High Activation Free Energy Research Articles

XNgNSi (X = HCC, F; Ng = Kr, Xe, Rn): A New Class of Metastable Insertion Compounds Containing Ng-C/F and Ng-N Bonds and Possible Isomerization therein.

Recently, astronomically important silaisocyanoacetylene (HCCNSi) possessing a large dipole moment has been detected for the first time with the help of crossed molecular beam experiments. Quantum chemical computations at higher levels of theory have also been performed to characterize the transient species. In this study, we have analyzed the equilibrium geometry, stability, reactivity, and energetics as well as the nature of bonding in the noble gas (Ng) inserted HCCNSi compound. We have also considered its F analogue to understand the influence of the most electronegative atom in the compound. Metastable behavior of the XNgNSi compounds (X = HCC, F; Ng = Kr-Rn) is examined by calculating thermochemical parameters like free energy change (ΔG) and zero-point-energy-corrected dissociation energy (D0) at 298 K for all possible two-body (2B) and three-body (3B) (both neutral as well as ionic) dissociation channels using coupled-cluster theory [CCSD(T)] in addition to density functional theory (DFT) as well as second order Møller-Plesset perturbation theory (MP2). The set of predicted compounds is found to be endergonic in nature, having high positive free energy change suggesting the thermochemical stability of the compounds except for the 2B Ng-release paths. Though thermodynamically feasible, they are kinetically protected with very high activation free energy barriers. Interestingly, the release of Ng from the parent moiety XNgNSi produces the XSiN isomer, by 180° flipping of the NSi moiety. This can also be seen in the dynamical simulation carried out with the help of atom-centered density matrix propagation (ADMP) technique at 2000K for 1 ps. The bonding in Ng-C, Ng-F, and Ng-N bonds of the studied compounds is analyzed and described with the aid of natural bond orbital (NBO), topological parameters computed using atoms-in-molecules theory (AIM), energy decomposition analysis (EDA), and adaptive natural density partitioning (AdNDP) methods. The natural charge distribution on the constituent atoms suggests that the compounds can be partitioned into both ways of representations, viz., neutral radical as well as ionic fragments. Lastly, the reactivity of the compounds is scrutinized using certain reactivity descriptors calculated within the domain of conceptual density functional theory (CDFT).

3-Benzylbenzothiazolylidene Carbene Catalyzed Isomerization of Dimethyl Maleate to Dimethyl Fumarate: Experimental and Theoretical Results

Background: N-Heterocyclic Carbenes (NHCs) have emerged as ubiquitous species having applications in a broad range of fields, including organocatalysis and organometallic chemistry. Since Arduengo and co-workers first isolated a bottlable NHC, namely imidazol-2-ylidene derivative, these nucleophilic species have attained a prominent place in synthetic organic chemistry. The NHC-induced non-asymmetric catalysis has turned out to be a really fruitful area of research in recent years. Methods and Results: The quantitative aspects of the experimental and theoretical investigation of isomerization of dimethyl maleate to dimethyl fumarate catalyzed by an N-heterocyclic carbene (NHC), namely 3-benzylbenzothiazolylidene are being reported for the first time. Dimethyl maleate on treating with 3-benzylbenzothiazolylidene carbene (10 mol%), generated in situ from the reaction of 3- benzylbenzothiazolium bromide with triethylamine in diethyl ether at room temperature under nitrogen atmosphere isomerizes quantitatively to dimethyl fumarate. Theoretical investigation of a model reaction scheme at the wB97XD/6-31+G(d) level reveals that initial attack of the carbene, which is the ratedetermining step, is followed by rotation about the C-C bond in preference to a higher activation free energy path involving proton abstraction. The species so formed splits off the carbene to yield dimethyl fumarate. Eyring equation has been used to rationalize the effect of temperature on the isomerization rate. Conclusions and Perspective: 3-Benzylbenzothiazolylidene carbene catalyzes the isomerization of dimethyl maleate to its trans-isomer. This carbene can be used in other catalytic reactions, such as acyloin condensation and Stetter reaction.

