Intrinsic Reaction Coordinate Research Articles

A QM/QTAIM detailed look at the Watson–Crick↔wobble tautomeric transformations of the 2-aminopurine·pyrimidine mispairs

This work is devoted to the careful QM/QTAIM analysis of the evolution of the basic physico-chemical parameters along the intrinsic reaction coordinate (IRC) of the biologically important 2AP·T(WC)↔2AP·T*(w) and 2AP·C*(WC)↔2AP·C(w) Watson–Crick(WC)↔wobble(w) tautomeric transformations obtained at each point of the IRC using original authors’ methodology. Established profiles reflect the high similarity between the courses of these processes. Basing on the scrupulous analysis of the profiles of their geometric and electron-topological parameters, it was established that the dipole-active WC↔w tautomerizations of the Watson–Crick-like 2AP·T(WC)/2AP·C*(WC) mispairs, stabilized by the two classical N3H⋯N1, N2H⋯O2 and one weak C6H⋯O4/N4 H-bonds, into the wobble 2AP·T*(w)/2AP·C(w) base pairs, respectively, joined by the two classical N2H⋯N3 and O4/N4H⋯N1 H-bonds, proceed via the concerted stepwise mechanism through the sequential intrapair proton transfer and subsequent large-scale shifting of the bases relative each other, through the planar, highly stable, zwitterionic transition states stabilized by the participation of the four H-bonds – N1+H⋯O4–/N4–, N1+H⋯N3–, N2+H⋯N3–, and N2+H⋯O2–. Moreover, it was found out that the 2AP·T(WC)↔2AP·T*(w)/2AP·C*(WC)↔2AP·C(w) tautomerization reactions occur non-dissociatively and are accompanied by the consequent replacement of the 10 unique patterns of the specific intermolecular interactions along the IRC. Obtained data are of paramount importance in view of their possible application for the control and management of the proton transfer, e.g. by external electric or laser fields.

On the Accessible Reaction Channels of Vinyl Gold(I) Species: π- and σ-Pathways.

The potential of vinyl Au species to react either through a controlled π- or σ-pathway is demonstrated. This nomenclature is directly derived from the orbitals of the vinyl Au species leading to the newly formed bonds. When the π-bond of the vinyl Au intermediate is transformed into a σ-bond, we name it π-pathway, and a σ- to σ- transformation is named σ-pathway. Examples of reactions following these pathways are a Au-catalysed [3,3]-sigmatropic rearrangement and a protodeauration reaction. These reactions have been studied using intrinsic bond orbitals (IBOs) and allow for the clear identification of these pathways. Energies for the reaction path of the Au-catalysed [3,3]-sigmatropic rearrangement were in addition computed using CCSD(T)-F12. Analysis of the intrinsic reaction coordinate (IRC) of the [3,3]-sigmatropic rearrangement using IBOs further allows us to refine the previous mechanistic proposal and identifies a hidden intermediate along the reaction path.

Mechanistic elucidation of the origins of the hydrogen-abstraction reactivity of hydroxyimide organocatalysts and its application in catalyst design

The mechanistic origin of the hydrogen-abstraction reactivity of hydroxyimide organocatalysts in three types has been theoretically explored by intrinsic reaction coordinate and distortion/interaction model. All these H-abstraction processes can be divided into two parts: CH bond approaching to catalyst and subsequent breaking via a cross-point structure. Generally, the H-abstraction reactivity increase when a catalyst has small LUMOcatalyst-HOMOsubstrate gap, CH bond approaching energy and distortion energy required to achieve its transition state (TS) geometry, and large electron affinity. The TS structures for 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and N-methyl benzohydroxamic acid (NMBHA) are inclined to be product-like, but much reactant-like for N-hydroxyphthalimide (NHPI)-type catalysts.

A theoretical investigation on the regioselectivity of the [3+2] cycloaddition of nitrile oxide and N-vinylpyrrole

Theoretical calculations were performed on the [3+2] cycloaddition (32CA) reaction of nitrile oxide and N-vinylpyrrole. The regiochemistry of the reaction has been studied based on potential energy surface analysis and global and local reactivity indices of the reactants. The global electron density transfer (GEDT) calculations at the possible transition states revealed that this cycloaddition has a nearly non-polar character. The ELF topological analyses of the selected structures involved in the intrinsic reaction coordinate (IRC) of TS1a suggests that this 32CA reaction takes place through a two-stage one-step mechanism.

