may also be indicative of a (2,5)B transition-state conformation. Work in other laboratories on both retaining and inverting alpha-mannosidases also suggests non-(4)H(3) transition states for these medically important enzymes. Three-dimensional structures of enzyme complexes should now be able to drive the design of transition-state mimics that are specific for given enzymes, as opposed to being generic or merely fortuitous.

Dynamics-Driven Reaction Pathway in an Intramolecular Rearrangement

Abstract: A critical role is traditionally assigned to transition states (TSs) and minimum energy pathways, or intrinsic reaction coordinates (IRCs), in interpreting organic reactivity. Such an interpretation, however, ignores vibrational and kinetic energy effects of finite temperature. Recently it has been shown that reactions do not necessarily follow the intermediates along the IRC. We report here molecular dynamics (MD) simulations that show that dynamics effects may alter chemical reactions even more. In the heterolysis rearrangement of protonated pinacolyl alcohol Me3C-CHMe-OH2+ (Me, methyl), the MD pathway involves a stepwise route with C-O bond cleavage followed by methyl group migration, whereas the IRC pathway suggests a concerted mechanism. Dynamics effects may lead to new interpretations of organic reactivity.

Spectroscopic and theoretical studies of CH+ 3-Rgn clusters (Rg=He, Ne, Ar): From weak intermolecular forces to chemical reaction mechanisms

Abstract: This review summarizes the recent combined experimental and theoretical effort of high-resolution spectroscopy, mass spectrometry and quantum chemical calculations to characterize isolated CH+ 3-Rg n clusters (Rg=He, Ne, Ar; n ≤ 8). These complexes serve as a model system for the solvation of a fundamental reactive carbocation by non-polar ligands. The results provide unprecedented and detailed information about important properties of the interaction potential as a function of the interaction strength and the degree of microsolvation of the methyl cation. These include the geometries and binding energies of minima and transition states, the structure of solvation (sub)shells, the competition between various types of intermolecular bonding (p bonds versus H bonds), the change in the origin of the interaction as a function of the size of the Rg atom and the degree of solvation (induction versus charge transfer), the importance of monomer relaxation, the large angular-radial coupling and zero-point effects ...

Variable reaction coordinate transition state theory: Analytic results and application to the C2H3+H→C2H4 reaction

Abstract: A novel derivation is provided for the canonical, microcanonical, and energy E and total angular momentum J resolved reactive flux within the variable reaction coordinate transition state theory (VRC-TST) formalism. The use of an alternative representation for the reaction coordinate velocity yields a new expression for the kinematic factor which better illustrates its dependence on the pivot point location, and which can be straightforwardly evaluated. Also, the use of a geometric approach in place of an earlier algebraic one clarifies the derivation as does the use of Lagrange multiplier methodology for the analytic integration over the total angular momentum. Finally, a quaternion representation for the fragment and line-of-centers orientations is employed in place of the Euler angle or internal/external rotational coordinates used in prior studies. The result is an efficient, and particularly easy to implement, methodology for performing variable reaction coordinate transition state theory calculations. Furthermore, the simplicity of the derivation allows for the straightforward generalization to alternative forms for the dividing surface, as is illustrated by deriving the expressions for the cases of elliptical and planar dividing surfaces. Application to the C2H3+H reaction yields results for the total rate coefficient that are generally only 15% greater than those obtained from related trajectory simulations, thereby demonstrating the accuracy of the VRC-TST formalism. Meanwhile, results for the two separate addition channels (frontside and backside) illustrate the difficulty of accurately apportioning the total flux and particularly the inadequacy of canonical predictions for the channel specific optimized dividing surfaces.

