Reactant Complex Research Articles

Aerobic photolysis of methylcobalamin: unraveling the photoreaction mechanism.

The photo-reactivity of cobalamins (Cbls) is influenced by the nature of axial ligands and the cofactor's environment. While the biologically active forms of Cbls with alkyl axial ligands, such as methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), are considered to be photolytically active, in contrast, the non-alkyl Cbls are photostable. In addition to these, the photolytic properties of Cbls can also be modulated in the presence of molecular oxygen, i.e., under aerobic conditions. Herein, the photoreaction of the MeCbl in the presence of oxygen has been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT). The first stage of the aerobic photoreaction is the activation of the Co-C bond and the formation of the ligand field (LF) electronic state through the displacement of axial bonds. Once the photoreaction reaches the LF excited state, three processes can occur: namely the formation of OO-CH3 through the reaction of CH3 with molecular oxygen, de-activation of the {Im⋯[CoII(corrin)]⋯CH3}+ sub-system from the LF electronic state by changing the electronic configuration from (dyz)1(dz2)2 to (dyz)2(dz2)1 and the formation of the deactivation complex (DC) complex via the recombination of OO-CH3 species with the de-excited [CoII(corrin)] system. In the proposed mechanism, the deactivation of the [CoII(corrin)] subsystem may coexist with the formation of OO-CH3, followed by immediate relaxation of the subsystems in the ground state. Moreover, the formation of the OO-CH3 species followed by the formation of the {[CoIII(corrin)]-OO-CH3}+ complex stabilizes the system compared to the reactant complex.

A DFT and MP2 mechanistic and kinetic study on hypohalogenation reaction of cysteine and N-acetylcysteine in aqueous solution

A theoretical study simulating the hypohalogenation reaction of cysteine (CSy) and N-acetylcysteine (NAC) has been performed with the objective of obtaining the energetic, electronic and kinetic properties for the reactions at room temperature and body temperature and considering neutral and basic conditions in aqueous medium. The study has been performed using the M06-HF, M06-2X, MPWB1K, BHANDHLYP density functional methods and with the MP2 method along with either the 6-311+G(d, p) basis set or the extended 6-311++G(3df,3pd) basis set. The results of the study indicate that all reactions proceed through the formation of the reactant complex structure, which is stabilised by the formation of intermolecular hydrogen bond between the reactant species. The reactions are also thermodynamically preferred to take place at room temperature. The reaction involving hypochlorous acid is faster and more thermodynamically preferred to the reaction involving hypochlorite anion, both at room temperature and at body temperature. The relative magnitude for the rate constant involving CSy and NAC is dependent on the pH of the solution. A comparison of the calculation methods utilised for the study suggests that the best methods for estimation of the rate constant are those containing both the HF-like exchange and the kinetic density components.

Local Structural Dynamics at the Metal-Centered Catalytic Site of Polymerases is Critical for Fidelity

The fidelity of DNA polymerases (Pols) refers to their ability to incorporate the correct nucleotide into the growing strand during DNA synthesis. Each Pol operates with a certain degree of fidelity, from high (∼10–8; ∼1 error in 108 bases) to low (∼10–1; ∼1 error in 10 bases) values. The mechanistic factors behind these differences in fidelity are poorly understood. Here, we show that the formation of the Michaelis–Menten complex is critically affected by the metal-mediated dynamics of local structural features at the catalytic center of Pols. We demonstrated this by integrating recent structural and kinetics data of high-fidelity Pol β and low-fidelity Pol η with equilibrium molecular dynamics and free-energy simulations of paired and mispaired reactant complexes of these Pols. We found that local dynamics at the reaction center determines whether the nucleophile is optimally aligned to incorporate the correct (dCTP) or incorrect (dATP) nucleotide opposite a template deoxyguanosine (dG). In Pol β, local structural distortions at the catalytic site are visible only in the dG:dATP mispair complex, which energetically disfavors incorrect nucleotide addition and thus promotes high fidelity. In contrast, in Pol η we observed a more flexible base pair shape complementarity at the catalytic site. This allows reactive configurations of matched and mismatched complexes to be formed with similar ease, thus explaining the low fidelity of Pol η in line with the experimental evidence. Comparisons with other Pols suggest that these local metal-mediated structural dynamics at the reaction center of the catalytic site are crucial to modulating Pol fidelity.

Understanding the structural insights of enzymatic conformations for adenylosuccinate lyase receptor in malarial parasite Plasmodium falciparum

The dreadful disease malaria is one among the infectious diseases that comes in third number after the tuberculosis and HIV. This disease is spread by female Anopheles mosquito and caused by the malarial parasite sp notably Plasmodium falciparum. In this, the organism has several enzymes for processing the infection and growth mechanism and among that, the adenylosuccinate lyase is an enzyme that plays a critical role in metabolism and cellular replication via its action in the de novo purine biosynthetic pathway. Adenylosuccinate has been studied for two reaction mechanisms, and in that, the adenylosuccinate to AMP and fumarate is core important. As of now, there have been several studies indicating the reaction mechanism of adenylosuccinate lyase, this study projects the conformations of the reactant and product changes through molecular docking and molecular dynamic simulations. Adenylosuccinate bound complex involves His role in the product than the reactant complex, and the complex shows high flexibility due to fumarate. Thus, identifying the core inhibitor that binds to His rings could be a standard adenylosuccinate lyase inhibitor, that can block the malarial diseases in humans. In addition to the competitive inhibition site, we also predicted the uncompetitive ligand binding site, which suggest the alternate region to be targeted. Thus, from this work, we suggest both competitive and uncompetitive binding regions for the purpose identifying the malarial inhibitors.