A QM/MM study on the enzymatic inactivation of cefotaxime.

The reaction between the antibiotic cefotaxime and the CTX-M-14 class A serine hydrolase is addressed from a theoretical point of view, by means of hybrid quantum mechanics/molecular mechanical (QM/MM) calculations, adopting a new approach that postulates that the residue Ser70 itself should play the role of the acid-base species required for the cefotaxime acylation. The proposed mechanism differs from earlier proposals existing in literature for other class A β-lactamases. The results confirm the hypothesis, and show that the reaction should occur via a concerted mechanism in which the acylation of the lactam carbonyl carbon, protonation of the N7 lactam atom, and opening of the β-lactam ring occurs simultaneously. Exploration of the potential energy surface shows three critical points, associated with reactants, transition state and product. The transition state is characterized by frequency, intrinsic reaction coordinate, atomic charge, and bond orders calculations. The calculated activation barrier is 20kcalmol-1, and the reaction appears to be slightly endothermic by about 12kcalmol-1. We conclude that this approach is feasible, and should be considered as an alternative mechanism or may exist in competition with others already published in the literature. This information should be useful for the design of novel antibiotics and β-lactamase inhibitors. Graphical abstract Three-dimensional view of the potential energy surface of cefotaxime.

Single step mechanism for nucleophilic substitution of 2,3-dichloro naphthoquinone using nitrogen, oxygen and sulfur nucleophiles: A DFT approach

The reactivity of 2,3-dichoro-1,4-naphthoquinone with difunctional nucleophiles (2-mercaptoethanol, 1,2-ethanedithiol, 2-aminoethanol and ethylene glycol) was investigated in mild conditions. Using DFT calculations (B3LYP/6–31++G(d,p) and M11/6–31++G(d,p)), we identified intramolecular interactions in the 2-(substituted)-3-chloro-1,4-naphthoquinone derivatives, which modify the electrophilicity and reactivity of the monosubstituted species, allowing the occurrence of a second nucleophilic attack. Formation of intramolecular hydrogen bonds between the terminal group of the substituent chain and the carbonyl group in the naphthoquinone increases the electrophilicity of the substitution sites of the quinone core, resulting in lower energy barriers for this process. Furthermore, transition state structures and Intrinsic Reaction Coordinate (IRC) calculations showed that the substitution reactions may occur in a single step process, without a tetrahedral intermediate.

Isoconversional approach for non-isothermal decomposition of un-irradiated and photon-irradiated 5-fluorouracil

Kinetic analysis for the non-isothermal decomposition of un-irradiated and photon-beam-irradiated 5-fluorouracil (5-FU) as anti-cancer drug, was carried out in static air. Thermal decomposition of 5-FU proceeds in two steps. One minor step in the temperature range of (270–283°C) followed by the major step in the temperature range of (285–360°C). The non-isothermal data for un-irradiated and photon-irradiated 5-FU were analyzed using linear (Tang) and non-linear (Vyazovkin) isoconversional methods. The results of the application of these free models on the present kinetic data showed quite a dependence of the activation energy on the extent of conversion. For un-irradiated 5-FU, the non-isothermal data analysis indicates that the decomposition is generally described by A3 and A4 modeles for the minor and major decomposition steps, respectively. For a photon-irradiated sample of 5-FU with total absorbed dose of 10Gy, the decomposition is controlled by A2 model throughout the coversion range. The activation energies calculated in case of photon-irradiated 5-FU were found to be lower compared to the values obtained from the thermal decomposition of the un-irradiated sample probably due to the formation of additional nucleation sites created by a photon-irradiation.The decomposition path was investigated by intrinsic reaction coordinate (IRC) at the B3LYP/6-311++G(d,p) level of DFT. Two transition states were involved in the process by homolytic rupture of NH bond and ring secession, respectively.

The role of Li+ ions in the gas phase dehydrohalogenation and dehydration reactions of i-C3H7Br and i-C3H7OH molecules studied by radiofrequency-guided ion beam techniques and ab initio methods.