A Periodic DFT Study of Isobutene Chemisorption in Proton-Exchanged Zeolites: Dependence of Reactivity on the Zeolite Framework Structure

Abstract: Isobutene chemisorption within proton-exchanged zeolites is investigated using periodic density functional theory method. This allows us to consider the effect of the zeolite micropore dimension to reactivity. The isobutene reaction pathways that proceed through primary and tertiary carbocation-like transition states have been investigated. The results agree with predicted reactivity trends. Activation energies of isobutene chemisorption are estimated to be around 100 and 25 kJ/mol for primary and tertiary transition states, respectively. Destabilization of transition state complexes and products are as observed before. Interestingly, because of the steric constraints, the chemisorbed alkoxy species appeared to become as unstable as protonated hydrocarbons. The more significant result is the correlation of the zeolite micropore dimension with activation energies. Fluctuations of the activation energies are observed as a function of the match of the transition state structures with the zeolite cavities. We...

Racemization barriers of 1,1'-binaphthyl and 1,1'-binaphthalene-2,2'-diol: a DFT study.

Abstract: Density functional theory has been applied to the study of various pathways and transition states for the configurational inversion of 1,1'-binaphthyl (1) and 1,1'-binaphthalene-2,2'-diol (2). The preferred pathway is found to be anti with centrosymmetric transition state. Whereas the reaction path of 1 goes downhill from transition to ground state, in the case of 2 it contains one unexpected local minimum. Very satisfactory agreement with available experimental values of activation Gibbs energies is achieved.

Scratching the surface of buckminsterfullerene: the barriers for Stone-Wales transformation through symmetric and asymmetric transition states.

Abstract: General-gradient approximation (PBE) and hybrid Hartree−Fock density functional theories (B3LYP) in conjunction with basis sets of up to polarized triple-ζ quality have been applied to study the Stone−Wales transformation of buckminsterfullerene (BF) to yield a C60 isomer of C2v symmetry with two adjacent pentagons (#1809). In agreement with earlier investigations, two different transition states and reaction pathways could be identified for the rearrangement from BF to C60-C2v on the C60 potential energy surface (PES). One has C2 molecular point group symmetry with the two migrating carbon atoms remaining close to the fullerene surface. The other one has a high-energy carbene-like (sp3) structure where a single carbon atom is significantly moved away from the C60 surface. The carbene intermediate and the second transition state along the stepwise reaction path characterized previously at lower levels of theory do not exist as stationary points with the density functionals utilized here. The classical bar...

Thermodynamic Properties and Kinetic Parameters for Cyclic Ether Formation from Hydroperoxyalkyl Radicals

Abstract: Rates and thermochemistry for the cyclization of various hydroperoxyalkyl radicals •QOOH with up to six carbons to form cyclic ethers plus OH are computed using complete-basis-set (CBS) and density-functional theory (DFT) methods. Effects of mono- and dialkyl substitution α to the OOH group and β to the radical center were also studied. Many quantum chemical methods have difficulty accurately predicting peroxide energetics and particular problems with the transition state calculations. The popular B3LYP method underestimates many barrier heights as well as O−O bond strengths by up to 8 kcal/mol. The related BH&HLYP method appears to give more accurate barrier heights predictions than B3LYP, but its thermochemistry is inaccurate and it overestimates the heats of reaction by up to 5 kcal/mol. For the transition states, there are subtle problems even with high-level CBS methods. But from the many calculations, a consistent picture emerges and is compared with the limited existing experimental data. Improved ...

A spin-orbit coupling study on the spin inversion processes in the direct methane-to-methanol conversion by FeO+

Abstract: Possible spin inversion processes in the direct conversion of methane to methanol by the bare FeO+ complex are discussed by means of spin–orbit coupling (SOC) calculations This reaction proceeds via two transition states (TSs) in the following way; FeO++CH4→FeO+(CH4)→[TS1]→HO–Fe+−CH3→[TS2]→Fe+(CH3OH)→Fe++CH3OH B3LYP density functional theory calculations show that the potential energies in the quartet and sextet states lie close and involve three crossing seams that can provide a chance of spin-forbidden transition The spin-forbidden transition leads to a significant decrease in the barrier heights of TS1 and TS2 that correspond to the hydrogen atom abstraction and the methyl shift, respectively To evaluate the spin-forbidden transition in the reaction pathway, the SOC matrix elements are calculated along the intrinsic reaction coordinate of the reaction The SOC analysis along the IRC is useful to look at how the FeO+/CH4 reacting system changes its spin multiplicity between the sextet and quartet surfaces The strength of the SOC between the low-lying quartet state and the sextet state is 1336 cm−1 in the reactant complex FeO+(CH4), 214 cm−1 in the hydroxo intermediate HO–Fe+–CH3, and 03 cm−1 in the product complex Fe+(CH3OH) Since the SOC value decreases along the oxidation process, the ease of spin inversion probability is the first crossing seam, the second crossing seam, and the third crossing seam, in this order