How does HOTf/HFIP Cooperative System Catalyze the Ring‐Opening Reaction of Cyclopropanes? A DFT Study

AbstractDensity functional theory calculations have been performed to probe the detailed mechanisms of Brønsted‐acid‐catalyzed ring‐opening reactions of donor‐acceptor cyclopropanes. The reaction model without consideration of the explicit solvation effect was characterized by a high activation free energy of 29.5 kcal/mol, while inclusion of the explicit solvation effect in calculations lowered the activation free energy to 20.5 kcal/mol, which demonstrated the cooperative role of HOTf and HFIP in facilitating the ring‐opening step. Additionally, we put forward two distinct reaction mechanisms, including the nucleophile‐induced mechanism and the protonation‐induced mechanism, for the ring‐opening step of donor‐acceptor cyclopropanes. Computational results revealed that modulation of the reaction conditions could result in the shift of the reaction mechanisms.

Proton Acceptor near the Active Site Lowers Dramatically the O-O Bond Formation Energy Barrier in Photocatalytic Water Splitting.

The O–O bond formation process via water nucleophilic attack represents a thermodynamic and kinetic bottleneck in photocatalytic water oxidation because of the considerably high activation free energy barrier. It is therefore of fundamental significance and yet challenging to find strategies to facilitate this reaction. The microscopic details of the photocatalytic water oxidation step involving the O–O bond formation in a catalyst–dye supramolecular complex are here elucidated by density functional theory-based Car–Parrinello molecular dynamics simulations in the presence of an extra proton acceptor. Introducing a proton acceptor group (OH–) in the hydration shell near the catalytic active site accelerates the rate-limiting O–O bond formation by inducing a cooperative event proceeding via a concerted proton-coupled electron-transfer mechanism and thus significantly lowering the activation free energy barrier. The in-depth insight provides a strategy for facilitating the photocatalytic water oxidation and for improving the efficiency of dye-sensitized photoelectrochemical cells.

Exploration of Unimolecular and Bimolecular Pathways for Nitrile N‐Oxide Isomerization to Isocyanate Through Global Reaction Route Mapping Techniques

Mechanisms of the unimolecular and bimolecular isomerization of nitrile N‐oxide to isocyanate were investigated by quantum chemical calculations using the global reaction route mapping (GRRM) technique, which consists of the anharmonic downward distortion following (ADDF) and multi‐component artificial force induced reaction (AFIR) methods, which can exhaustively search reaction paths. In the unimolecular isomerization, isomerization paths of nitrile N‐oxide to isocyanate were exhaustively explored by the ADDF method. The energetically lowest path for 2,6‐dimethoxybenzonitrile oxide (Ar–CNO) isomerization was via oxazirine intermediate formation, which was the rate‐determining step with an activation free energy of 56.8 kcal mol–1. The high activation free energy indicates that the isomerization hardly proceeds as a thermal unimolecular reaction. Next, the bimolecular isomerization paths of Ar–CNO were explored for diradical addition, [3+2] and [3+3] cycloadditions, and self‐catalyzed isomerization through the AFIR method. The diradical addition was the energetically lowest path with an activation free energy of 55.4 kcal mol–1. Although the bimolecular isomerization was energetically favorable than the unimolecular isomerization, its activation free energy was still high for the reaction to proceed under thermal conditions. Exhaustive path searching for these unimolecular and bimolecular isomerizations suggest that these reactions are catalyzed by acid or base.

The isomerization of cytosine: Intramolecular hydrogen atom transfer mediated through formic acid

AbstractThe catalytic ability of H2O and HCOOH to facilitate the tautomerism of KA to KIt isomer has been studied. It is shown that the direct tautomerism (path A) is unlikely because of the high activation free energy, whereas the presence of H2O and HCOOH (paths B and C) significantly contributes to decreasing the activation free energy. Meanwhile, the conventional transition state theory followed by Wigner tunneling correction is applied to estimate the rate constants. The rate constant with Wigner tunneling correction for direct tautomerization is obviously smaller than that of HCOOH‐mediated tautomerization, which is the most plausible mechanism. Finally, another important finding is that the ratio of reaction rates between direct tautomerism reaction and catalyst‐induced tautomerism increases with the increase of the catalyst concentration at a given temperature. The results of the present study demonstrate the feasibility of acid catalysis for DNA bases isomerization reaction that would otherwise be forbidden.