Gas phase reactive collisions between lithium ions and i-C3H7X (X = Br, OH) molecules have been studied under single collision conditions in the center of mass (CM) 0.01-10.00 eV energy range using a radiofrequency-guided ion beam apparatus. Mass spectrometry analysis of the products did show the presence of [C3H6-Li]+, [HX-Li]+, C3H7+, and C2H3+ as well as of the [Li-i-C3H7Br]+ adduct while [Li-i-C3H7OH]+ was hardly detected. For all these reactive processes, the corresponding cross sections have been measured in absolute units as a function of the CM collision energy. Quantum chemistry ab initio calculations done at the second order Möller Plesset level have provided relevant information on the topology of the potential energy surfaces (PESs) where a reaction takes place allowing the characterization of the stationary points on the respective PESs along their reaction pathways. The connectivity of the different stationary points localized on the PESs was ensured by using the intrinsic reaction coordinate (IRC) method, confirming the adiabatic character of the reactions. The main topology features of the reactive PESs, in the absence of dynamical calculations, were used to interpret at the qualitative level the behavior of the experimental excitations functions, evidencing the role played by the potential energy barriers on the experimental dynamics of the reactions. Reaction rate constants at 303.2 K for different reactions have been calculated from measured excitation functions.

Perspective: chemical dynamics simulations of non-statistical reaction dynamics.

Non-statistical chemical dynamics are exemplified by disagreements with the transition state (TS), RRKM and phase space theories of chemical kinetics and dynamics. The intrinsic reaction coordinate (IRC) is often used for the former two theories, and non-statistical dynamics arising from non-IRC dynamics are often important. In this perspective, non-statistical dynamics are discussed for chemical reactions, with results primarily obtained from chemical dynamics simulations and to a lesser extent from experiment. The non-statistical dynamical properties discussed are: post-TS dynamics, including potential energy surface bifurcations, product energy partitioning in unimolecular dissociation and avoiding exit-channel potential energy minima; non-RRKM unimolecular decomposition; non-IRC dynamics; direct mechanisms for bimolecular reactions with pre- and/or post-reaction potential energy minima; non-TS theory barrier recrossings; and roaming dynamics.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.

Mechanism and Kinetics of Methane Combustion, Part I: Thermal Rate Constants for Hydrogen-Abstraction Reaction of CH4 + O(3P).

The mechanism and kinetics of gas-phase hydrogen-abstraction by the O(3P) from methane are investigated using ab initio calculations and dynamical methods. Not only are the electronic structure properties including the optimized geometries, relative energies, and vibrational frequencies of all the stationary points obtained from state-averaged complete active space self-consistent field calculations, but also the single-point energies for all points on the intrinsic reaction coordinate are evaluated using the internally contracted multireference configuration interaction approach with modified optimized cc-pCVDZ basis sets. Our calculations give a fairly accurate description of the regions around the 3A″ transition state in the O(3P) attacking a near-collinear H-CH3 direction with a barrier height of 12.53 kcal/mol, which is lower than those reported before. Subsequently, thermal rate constants for this hydrogen-abstraction are calculated using the canonical unified statistical theory method with the temperature ranging from 298 K to 1000 K. These calculated rate constants are in agreement with experiments. The present work reveals the reaction mechanism of hydrogen-abstraction by the O(3P) from methane, and it is helpful for the understanding of methane combustion.

CO2 absorption into aqueous solutions of monoethanolamine, piperazine and their blends: Quantum mechanics and molecular dynamics studies

The reaction mechanism and physico-chemical properties of CO2 absorption into aqueous solution of piperazine (PZ), monoethanolamine (MEA) and their blend have been determined by applying (SMD/IEF-PCM) as a solvation model in density functional theory (DFT) calculations and molecular dynamic simulations. Possible absorption pathways were investigated by transition state optimization and intrinsic reaction coordinate (IRC) calculations in the aqueous solution. In the absorption process the low activation energy evaluated for the zwitterion formation specifies this step as a rate determining and indicates the rate activator property of the PZ where PZ-monocarbamate anion is formed easily by zwitterion deprotonation with PZ and MEA as the bases, and decomposes in two path ways: (1) by an inverse reaction of zwitterion deprotonation (2) by a two-step zwitterion mechanism which includes PZ-monocarbamate anion zwitterion intermediate formation and then following by base catalyzed deprotonation of zwitterion. The final products of CO2 absorption process are the anions bicarbonate and PZ-monocarbamate which, according to the obtained results, can be considered respectively favorable from thermodynamics and kinetics aspects.The molecular dynamics results shows that the presence of low concentration of PZ in MEA aqueous solution enhances the CO2 diffusivity and solubility in a 30wt% aqueous amine solution. Consequently, PZ activated MEA aqueous solution can be used as an efficient amine solvent for CO2 absorption.