Enzymatic transition state poise and transition state analogues.

Abstract: The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (ANDN or SN2), aromatic nucleophilic displacements (AN*DN or SNAr), and both concerted and stepwise dissociative nucleophilic displacements (DNAN and DN*AN; SN1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (SN2 or DNAN) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric n...

Synthesis of second-generation transition state analogues of human purine nucleoside phosphorylase.

Abstract: Purine nucleoside phosphorylases (PNPs) catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the fixed purine and phosphate nucleophiles. As the phosphorolysis reaction progresses along the reaction coordinate, the distance between the purine and carbocation increases and the distance between carbocation and phosphate anion decreases. Immucillin-H and Immucillin-G have been shown previously to be potent inhibitors of PNP. We now report the synthesis of a second generation of stable transition state analogues, DADMe-Immucillins 2, 3, and 4, with increased distance between ribooxacarbenium and purine mimics by incorporation of a methylene bridge between these groups. These compounds are potent inhibitors with equilibrium dissociation constants as low as 7 pM against human PNP. Stable chemical analogues of enzymatic transition states are necessarily imperfect since they lack the partial bond character of the transition state. The immucillins and DADMe-Immu...

Computational study of the aminolysis of esters. The reaction of methylformate with ammonia.

Abstract: The aminolysis of esters is a basic organic reaction considered as a model for the interaction of carbonyl group with nucleophiles. In the present computational study the different possible mechanistic pathways of the reaction are reinvestigated by applying higher level electronic structure theory, examining the general base catalysis by the nucleophile, and a more comprehensive study the solvent effect. Both the ab initio QCISD/6-31(d,p) method and density functional theory at the B3LYP/6-31G(d) level were employed to calculate the reaction pathways for the simplest model aminolysis reaction between methylformate and ammonia. Solvent effects were assessed by the PCM method. The results show that in the case of noncatalyzed aminolysis the addition/elimination stepwise mechanism involving two transition states and the concerted mechanism have very similar activation energies. However, in the case of catalyzed aminolysis by a second ammonia molecule the stepwise mechanism has a distinctly lower activation energy. All transition states in the catalyzed aminolysis are 10-17 kcal/mol lower than those for the uncatalyzed process.

Effects of Microsolvation on the Structures and Reactions of Neutral and Zwitterion Alanine: Computational Study

Abstract: Calculations are presented for the structures and the reactions of various conformers of the bare alanine, neutral alanine−(H2O)n, and alanine zwitterion−(H2O)n (n = 1 and 2) clusters. The effects of the binding water molecules on the relative thermodynamic stability and the isomerization reaction of alanine are examined. Hydrogen bonding between alanine and the water molecule(s) may significantly affect the thermodynamic stability of conformers of the neutral alanine−(H2O)n (n = 1 and 2). clusters. Detailed analysis is presented on the isomerization (proton transfer) pathways between the neutral alanine−(H2O)2 and the alanine zwitterion−(H2O)2 clusters including the structures of the transition states by carrying out the intrinsic reaction coordinate analysis. We find that at least two water molecules need to bind to produce the stable alanine zwitterion−water cluster in the gas phase. The isomerization reaction for the alanine−(H2O)2 cluster proceeds by the concerted double proton-transfer mechanism via...