Revisited the mechanism of the transition metal catalyzed cycloetherification of ω-hydroxy propargylic ester: A DFT study

DFT calculations on a reported mechanistic pathway of a platinum catalyzed cycloetherification process reveal the requirement of high activation free energy for the progress of the reaction. Parallel calculations on some alternative pathways suggest that a solvent assisted proton transferring mechanism is much more likely to be relevant to explain the formation of the product. Our calculation also supports the experimental finding of the formation of a different product on replacing the platinum salt by a gold one.

Reduced State of Iridium PCP Pincer Complexes in Electrochemical CO2 Hydrogenation

We present a computational study on the mechanism for electrochemical reduction of CO2 using a PCP pincer iridium(III) dihydride complex. Our results point toward a mechanism that involves an in situ-generated iridium(I) hydride as the active species for the CO2 to formate reduction. The iridium(III) path can operate in parallel but is associated with higher activation free energies in the reaction between the metal hydride and CO2, compared to the reaction at the in situ-generated iridium(I) species.

THE INVESTIGATION OF OXIDATIVE DECOMPOSITION OF PHENYL ALANINE BY TRANSITION METAL IONS

The aim of this study is to comprehend the mechanism of the oxidative decomposition of phenylalanine (the simplest aromatic amino acid) by transition metals, in particular cobalt, using quantum mechanical tools. All the ground and transition state structures are optimized using the density functional method M06-2X. Additional calculations have been carried out using M06. Recently, a couple of works for profiling the transcriptomic data of the yeast Saccharomyces cerevisiae when exposed to transition metals, such as cobalt and nickel were done by Cakar and co-workers [1, 2]. According to their results, the cobalt-resistant mutants had a tendency to reduce the amount of aromatic amino acids, suggesting that Co3+, but not other metals, reacts specifically with aromatic amino acids, yielding harmful products. Although the in vitro decomposition of amino acids has been considered in numerous studies in the literature, the mechanism and intermediates formed during the reaction are not clear. The reactions use oxidizing agents such as diperiodatocuprate(III) in alkaline medium, or Mn3+ and its hydroxide form (Mn(OH)2+) in sulfuric acid medium [3, 4]. But the reaction of Co3+ with phenylalanine was not studied. In this study, it has been shown that cobalt (III) ions are powerful oxidizing agents against aromatic amino acids. Our study has revealed several pathways of the decomposition reaction of zwitterionic phenyl alanine at neutral pH and the effect of the Co3+ ion on the decomposition reaction. It was shown that the oxidation of phenylalanine by a Co3+ ion results in decarboxylation and deprotonation of phenylalanine. The presence of the aromatic ring facilitates the redox reaction. Then, oxidation by a second Co3+ in concert with the nucleophilic addition of an OH- ion leads to a pathway that yields phenyl acetaldehyde. A different pathway may proceed through oxidation by two more Co3+ ions and yield phenylacetamide. But this pathway has a higher activation free energy. Another possible decomposition pathway yielding phenylpyruvate also requires a considerably high reaction activation free energy. The reactions of Fe3+ and Ni3+ with phenylalanine have also been investigated. It has been found that these two transition metal ions are not suitable for the reactions mentioned above.

Theoretical investigations toward the tandem reactions of N-aziridinyl imine compounds forming triquinanes via trimethylenemethane diyls: mechanisms and stereoselectivity

In this paper, we have investigated the tandem reaction mechanism for the N-aziridinyl imine compounds forming triquinanes via trimethylenemethane (TMM) diyls in detail. Based on the calculated results, the reaction is initiated by the cleavage of the N-aziridinyl in the substrate, followed by an intramolecular 1,3-dipolar (3 + 2) cycloaddition preferentially leading to a linearly-fused tetrahydrocyclopentapyrazole intermediate. Next, the intermediate loses N2 to form the singlet TMM diyl M3S, which can then undergo another concerted (3 + 2) cycloaddition to generate the linearly-fused cis–trans or cis–syn triquinane products. In addition, M3S can also undergo intersystem crossing to the triplet TMM diyl M3T, and the six possible reaction pathways associated with M3T have also been identified. The calculated results reveal that the cis–trans fused pathway associated with M3S is energetically preferred with the highest free energy barrier of 25.0 kcal mol(−1). In comparison, the cyclization of M3T requires much higher activation free energies (ΔG(≠) = 34.4–57.8 kcal mol(−1)). At the experimental temperature 110 °C, only the linearly-fused cis–trans and cis–syn pathways associated with M3T (ΔG(≠) = 34.4 and 35.5 kcal mol(−1) respectively) are possible. The calculated results also indicate that for both M3S and M3T, the linearly-fused cis–trans triquinane should be the main product, which is consistent with the experimental observation. At last, conformational and NBO analyses on key transition states identified the cis–trans stereocontrol factors. Further calculations indicate that the methyl substituent on the allene group of the reactant substrate improves the stereoselectivity of the reaction but does not affect the rate-determining step.

