Calculated Reaction Pathways Research Articles

Aryl C–H Amination by Diruthenium Nitrides in the Solid State and in Solution at Room Temperature: Experimental and Computational Study of the Reaction Mechanism

Diruthenium azido complexes Ru(2)(DPhF)(4)N(3) (1a, DPhF = N,N'-diphenylformamidinate) and Ru(2)(D(3,5-Cl(2))PhF)(4)N(3) (1b, D(3,5-Cl(2))PhF = N,N'-bis(3,5-dichlorophenyl)formamidinate) have been investigated by thermolytic and photolytic experiments to investigate the chemical reactivity of the corresponding diruthenium nitride species. Thermolysis of 1b at ~100 °C leads to the expulsion of N(2) and isolation of Ru(2)(D(3,5-Cl(2))PhF)(3)NH(C(13)H(6)N(2)Cl(4)) (3b), in which a nitrogen atom has been inserted into one of the proximal aryl C-H bonds of a D(3,5-Cl(2))PhF ligand. A similar C-H insertion product is obtained upon thawing a frozen CH(2)Cl(2) solution of the nitride complex Ru(2)(DPhF)(4)N (2a), formed via photolysis at -196 °C of 1a to yield Ru(2)(DPhF)(3)NH(C(13)H(10)N(2)) (3a). Evidence is provided here that both reactions proceed via direct intramolecular attack of an electrophilic terminal nitrido nitrogen atom on a proximal aryl ring. Thermodynamic and kinetic data for this reaction are obtained from differential scanning calorimetric measurements and thermal gravimetric analysis of the thermolysis of Ru(2)(D(3,5-Cl(2))PhF)(4)N(3), and by Arrhenius/Eyring analysis of the conversion of Ru(2)(DPhF)(4)N to its C-H insertion product, respectively. These data are used to develop a detailed, experimentally validated DFT reaction pathway for N(2) extrusion and C-H functionalization from Ru(2)(D(3,5-Cl(2))PhF)(4)N(3). The diruthenium nitrido complex is an intermediate in the calculated reaction pathway, and the C-H functionalization event shares a close resemblance to a classical electrophilic aromatic substitution mechanism.

Reaction Mechanism of Monoethanolamine with CO2 in Aqueous Solution from Molecular Modeling

We present a theoretical study of the reaction mechanism of monoethanolamine (MEA) with CO₂ in an aqueous solution. We have used molecular orbital reaction pathway calculations to compute reaction free energy landscapes for the reaction steps involved in the formation of carbamic acids and carbamates. We have used the conductor-like polarizable continuum model to calculate reactant, product, and transition state geometries and vibrational frequencies within density functional theory (DFT). We have also computed single point energies for all stationary structures using a coupled cluster approach with singles, doubles, and perturbational triple excitations using the DFT geometries. Our calculations indicate that a two-step reaction mechanism that proceeds via a zwitterion intermediate to form carbamate is the most favorable reaction channel. The first step, leading to formation of the zwitterion, is found to be rate-determining, and the activation free energies are 12.0 (10.2) and 11.3 (9.6) kcal/mol using Pauling (Bondi) radii within the CPCM model at the CCSD(T)/6-311++G(d,p) and CCSD(T)/6-311++G(2df,2p) levels of theory, respectively, using geometries and vibrational frequencies obtained at the B3LYP/6-311++G(d,p) level of theory. These results are in reasonable agreement with the experimental value of about 12 kcal/mol. The second step is an acid-base reaction between a zwitterion and MEA. We have developed a microkinetic model to estimate the effective reaction order at intermediate concentrations. Our model predicts an equilibrium concentration for the zwitterion on the order of 10⁻¹¹ mol/L, which explains why the existence of the zwitterion intermediate has never been detected experimentally. The effective reaction order from our model is close to unity, also in agreement with experiments. Complementary ab initio QM/MM molecular dynamics simulations with umbrella sampling have been carried out to determine the free energy profiles of zwitterion formation and proton transfer in solution; the results confirm that the formation of the zwitterion is rate-determining.