Hydrogen atom abstraction from Piperazine by hydroxyl radical: a theoretical investigation

ABSTRACTDual level of quantum mechanical calculations have been carried out for hydrogen abstraction from Piperazine [HN(CH2CH2)2NH] initiated by OH radical. Geometry optimisation and frequency calculations of all species involved in the titled reaction have been performed at M06-2X/6-31+G(d,p) level of theory. For the accuracy in the thermochemistry and kinetics data, single-point energy calculations have been further carried out at coupled cluster CCSD(T) method along with 6-311G(d,p) basis set. An energy profile diagram for the reaction has been plotted along with pre-reactive and post-reactive complexes at entrance and exit channels. Intrinsic reaction coordinates (IRCs) calculations have been performed for identification of real transition states that connect it via reactant to product. Our result shows that the H-atom abstraction takes place from the C–H position of Piperazine. The rate constant is calculated using canonical transition state theory (CTST) is found to be 2.86 × 10−10 cm3 molecule−1 s−1 which is in good agreement with the reported experimental rate constant (2.38 ± 0.28) × 10−10 cm3 molecule−1 s−1 at 298 K. We have also reported rate constant for the temperature range 300–500 K. Using group-balance isodesmic reaction, the standard enthalpies of formation for Piperazine and product radicals generated by hydrogen abstraction are reported. The branching ratios for both reaction channel (i.e. H-abstraction from –CH2 and –NH position of Piperazine) are found to be 93% and 7%, respectively. The calculated atmospheric life time of Piperazine is found to be 0.97 hour.

Hydrogen generation from water molecule with Pt7 clusters

The reaction paths of hydrogen generation from water molecule with Pt7 cluster are presented, based on the density functional theory with the generalized gradient approximation. The 12 stable complex structures of the H2O@Pt7 reactants and the corresponding structures of the H2 + O@Pt7 and H + HO@Pt7 products are optimized for various adsorption sites on the cluster. The frequency analysis has been used to confirm the energy stability of the structures. The geometries of the transition states and the intrinsic reaction coordinates are calculated at the same theoretical level. The energy barrier for each reaction is determined. The results demonstrated that Pt7 cluster can abstract H or H2 from H2O molecule depend on the initial structures of reactant and the active energy. These results are helpful for designing the practical hydrogen generation scheme with these reactions.

A density functional theory study of double proton transfer reactions in formamide, formamide-formic acid and formic acid dimers

We have performed a theoretical study on the double proton transfer (DPT) reactions for the formamide-formamide, formamide-formic acid and formic acid-formic acid dimeric complexes by using the ωB97XD/aug-cc-pVDZ level of density functional theory (DFT). The DFT calculated reaction energy barriers are calibrated by the high-level MP2 and CCSD(T) methods at the complete basis set limit. The reaction energy profiles along the intrinsic reaction coordinates have been analyzed using the symmetry adapted perturbation theory. The reaction mechanism is elucidated by examining the reaction force, the chemical potential and the reaction electronic flux. Our results show that the DPT reactions are essentially synchronous which can form an alternative reaction pathway to monomer tautomerization. The reactions proceed with significant intermolecular bond shortening and charge accumulation, yielding large increment in the exchange energy toward the formation of the reaction energy barrier. Once the transition state is reached, the energetic constraint is released by the attractive energies.

Theoretical study of OCCHCN as a potential alternative insulation gas for SF6

Cyanoketene (OCCHCN) has been reported as a potential alternative insulation gas for SF6 in Patent US0135817. Stationary point equilibrium geometries on the ground state have been optimized at the B3LYP/6-311+G(d,p) level, and the harmonic vibration frequencies are calculated at the same level. The HOMO-LUMO energy gaps (Eg), ionization potentials (IP), and electron affinities (EA) of the studied molecules are obtained. The minimum energy path (MEP) is obtained by the intrinsic reaction coordinate (IRC) theory, and the energetic information is further refined by QCISD(T) (single-point) method. The results show that OCCHCN can be used as SF6 alternative insulation gas in high voltage equipment according to potential energy surface analysis. As the isomerization and the cleavage reactions potential barriers are lower than the Eg and IP values, resulting in OCCHCN is not easy to be ionized and excited.