Palladium-Catalyzed Meta-Selective C–H Bond Activation with a Nitrile-Containing Template: Computational Study on Mechanism and Origins of Selectivity

Density functional theory investigations have elucidated the mechanism and origins of meta-regioselectivity of Pd(II)-catalyzed C-H olefinations of toluene derivatives that employ a nitrile-containing template. The reaction proceeds through four major steps: C-H activation, alkene insertion, β-hydride elimination, and reductive elimination. The C-H activation step, which proceeds via a concerted metalation-deprotonation (CMD) pathway, is found to be the rate- and regioselectivity-determining step. For the crucial C-H activation, four possible active catalytic species-monomeric Pd(OAc)2, dimeric Pd2(OAc)4, heterodimeric PdAg(OAc)3, and trimeric Pd3(OAc)6-have been investigated. The computations indicated that the C-H activation with the nitrile-containing template occurs via a Pd-Ag heterodimeric transition state. The nitrile directing group coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in the transition state, leading to the observed high meta-selectivity. The Pd2(OAc)4 dimeric mechanism also leads to the meta-C-H activation product but with higher activation energies than the Pd-Ag heterodimeric mechanism. The Pd monomeric and trimeric mechanisms require much higher activation free energies and are predicted to give ortho products. Structural and distortion energy analysis of the transition states revealed significant effects of distortions of the template on mechanism and regioselectivity, which provided hints for further developments of new templates.

The conversion of protonated cytosine-SO3− to uracil-SO3−: Insights into the novel induced hydrolytic deamination through bisulfite catalysis

The induced ability of bisulfite to facilitate the hydrolytic deamination of the protonated cytosine-SO3(-) has been studied at the MP2/6-311++G(3df,3pd)//B3LYP/6-311++G(d,p) level and CBS-QB3 approach, respectively. In the gas phase, two distinct groups of mechanisms were explored, the direct hydrolytic deamination (path A) and HSO3(-)-induced hydrolytic deamination (paths B-D), and it indicates that the direct hydrolytic deamination of protonated cytosine-SO3(-) (path A) is unlikely because of the high activation free energy involved in the rate-limiting step, whereas the presence of bisulfite (paths B-D) significantly contributes to decreasing the activation free energy. In the aqueous phase, although the solvent effects of water significantly decrease the activation free energy of path A, the direct hydrolysis reaction remains unfavorable and the HSO3(-)-induced mechanism is still more favorable, which is in agreement with previous experimental data. The pseudo-first-order rate constant (k') for direct hydrolysis is obviously smaller than that of HSO3(-)-induced hydrolytic deamination, which is the most plausible mechanism, where the calculated the k' (1.99-3.81 × 10(-5) s(-1)) is in close proximity to the experimentally determined the pseudo-first-order rate constant (26.2 × 10(-5) s(-1)). Furthermore, the results also manifest that there is a positive correlation between the k' and temperature, and the ratio of reaction rates between direct hydrolysis reaction and HSO3(-)-induced hydrolytic deamination increases with the increase of the bisulfite concentration at a given temperature.