GeCl2 cycloaddition reactions to unsaturated organic compounds taking ethylene, buta-1,3-diene, and hexa-1,3,5-triene as examples: a quantum chemical study

The cycloaddition reactions of dichlorogermylene GeCl2 to ethylene, buta-1,3-diene, and hexa-1,3,5-triene were studied within the framework of the density functional theory (PBE and B3LYP density functionals) and by the ab initio CBS-QB3 method. The energy characteristics of the reaction of GeCl2 with ethylene were refined and non-empirical quantum chemical calculations of reaction pathways in the GeCl2 + buta-1,3-diene and GeCl2 + hexa-1,3,5-triene systems were carried out for the first time. It was shown that the [2+1] cycloaddition reactions are kinetically hindered and thermodynamically unfavorable, while the [4+1] and [6+1] cycloaddition reactions are characterized by low barriers and result in thermodynamically favorable products. For the [4+1] cycloaddition to buta-1,3-diene and [6+1] cycloaddition to hexa-1,3,5-triene, the most energetically favorable reaction pathways involve a suprafacial and antarafacial approach of reactants, respectively.

Nanoscale fracture in graphene

Fracture of a monolayer graphene is governed by the competition between bond breaking and bond rotation at a crack tip. Using atomistic reaction pathway calculations, we identify a kinetically favorable fracture path that features an alternating sequence of bond rotation and bond breaking. Our results suggest that the mechanical cracking can create fracture edges with nanoscale morphologies due to the non-uniform bond deformation and rupture induced by the localized high stresses near the crack tip. Such fractured edges may provide a structural basis of tailoring the electronic properties of graphene either intrinsically or by further edge functionalization.

Ligand exchange reactions in Cu(iii) complexes: mechanistic insights by combined NMR and DFT studies

NMR studies of (13)C/(12)C isotopic patterns in Cu(iii) intermediates and reaction products together with DFT calculations of possible reaction pathways indicate an intermolecular S(N)2 like substitution mechanism for ligand exchange reactions in square planar Cu(iii) complexes, which is proposed to be slow compared to reductive elimination at synthetic conditions.

Application of quantum chemical calculations to two non-trivial cases in the field of molecular spectroscopy

In this paper, we illustrate the contribution of the quantum chemical calculations to the simulation of two types of spectra. In a first part, the calculations of theoretical resonance Raman spectra of transient species are presented. The comparison of the theoretical and experimental spectra allows validating the methodology. From calculation results, the molecular structure and the spectra assignment of radicals have been deduced. In a second part, the TD-DFT methodology is applied to the determination of the preferential chelating site involved in the metal fixation by a ligand possessing several complexing functions in competition. We show that the use of UV-visible spectroscopy combined with quantum chemical calculations is well adapted to resolve the molecular structure of a complex. The reaction pathway calculations allow a better understanding of the regioselectivity of the complexation mechanism.

Design of transition-state analogues for gaba-transaminase

Compounds which inhibit the mitochondrial enzyme GABA-transaminase have considerable potential as anticonvulsant drugs. An approach which may provide potent and specific enzyme inhibitors involves the use of the transition-state structure of the reaction catalyzed by the enzyme as a template for the design of transition-state analogues. Molecular orbital calculations have been used to calculate the potential energy surface and identify the transition-state structure for the reaction catalyzed by GABA-transaminase. A series of transition-state analogues based on this structure have been synthesized and were found to be biologically active. An active site model has also been developed on the basis of the calculated reaction pathway.

Gas phase self-association of Eudistomin U controlled by gas phase acidity and origin of its interaction with nucleobases

Electrospray ionization mass spectrometry was used to investigate the intrinsic chemical properties of β-carbolines: Eudistomin U (as EU) and 5-Br-Eudistomin U (as BrEU) yielding self-association in negative ion mode. It was observed that the deprotonated homodimer of EU was more stable in the gas phase than BrEU. Indeed, BrEU presents a higher polarizability that could influence the dimerization energy. On the contrary, the stability energies calculated at B3LYP/6-31+G*//AM1 level showed a small difference for these two dimers. To understand the experimental stability variation, the experimental and theoretical gas phase acidities of these two β-carbolines have been estimated. It has been shown that EU is less acidic than BrEU in the gas phase, which could explain the lower stability of the [2BrEU-H] − dimer. In addition, the investigation of non-covalent interaction of β-carbolines and nucleobases has been carried out. It was experimentally demonstrated that the deprotonated heterodimer's relative stability scale was [Gua + M−H] − >> [Thy + M−H] − > [Ade + M−H] −, but the Cyt/β-carboline complexes were not observed. However, the absence of Cyt/β-carboline complexes could be explained by the great acidity difference between Cyt and β-carbolines, yielding unstable non-covalent complexes. The studied β-carbolines showed a particular affinity with guanine which suggested a strong interaction, from a structural and reactivity point of view. Calculated reaction pathways rationalize the set of experimental results concerning the heterodimer stabilisation reflected by the V 1/2 value of breakdown curves of deprotonated heterodimers.