Ab Initio Study on the Mechanism of the Atmospheric Reaction OH+O3→HO2+O2

Abstract: The atmospheric reaction (1) OH + O 3 → + O 2 was investigated theoretically by using MP2, QCISD, QCISD(T), and CCSD(T) methods with various basis sets. At the highest level of theory, namely, QCISD, the reaction is direct, with only one transition state between reactants and products. However, at the MP2 level, the reaction proceeds through a two-step mechanism and shows two transition states, TS1 and TS2, separated by an intermediate, Int. The different methodologies employed in this paper consistently predict the barrier height of reaction (1) to be within the range 2.16 - 5.11 kcal mol -1 , somewhat higher than the experimental value of 2.0 kcal mol -1 .

Is the ruthenium analogue of compound I of cytochrome p450 an efficient oxidant? A theoretical investigation of the methane hydroxylation reaction.

Abstract: High-valent metal-oxo complexes catalyze C-H bond activation by oxygen insertion, with an efficiency that depends on the identity of the transition metal and its oxidation state. Our study uses density functional calculations and theoretical analysis to derive fundamental factors of catalytic activity, by comparison of a ruthenium-oxo catalyst with its iron-oxo analogue toward methane hydroxylation. The study focuses on the ruthenium analogue of the active species of the enzyme cytochrome P450, which is known to be among the most potent catalysts for C-H activation. The computed reaction pathways reveal one high-spin (HS) and two low-spin (LS) mechanisms, all nascent from the low-lying states of the ruthenium-oxo catalyst (Ogliaro, F.; de Visser, S. P.; Groves, J. T.; Shaik, S. Angew. Chem. Int. Ed. 2001, 40, 2874-2878). These mechanisms involve a bond activation phase, in which the transition states (TS's) appear as hydrogen abstraction species, followed by a C-O bond making phase, through a rebound of the methyl radical on the metal-hydroxo complex. However, while the HS mechanism has a significant rebound barrier, and hence a long lifetime of the radical intermediate, by contrast, the LS ones are effectively concerted with small barriers to rebound, if at all. Unlike the iron catalyst, the hydroxylation reaction for the ruthenium analogue is expected to follow largely a single-state reactivity on the LS surface, due to a very large rebound barrier of the HS process and to the more efficient spin crossover expected for ruthenium. As such, ruthenium-oxo catalysts (Groves, J. T.; Shalyaev, K.; Lee, J. In The Porphyrin Handbook; Biochemistry and Binding: Activation of Small Molecules, Vol. 4; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; pp 17-40) are expected to lead to more stereoselective hydroxylations compared with the corresponding iron-oxo reactions. It is reasoned that the ruthenium-oxo catalyst should have larger turnover numbers compared with the iron-oxo analogue, due to lesser production of suicidal side products that destroy the catalyst (Ortiz de Montellano, P. R.; Beilan, H. S.; Kunze, K. L.; Mico, B. A. J. Biol. Chem. 1981, 256, 4395-4399). The computations reveal also that the ruthenium complex is more electrophilic than its iron analogue, having lower hydrogen abstraction barriers. These reactivity features of the ruthenium-oxo system are analyzed and shown to originate from a key fundamental factor, namely, the strong 4d(Ru)-2p(O,N) overlaps, which produce high-lying pi(Ru-O), sigma(Ru-O), and sigma(Ru-N) orbitals and thereby to lead to a preference of ruthenium for higher-valent oxidation states with higher electrophilicity, for the effectively concerted LS hydroxylation mechanism, and for less suicidal complexes. As such, the ruthenium-oxo species is predicted to be a more robust catalyst than its iron-oxo analogue.

Large chiral recognition in hydrogen-bonded complexes and proton transfer in pyrrolo[2,3-b]pyrrole dimers as model compounds.