Effects of Protonation and C5 Methylation on the Electrophilic Addition Reaction of Cytosine: A Computational Study

The mechanism for the effects of protonation and C5 methylation on the electrophilic addition reaction of Cyt has been explored by means of CBS-QB3 and CBS-QB3/PCM methods. In the gas phase, three paths, two protonated paths (N3 and O2 protonated paths B and C) as well as one neutral path (path A), were mainly discussed, and the calculated results indicate that the reaction of the HSO(3)(-) group with neutral Cyt is unlikely because of its high activation free energy, whereas O2-protonated path (path C) is the most likely to occur. In the aqueous phase, path B is the most feasible mechanism to account for the fact that the activation free energy of path B decreases compared with the corresponding path in the gas phase, whereas those of paths A and C increase. The main striking results are that the HSO(3)(-) group directly interacts with the C5═C6 bond rather than the N3═C4 bond and that the C5 methylation, compared with Cyt, by decreasing values of global electrophilicity index manifests that C5 methylation forms are less electrophilic power as well as by decreasing values of NPA charges on C5 site of the intermediates make the trend of addition reaction weaken, which is in agreement with the experimental observation that the rate of 5-MeCyt reaction is approximately 2 orders of magnitude slower than that of Cyt in the presence of bisulfite. Apart from cis and trans isomers, the rare third isomer where both the CH(3) and SO(3) occupy axial positions has been first found in the reactions of neutral and protonated 5-MeCyt with the HSO(3)(-) group. Furthermore, the transformation of the third isomer from the cis isomer can occur easily.

Reaction Mechanism of 2-Propynyl-Aniline with Propyne

The reaction mechanism of 2-propynyl-aniline with propyne catalyzed by AuCl3 has been studied by the B3PW91 method with the LANL2DZ effective core potential and basis set for gold, and 6-31G* and 6-311++G** basis set for C,H,O,Cl. The calculated results show that the reaction occurred through eight steps. The hydrogen migration step with the highest activation free energy of 198.13 kJ/mol is the rate determining step. The catalyst is easy to detach from the product with an activation of free energy of 48.83 kJ/mol. In addition, although the reaction has a relative high activation free energy, it can smoothly yield the indole derivatives because it is a strong exothermic reaction of 418.60 kJ/mol.

Computational insights into the photochemical step of the reaction catalyzed by protochlorophylide oxidoreductase

AbstractThe light‐dependent enzyme protochlorophyllide oxidoreductase (EC:1.3.1.33) catalyzes the conversion of protochlorophyllide (PChlide) into chlorophyllide during chlorophyll synthesis. The reaction has been proposed to proceed through light‐induced weakening of the C17–C18 double bond in PChlide, which then facilitates hydride transfer from a NADPH cosubstrate molecule. We have performed DFT and TDDFT computations on the reaction mechanism of this interesting enzyme. The results show that whereas in the ground state the reaction is strongly endergonic and has a very high activation free energy (38 kcal/mol), the first four excited states (corresponding to excitations within the conjugated porphyrin π‐system) afford much lower activation free energies (<25 kcal/mol) and spontaneous (or only slightly endergonic) reaction paths. The sharp shape of the potential energy surface along the reaction coordinate in these excited states allows hydrogen tunneling to occur efficiently on the first few excited state surface, lowering the barrier to values closer to experiment, in agreement with recent suggestions. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

Natural Selection for Kinetic Stability Is a Likely Origin of Correlations between Mutational Effects on Protein Energetics and Frequencies of Amino Acid Occurrences in Sequence Alignments

It appears plausible that natural selection constrains, to some extent at least, the stability in many natural proteins. If, during protein evolution, stability fluctuates within a comparatively narrow range, then mutations are expected to be fixed with frequencies that reflect mutational effects on stability. Indeed, we recently reported a robust correlation between the effect of 27 conservative mutations on the thermodynamic stability (unfolding free energy) of Escherichia coli thioredoxin and the frequencies of residues occurrences in sequence alignments. We show here that this correlation likely implies a lower limit to thermodynamic stability of only a few kJ/mol below the unfolding free energy of the wild-type (WT) protein. We suggest, therefore, that the correlation does not reflect natural selection of thermodynamic stability by itself, but of some other factor which is linked to thermodynamic stability for the mutations under study. We propose that this other factor is the kinetic stability of thioredoxin in vivo, since( i) kinetic stability relates to irreversible denaturation, (ii) the rate of irreversible denaturation in a crowded cellular environment (or in a harsh extracellular environment) is probably determined by the rate of unfolding, and (iii) the half-life for unfolding changes in an exponential manner with activation free energy and, consequently, comparatively small free energy effects can have deleterious consequences for kinetic stability. This proposal is supported by the results of a kinetic study of the WT form and the 27 single-mutant variants of E. coli thioredoxin based on the global analyses of chevron plots and equilibrium unfolding profiles determined from double-jump unfolding assays. This kinetic study suggests, furthermore, one of the factors that may contribute to the high activation free energy for unfolding in thioredoxin (required for kinetic stability), namely the energetic optimization of native-state residue environments in regions, which become disrupted in the transition state for unfolding.