Selective Scanning Tunnelling Microscope Electron-Induced Reactions of Single Biphenyl Molecules on a Si(100) Surface

Selective electron-induced reactions of individual biphenyl molecules adsorbed in their weakly chemisorbed configuration on a Si(100) surface are investigated by using the tip of a low-temperature (5 K) scanning tunnelling microscope (STM) as an atomic size source of electrons. Selected types of molecular reactions are produced, depending on the polarity of the surface voltage during STM excitation. At negative surface voltages, the biphenyl molecule diffuses across the surface in its weakly chemisorbed configuration. At positive surface voltages, different types of molecular reactions are activated, which involve the change of adsorption configuration from the weakly chemisorbed to the strongly chemisorbed bistable and quadristable configurations. Calculated reaction pathways of the molecular reactions on the silicon surface, using the nudge elastic band method, provide evidence that the observed selectivity as a function of the surface voltage polarity cannot be ascribed to different activation energies. These results, together with the measured threshold surface voltages and the calculated molecular electronic structures via density functional theory, suggest that the electron-induced molecular reactions are driven by selective electron detachment (oxidation) or attachment (reduction) processes.

Potential Energy Surface of Methanol Decomposition on Cu(110)

Combining the dimer saddle point searching method and periodic density functional theory calculations, the potential energy surface of methanol decomposition on Cu(110) has been mapped out. Each elementary step in the methanol decomposition reaction into CO and hydrogen occurs via one of three possible mechanisms: O−H, C−H, or C−O bond scission. Multiple reaction pathways for each bond scission have been identified in the present work. Reaction pathway calculations are started from an initial (reactant) state with methanol adsorbed in the most stable geometry on Cu(110). The saddle point and corresponding final state of each reaction or diffusion mechanism were determined without assuming the reaction mechanism. In this way, the reaction paths are determined without chemical intuition. The harmonic pre-exponential factor of each identified reaction is calculated from a normal-mode analysis of the stationary points. Then, using harmonic transition state theory, the rate constant of each identified reaction...

Mechanics of nanocrack: Fracture, dislocation emission, and amorphization

Understanding the nanoscale fracture mechanisms is critical for tailoring the mechanical properties of materials at small length scales. We perform an atomistic study to characterize the formation and extension of nano-sized cracks. By using atomistic reaction pathway calculations, we determine the energetics governing the brittle and ductile responses of an atomically sharp crack in silicon, involving the competing processes of cleavage bond breaking, dislocation emission, and amorphization by the formation of five- and seven-membered rings. We show that the nanoscale fracture process depends sensitively on the system size and loading method. Our results offer new perspectives on the brittle-to-ductile transition of fracture at the nanoscale.

Theoretical study of cyclohexane hydroxylation by three possible isomers of [FeIV(O)(R-TPEN)]2+: does the pentadentate ligand wrapping around the metal center differently lead to the different stability and reactivity?

Density functional theory calculations have been carried out to elucidate the mechanism of cyclohexane hydroxylation by three possible isomers of [Fe(IV)(O)(N-R-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine)](2+) (R is methyl or benzyl) (Klinker et al. in Angew Chem Int Ed 44:3690-3694, 2005). The calculations offer a mechanistic view and reveal the following features: (a) all the three isomers possess triplet ground states and low-lying quintet excited states, (b) the relative stability follows the order isomer A > isomer B > isomer C, in agreement with the conclusions of Klinker et al., (c) the theoretical investigations provide a rationale to explain the interconversion of the three isomers, (d) the reaction pathways of the C-H hydroxylation are initiated by a hydrogen-abstraction step, and (e) the three isomers react with cyclohexane via two-state-reactivity patterns on competing triplet and quintet spin-state surfaces. As such, in the gas phase, the relative reactivity exhibits the trend isomer B > isomer A, while at the highest level, B2//B1 with zero point energy and solvation corrections, the relative reactivity follows the order isomer B > isomer A > isomer C. Thus, the calculated reaction pathway shows that pyridine rings perpendicular to the Fe-O axis result in more reactive species, and a pyridine ring coordinated trans to the oxygen atom leads to the least reactive isomer.