Two New Methods To Generate Internal Coordinates for Molecular Wave Packet Dynamics in Reduced Dimensions.

The curse of dimensionality still remains as the central challenge of molecular quantum dynamical calculations. Either compromises on the accuracy of the potential landscape have to be made or methods must be used that reduce the dimensionality of the configuration space of molecular systems to a low dimensional one. For dynamic approaches such as grid-based wave packet dynamics that are confined to a small number of degrees of freedom this dimensionality reduction can become a major part of the overall problem. A common strategy to reduce the configuration space is by selection of a set of internal coordinates using chemical intuition. We devised two methods that increase the degree of automation of the dimensionality reduction as well as replace chemical intuition by more quantifiable criteria. Both methods reduce the dimensionality linearly and use the intrinsic reaction coordinate as guidance. The first one solely relies on the intrinsic reaction coordinate (IRC), whereas the second one uses semiclassical trajectories to identify the important degrees of freedom.

Theoretical studies on the hydrogen abstraction reactions of methyl esters with HO2radical and the following β-scission reactions

Unsaturated fatty acid methyl esters are ubiquitous in biodiesel fuels. The C = C double bond greatly affects the combustion characteristics of biodiesel, especially its ignition behavior at low temperatures. In this work, we report detailed theoretical study on the mechanism and kinetics of the hydrogen abstraction reactions of linear unsaturated C6 methyl esters with hydroperoxy radical (HO2), which play a critical role in the low-temperature combustion of biodiesel. Reaction profiles are obtained via intrinsic reaction coordinate (IRC) analysis including the formation of reactant complexes and product complexes at the entrance and exit channels, respectively. The potential energy surfaces are explored at the CBS-QB3 level. The following β-scission reactions of the forming radicals are also investigated at the same level of theory. The high-pressure limit rate constants for all the reactions in the temperature range from 500 to 2000 K are calculated via conventional transition-state theory with quantum tunneling effect and fitted to the modified Arrhenius expression.

Revisiting the Dielectric Constant Effect on the Nucleophile and Leaving Group of Prototypical Backside SN2 Reactions: A Reaction Force and Atomic Contribution Analysis.

The solvent effect on the nucleophile and leaving group atoms of the prototypical F- + CH3Cl → CH3F + Cl- backside bimolecular nucleophilic substitution reaction (SN2) is analyzed employing the reaction force and the atomic contributions methods on the intrinsic reaction coordinate (IRC). Solvent effects were accounted for using the polarizable continuum solvent model. Calculations were performed employing 11 dielectric constants, ε, ranging from 1.0 to 78.5, to cover a wide spectrum of solvents. The reaction force data reveal that the solvent mainly influences the region of the IRC preceding the energy barrier, where the structural rearrangement to reach the transition state occurs. A detailed analysis of the atomic role in the reaction as a function of ε reveals that the nucleophile and the carbon atom are the ones that contribute the most to the energy barrier. In addition, we investigated the effect of the choice of nucleophile and leaving group on the ΔE0 and ΔE‡ of Y- + CH3X → YCH3 + X- (X, Y = F, Cl, Br, I) in aqueous solution. Our analysis allowed us to find relationships between the atomic contributions to the activation energy and leaving group ability and nucleophilicity.

Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1C4 and 4C1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4C1 conformations; that is, the potential energy of the global minimum of 4C1 is lower than that of 1C4 (thermodynamic predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance).

Study of adsorption and dissociation pathway of H2 molecule on MgnRh (n = 1–10) clusters: A first principle investigation

We report the interaction of hydrogen molecule with MgnRh clusters using density functional formalism with an objective to study (a) the reactivity of small sized MgnRh clusters with H2 molecule and (b) the catalytic effect of Rh on the Mgn cluster for adsorption and dissociation of hydrogen. From the variation of thermodynamic parameters, adsorption and chemisorption etc. with the size of the cluster, we found that the most stable lowest energy structure in the series is Mg6Rh, whereas, Mg9Rh is the most effective hydrogen storage cluster. Interaction of H2 with MgnRh cluster shows a significant reduction in the activation barrier energy, which helps in the hydrogen dissociation. The chemisorptions energy reveals that Mg9Rh cluster act as an effective catalytic agent for hydrogen adsorption and dissociation. The calculated activation barrier energy of H2Mg9Rh has been verified by the study of intrinsic reaction coordinates (IRC) pathway between Mg9Rh and H2.