Two Trans and Two Cis Isomers in Caprylolactam in Mixed Solvent of Methanol and Water

Abstract In 13C NMR spectra, four signals of two trans and two cis conformers in caprylolactam were found in a mixed solvent of water and methanol. NMR line broadenings and coalescent phenomena in two conformers occurred at higher temperatures, giving high activation free energy (ΔG‡) for the isomerizations between two trans and cis conformers. ΔG‡ are greatly influenced by the mixed ratio between water and methanol.

Nucleophilicity in ionic liquids. 3. Anion effects on halide nucleophilicity in a series of 1-butyl-3-methylimidazolium ionic liquids.

We have continued the study of halide nucleophilicity in ionic liquids, concentrating on the effect of changing the anion ([BF(4)](-), [PF(6)](-), [SbF(6)](-), [OTf](-), and [N(Tf)(2)](-)) when the cation is [bmim](+) (where bmim = 1-butyl-3-methylimidazolium). It was found that the nucleophilicities of all the halides were lower in all of the ionic liquids than in dichloromethane. Changing the anion affected the order of halide nucleophilicity, e.g., in [bmim][BF(4)] the order of nucleophilicity was Cl(-)>Br(-)>I(-) while in [bmim][N(Tf)(2)] the order was Cl(-)<Br(-)<I(-). It was also found that the nucleophilicity of each halide was different in each ionic liquid, with chloride being almost four times as nucleophilic in [bmim][BF(4)] as in [bmim][SbF(6)]. Similarly bromide was more than four times as nucleophilic in [bmim][BF(4)] as in [bmim][PF(6)]. The activation parameters DeltaG++, DeltaH++, and DeltaS++ have been measured for the reaction of chloride in each of the ionic liquids, plus the reaction of bromide in [bmim][BF(4)] and [bmim][PF(6)]. These data were also compared to each other as well as to a similar reaction in dichloromethane (where these parameters have been estimated for both the free ion and the ion-pair). These studies show that the reaction in the ionic liquids has a high activation free energy barrier, due to the solvent-solute interactions within the ionic liquids. These interactions are described and discussed.

Theoretical and experimental investigation of the formation of E- and Z-Aldimines from the reaction of methylamine with acetaldehyde

The reaction of methylamine with acetaldehyde in pentane at 230 K leads to formation of both E- and Z- aldimines, the Z-isomer being the main product and generated upon kinetic control. The E- form is more stable than the Z- form by 3.3 kcal/mol (DG*). Ab initio calculations have indicated that a tetrahedral zwitterion intermediate is not formed, and the bimolecular process, forming the aminoalcohol intermediate, occurs through a four center transition state, with concerted formation of C-N bond and proton transfer. However, the predicted DG*¹ is very high, indicating that the true mechanism for this step is not bimolecular. A catalyzed pathway must be actuating. The following step, unimolecular elimination of water, also presents a very high activation free energy. Similarly, a catalyzed mechanism is needed. The isomerization from the Z- form to the E- form through inversion of the nitrogen atom has a predicted DG*¹ of 27.0 kcal/mol at 298.15 K, resulting in a lifetime of four months for the Z-isomer.

Simulation of the electron transfer process Cu2+ + Cu+ ⇌ Cu+ + Cu2+ in aqueous solution

A Monte Carlo simulation is performed to investigate the role of solvent in the Cu 2+ Cu + electron exchange process in water. This study is based on the classical Marcus model using the energy gap between the reactant and product states as the reaction coordinate. Since the process has a rather high activation free energy, conventional simulations are not best suited to its complete description, and thus special sampling techniques are required. In this case, a mapping potential is used to drive the system from the reactants to the transition state, and free energies are computed by thermodynamic perturbation and thermodynamic integration methods. A comparison is made between the results obtained by both methods and conclusions are drawn concerning the applicability of the Marcus model to this kind of process.