Quantum Chemical Approach to the Mechanism for the Biological Conversion of Tyrosine to Dopaquinone

Tyrosinase catalyzes the biological conversion of tyrosine to dopaquinone with dioxygen at the dinuclear copper active site under physiological conditions. On the basis of the recent X-ray crystal structural analysis of tyrosinase (J. Biol. Chem. 2006, 281, 8981), a possible mechanism for the catalytic cycle of tyrosinase is proposed by using quantum mechanical/molecular mechanical calculations, which can reasonably take effects of surrounding amino-acid residues, hydrogen bonding, and protein environment into account. The (mu-eta2:eta2-peroxo)dicopper(II) species plays a role in a series of elementary processes mediated by the dicopper species of tyrosinase. A stable phenoxyl radical is involved in the reaction pathway. The catalysis has five steps of proton transfer from the phenolic O-H bond to the dioxygen moiety, O-O bond dissociation of the hydroperoxo species, C-O bond formation at an ortho position of the benzene ring, proton abstraction and migration mediated by His54, and quinone formation. The energy profile of the calculated reaction pathway is reasonable in energy as biological reactions that occur under physiological conditions. Detailed analyses of the energy profile demonstrate that the O-O bond dissociation is the rate-determining step. The activation energy for the O-O bond dissociation at the dicopper site is computed to be 14.9 kcal/mol, which is in good agreement with a measured kinetic constant. As proposed recently, the His54 residue, which is flexible because it is located in a loop structure in the protein, would play a role as a general base in the proton abstraction and migration in the final stages of the reaction to produce dopaquinone.

Fundamental theories and their empirical patches

Many theories require empirical patches or ad hoc assumptions to work properly in application to chemistry. Some examples include the Bohr quantum theory of atomic spectra, the Pauli exclusion principle, the Marcus theory of the rate-equilibrium correlation, Kekule’s hypothesis of bond oscillation in benzene, and the quantum calculation of reaction pathways. Often the proposed refinements do not grow out of the original theory but are devised and added ad hoc. This brings into question the goal of constructing theories derived from first principles and the concept of ranking the merit of theories according to their freedom from empirical contamination.

Mechanistic insights on the site selectivity in successive 1,3-dipolar cycloadditions to meso-tetraarylporphyrins

A DFT study on site selectivity in successive 1,3-dipolar cycloadditions of meso-tetraarylporphyrins with azomethine ylide and N-methylnitrone has been carried out. The calculation of the thermodynamic stability of both ylide and nitrone-derived adducts reveals that bacteriochlorins are more stable and have stronger aromatic character than isobacteriochlorins. Calculations of whole reaction pathways show that cycloadditions of azomethine ylide on porphyrin and its derived chlorin are irreversible and hence kinetically controlled. Solvent influence on the site selectivity of this reaction has also been considered, and appears to be decisive in controlling the site selectivity. In contrast, cycloadditions of nitrone over porphyrin and chlorin are clearly reversible, pointing to a thermodynamic control of these reactions.

A New Interpretation of the Reaction Pathway of Deprotonative Metalation with TMP−Zn-ate/TMEDA Complex [TMEDA·Na(μ-tBu)(μ-TMP)Zn(tBu)

Density functional theory (DFT) calculations of possible reaction pathways and mechanisms for the deprotonation of benzene with Mulvey's reagent, TMEDA.Na(micro-R)(micro-TMP)Zn(R) (TMEDA=N,N,N',N'-tetramethylethylenediamine, R = alkyl, TMP = 2,2,6,6-tetramethylpiperidide) indicate that the deprotonation of benzene with Mulvey's reagent proceeds through a stepwise mechanism, not a one-step mechanism. In the first step, deprotonation involving the TMP ligand on the reagent is kinetically more favorable than that involving the alkyl ligand.