Abstract: The chiral recognition in the formation of hydrogen-bonded (HB) dimers of 1,6a-dihydropyrrolo[2,3-b]pyrrole derivatives as well as in their proton-transfer processes have been studied by means of ab initio calculations. The heterochiral dimers are in general the most stable ones, but amphiprotic substituents that are able to form attactive interactions with twin groups revert this tendency. Energy differences up to 4.0 kcal/mol have been found favoring the homo- or heterochiral complexes. Two possible proton-transfer processes have been studied, the concerted one and the nonconcerted one. The compresion of the systems in the transition structures produce an increase in the energetic differences when compared to the corresponding minima complexes. A Steiner-Limbach relationship has been found for the geometrical properties of the HB in the minima and transition states calculated here. The electron density and its Laplacian at the bond critical point have been found to correlate with the HB distance.

Modeling the Oxidative Degradation of Azo Dyes: A Density Functional Theory Study

Abstract: In this paper, we show, using DFT methods, reactivity indices, and electron density topology, that oxidative degradation of azo dyes occurs through the cleavage of the N−N bond following hydroxyl radical addition to the chromophore. Structures for both experimentally proposed reaction pathways, involving either cleavage of the C−N or N−N bonds, have been optimized at the B3LYP/6-31G(d) level of theory; the energies were further refined using single point calculations at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Potential energy surfaces (PES) have been compared for the two mechanisms to determine which mechanism is energetically more favorable. Reactivity indices and electron density topology calculations confirmed the findings of the PES. Detailed electron density contour mapping allowed accurate visualization of the electron distribution, i.e., its topology, for the transition states. The effect of the medium dielectric constant was allowed for via self-consistent reaction field (SCRF) theory calcul...

Thermal decomposition of ethanol. II. A computational study of the kinetics and mechanism for the H+C2H5OH reaction

Abstract: The kinetics and mechanism for the H+C2H5OH reaction, a key chain-propagation step in the high temperature decomposition and combustion of ethanol, have been investigated with the modified GAUSSIAN -2 (G2M) method using the structures of the reactants, transition states and products optimized at the B3LYP/6-311+G(d,p) level of theory. Four transition states have been identified for the production of H2+CH3CHOH (TS1), H2+CH2CH2OH (TS2), H2+C2H5O (TS3), and H2O+C2H5 (TS4) with the corresponding barriers, 7.18, 13.30, 14.95, and 27.10 kcal/mol. The predicted rate constants and branching ratios for the three H-abstraction reactions have been calculated over the temperature range 300–3000 K using the conventional and variational transition state theory with quantum-mechanical tunneling corrections. The predicted total rate constant, kt=3.15×103T3.12 exp(−1508/T) cm3 mol−1 s−1, agrees reasonably with existing experimental data; in particular, the result at 423 K was found to agree quantitatively with an availab...

Watching Photoinduced Chemistry and Molecular Energy Flow in Solution in Real Time

Abstract: Energized molecules are the essential actors in chemical transformations in solution As the rearrangement of bonds requires a movement of nuclei, vibrational energy is often the driving force for a reaction Vibrational energy can be redistributed within the "hot" molecule, or relaxation can occur when molecules interact Both processes govern the rates, pathways, and quantum yields of chemical transformations in solution Unfortunately, energy transfer and the breaking, formation, and rearrangement of bonds take place on ultrafast timescales This Review highlights experimental approaches for the direct, ultrafast measurement of photoinduced femtochemistry and energy flow in solution In the first part of this Review, we summarize recent experiments on intra- and intermolecular energy transfer The second part discusses photoinduced decomposition of large organic peroxides, which are used as initiators in free radical polymerization The mechanisms and timescales of their decarboxylation determine the initial steps of polymerization and the microstructure of the polymer product

Ab initio study of the mechanism of the atmospheric reaction: NO2 + O3 --> NO3 + O2.

Abstract: The atmospheric reaction NO2 + O3 --> NO3 + O2 (1) has been investigated theoretically by using the MP2, G2, G2Q, QCISD, QCISD(T), CCSD(T), CASSCF, and CASPT2 methods with various basis sets. The results show that the reaction pathway can be divided in two different parts at the MP2 level of theory. At this level, the mechanism proceeds along two transition states (TS1 and TS2) separated by an intermediate, designated as A. However, when the single-reference higher correlated QCISD methodology has been employed, the minimum A and the transition state TS2 are not found on the hypersurface of potential energy, which confirms a direct reaction mechanism. Single-reference high correlated and multiconfigurational methods consistently predict the barrier height of reaction (1) to be within the range 2.5-6.1 kcal mol(-1), in reasonable agreement with experimental data. The calculated reaction enthalpy is -24.6 kcal mol(-1) and the reaction rate calculated at the highest CASPT2 level, of k = 6.9 x 10(-18) cm(3) molecule(-1) s(-1). Both results can be regarded also as accurate predictions of the methodology employed in this article.