The geochemical evolution of very dilute CO2‐rich water in Chungcheong Province, Korea: processes and pathways

AbstractA geochemical study was carried out on the CO2‐rich water occurring in granite areas of Chungcheong Province, Korea. In this area, very dilute and acidic CO2‐rich waters [62–242 mg l−1 in total dissolved solid (TDS), 4.0–5.3 in pH; group I) occur together with normal CO2‐rich waters (317–988 mg l−1 in TDS, 5.5–6.0 in pH; group II). The concentration levels and ages of group I water are similar to those of recently recharged and low‐mineralized groundwater (group III). Calculation of reaction pathways suggests that group I waters are produced by direct influx of CO2 gas into group III type waters. When the groundwater is injected with CO2, it develops the capacity to accept dissolved solids and it can evolve into water with very high solute concentrations. Whether the water is open or closed to the CO2 gases becomes less important in controlling the reaction pathway of the CO2‐rich groundwater when the initial pco2 is high. Our data show that most of the solutes are dissolved in the CO2‐rich groundwater at pH > 5 where the weathering rates of silicates are very slow or independent of pH. Thus, groundwater age is likely more important in developing high solute concentrations in the CO2‐rich groundwaters than accelerated weathering kinetics because of acidic pH caused by high pco2.

The hydrogenation and direct desulfurization reaction pathway in thiophene hydrodesulfurization over MoS 2 catalysts at realistic conditions: A density functional study

We present density functional theory (DFT) calculations of reaction pathways for both the hydrogenation (HYD) and direct desulfurization (DDS) routes in the hydrodesulfurization (HDS) of thiophene over the different MoS 2 edge structures, which will dominate under typical HDS reaction conditions. Contrary to the generally accepted view, we find that the HYD reaction path, which involves hydrogenation to 2-hydrothiophene followed by hydrogenation to 2,5-dihydrothiophene and subsequent S C scission, can occur at the equilibrium Mo( 10 1 ¯ 0 ) edge without the creation of coordinatively unsaturated Mo edge sites. This is related to the presence of the metallic-like brim sites also observed in previous STM studies. It is found that the HYD reaction pathway also can occur at the S( 1 ¯ 010 ) edge. At this edge, the equilibrium edge structure itself is not active, and sulfur vacancies must be created for the reaction to proceed. It is found that the effective energy barrier for vacancy creation depends on the H 2 partial pressure. The sulfur vacancies at the S( 1 ¯ 010 ) edge are also found to be active sites for the DDS pathway. This pathway does involve an initial hydrogenation step to 2-hydrothiophene, followed by S C scission. Analyzing the relative stabilities of reactants and intermediates suggests that a catalytic cycle may involve elementary steps that start at one type of edge and are completed at the other; for example, many intermediates are more stable at the S edge. The regeneration of the active sites is found to be a crucial step for all of the reaction pathways, and the importance of reactions at Mo brim sites is related to the observation that regeneration is least activated here. It is proposed that an important activity descriptor is the minimum energy required to either add or remove S from the different equilibrium edge structures.

Interfacial plasticity governs strain rate sensitivity and ductility in nanostructured metals

Nano-twinned copper exhibits an unusual combination of ultrahigh strength and high ductility, along with increased strain-rate sensitivity. We develop a mechanistic framework for predicting the rate sensitivity and elucidating the origin of ductility in terms of the interactions of dislocations with interfaces. Using atomistic reaction pathway calculations, we show that slip transfer reactions mediated by twin boundary are the rate-controlling mechanisms of plastic flow. We attribute the relatively high ductility of nano-twinned copper to the hardening of twin boundaries as they gradually lose coherency during plastic deformation. These findings provide insights into the possible means of optimizing strength and ductility through interfacial engineering.

Mechanistic aspects of proton chain transfer in the green fluorescent protein : Part II. A comparison of minimal quantum chemical models

In this paper we report the results of extensive quantum chemical reaction pathway calculations for the electronic ground state of several different cluster models that mimic the proton chain transfer path within the green fluorescent protein (GFP). Our principal objective is to establish the robustness with respect to variations in the model of our recent mechanistic inferences for the ground state proton chain transfer [S. Wang and S. C. Smith, J. Phys. Chem. B, 2006, 110, 5084]. Additionally, comparison of our ground state results with the excited state proton transfer (ESPT) study by Vendrell et al. [O. Vendrell, R. Gelabert, M. Moreno and J. M. Lluch, J. Am. Chem. Soc., 2006, 128, 3564] leads to the conclusion that the mechanism of proton chain transfer may be expected to be analogous in ground and excited states, principally because in both cases the loss of the chromophore's phenolic proton contributes strongly to the reaction coordinate only late in the reaction path.