Over-the-barrier transition state analogues and crystal structure with mycobacterium tuberculosis purine nucleoside phosphorylase

Abstract: Stable chemical analogues of enzymatic transition states are imperfect mimics since they lack the partial bond character of the transition state. We synthesized structural variants of the Immucillins as transition state analogues for purine nucleoside phosphorylase and characterized them with the enzyme from Mycobacterium tuberculosis (MtPNP). PNPs form transition states with ribooxacarbenium ion character and catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the enzymatically immobilized purine and phosphate nucleophiles. As bond-breaking progresses, carbocation character builds on the ribosyl group, the distance between the purine and the carbocation increases, and the distance between carbocation and phosphate anion decreases. Transition state analogues were produced with carbocation character and increased distance between the ribooxacarbenium ion and the purine mimics by incorporating a methylene bridge between these groups. Immucillin-H (ImmH), DADMe-ImmH, and DADMe-ImmG mimic the transition state of MtPNP and are slow-onset, tight-binding inhibitors of MtPNP with equilibrium dissociation constants of 650, 42, and 24 pM. Crystal structures of MtPNP complexes with ImmH and DADMe-ImmH reveal an ion-pair between the inhibitor cation and the nucleophilic phosphoryl anion. The stronger ion-pair (2.7 A) is found with DADMe-ImmH. The position of bound ImmH resembles the substrate side of the transition state barrier, and DADMe-ImmH more closely resembles the product side of the barrier. The ability to probe both substrate and product sides of the transition state barrier provides expanded opportunities to explore transition state analogue design in N-ribosyltransferases. This approach has resulted in the highest affinity transition state analogues known for MtPNP.

Acrylate formation via metal-assisted C-C coupling between CO2 and C2H4: reaction mechanism as revealed from density functional calculations.

Abstract: The reaction path for the formation of a binuclear hydrido-acrylate complex in a CO2−C2H4 coupling process is explored in detail by locating the key intermediates and transition states on model potential energy surfaces derived from density functional calculations on realistic models. The formation of the new C−C bond is shown to take place via oxidative coupling of coordinated CO2 and C2H4 ligands resulting in a metalla-lactone intermediate, which can rearrange to an agostic species allowing for a β-hydrogen shift process. The overall reaction is predicted to be clearly exothermic with all intermediates lying below the reactants in energy, and the highest barrier steps correspond to C−C coupling and β-hydrogen transfer. The phosphine ligands are found to play an important role in various phases of the reaction as their dissociation controls the coordination of CO2, the formation of the agostic intermediate, and the dimerization process; furthermore, their presence facilitates the oxidative coupling by su...

Regioselectivity in aromatic Claisen rearrangements.

Abstract: Theoretical calculations and the isomeric product composition for a series of eight meta-substituted allyl aryl ethers confirm the reliability of a new (1)H NMR methodology used to predict aromatic Claisen regioselectivity from ground-state conformational preference of the reactant allyloxy group. Frontier HOMO-LUMO intramolecular orbital interactions, a classical approach in predicting reactivity and selectivity for Claisen rearrangements of allyl vinyl ethers, is shown to fail to mimic transition-state orbital interactions for aromatic Claisen rearrangements of meta-substituted allyl aryl ethers. B3LYP/6-31G(d,p) calculations on reactants and transition states are shown, however, to correctly predict the outcome of such aromatic Claisen rearrangements from either the preferential reactant ground-state conformation (theoretical predictions that agree with the NMR measurements) or the less energetic transition state, or both.