Metabolism of 8-aminoquinoline (8AQ) primaquine via aromatic hydroxylation step mediated by cytochrome P450 enzyme using density functional theory

The 8-aminoquinoline (8AQ) drug Primaquine (PQ) is a prime anti-malarial drug, used in the treatment of malaria due to plasmodium vivax and plasmodium ovale. The hydroxylated metabolite of Primaquine is also responsible for many essential sexual transmission stages of Plasmodium falciparum. Present work reported the hydroxylation of Primaquine at ortho (2PQ) and para (4PQ) position by Cytochrome P450 enzyme. Density functional theory (DFT) is used to investigate the underlying pathway for aromatic hydroxylation at ortho (2PQ) and para (4PQ) position to produce 2-hydroxylated and 4-hydroxylated Primaquine respectively. Truncated model of putative active oxidant i.e. ferryl oxo porphyrin cation radical [FeIV(O)(heme+·)], which is referred as Cpd I in Cytochrome P450 enzymes has been used to mimic the behavior of enzyme. Substrate was modelled and reaction mechanism for two degenerate spin states namely doublet and quartet were performed to dwell the overall potential energy landscape, along with electronic structure and properties of reactant complex (RC), transition states (TS), intermediates (IM) and product complex (PC). The reaction was stepwise with electrophillic addition as the rate determining step, spin selectivity product formation was observed for hydroxylated product formation on high spin (HS) surface. All calculations are done for isolated reaction coordinate.

Theoretical study of the reactions of triplet Oxygen atom with methyl and ethyl hydroperoxides

The O(3P) + CH3OOH and O(3P) + C2H5OOH reactions were characterised using M06-2x/aug-cc-pVQZ level of theory. The electronic energies were refined by CCSD(T)/CBS theory. The H-abstraction channels involving the formation of reactant complexes were more kinetically favourable than others. The H-abstraction from the OH group was dominant channel for the O(3P) + CH3OOH reaction at the temperature less than 1200 K. For the O(3P) + CH3CH2OOH reaction, the dominant channel is the H-abstraction from the OH group over the temperature range of 600–1300 K and the H-abstraction from the CH2 group at the temperature less than 500 K.

Interplay between two degenerate spin state determines the hydroxylation of 4-nitrophenol catalyzed via Cytochrome P450

4-Nitrophenol is formed during the synthesis of paracetamol. It is used in various xenobiotic metabolism processes and other essential biochemical processes. It is metabolized via cytochrome P450 enzyme. The present work reported the hydroxylations of 4-nitrophenol at the ortho position by Cytochrome P450 metalloenzyme. Truncated model of putative active oxidant i.e. ferryl oxo porphyrin cation radical [FeIV(O)(heme+)], referred as Cpd I in cytochrome P450 enzymes has been used to mimic the behavior of enzyme. In the current investigations, 4-nitrophenol (Substrate) is modeled with Cpd I and reaction mechanism for two degenerate spin states named as doublet (LS) and quartet (HS) is performed to dwell the overall potential energy landscape, along with electronic structures and properties of reactant complex (RC), transition states (TS), intermediates (IM) and product complex (PC). The reaction is stepwise with electrophillic addition as the rate determining step, spin selectivity product formation is observed only at high spin (HS) surface. So, the present reaction pathway is single state reactivity (SSR) by forming the suicidal complex at low spin state (LS).

Counterion Effect on the Mechanism of Gold(I)‐Catalyzed Cycloisomerization of 3‐Allenylmethylindoles to 4,9‐Dihydro‐1H‐Carbazoles: A Computational Study

AbstractA detail computational investigation of the mechanism of the title reaction has been carried out with density functional theory (DFT) method to make clear the role of counterion and the regiochemistry of the initial nucleophilic attack of the indole core on the alkylating agent (i. e. C2 vs C3 position). The calculated results suggest that 6‐endo‐trig cyclization followed by bistriflimide counterion‐assisted proton transfer could account for the formation of the final product. In other words, intramolecular nucleophilic attack by C2 of the indole group towards the terminal carbon atom of the allene moiety leads to the formation a 6‐membered ring fused indolyl intermediate, which undergoes deprotonation and protodemetallation to give the final product. Of the three steps, the rate determining step of the whole catalytic cycle is the deprotonation step with an activation free energy of 14.4 kcal/mol. It is also found that the regiochemistry of the initial nucleophilic attack of the indole moiety on the cationic gold‐activated allene moiety is dependent on the conformation of reactant complex, the nature of substituent in the allene moiety and the size of phosphine ligand.

Kinetics study on the reactions of dimethyl ether with triplet oxygen and hydrogen atoms

The reaction kinetics of dimethyl ether (CH3OCH3) with O(3P) and hydrogen atom have been studied. Electronic energies were calculated by single-point energy calculations at the CCSD(T)/cc-PVnZ (n = D, T, Q) levels. Rate coefficients of the reactions were calculated by the canonical variational transition state theory (CVT) with the small curvature tunneling (SCT) correction. The hydrogen-abstraction channels involve the formation of reactant complexes in the entrance channels and show positive temperature dependence. Their branching rates are almost 1.0 at the temperature less than 1000 K.

Reply to Comment on "Using NMR to Test Molecular Mobility during a Chemical Reaction".

Reports of boosted diffusion during chemical and enzymatic reactions have inspired a loyal community of scientists who find them so counterintuitive that they must be artifact. This second Comment on the subject by these authors is about technicalities of how to analyze data we deposited online regarding J. Phys. Chem. Lett. 2021 12, 2370 and Science 2020 369, 537. Now that their own data is also online, one apparent discrepancy can be resolved: we demonstrate that the authors' data agrees with ours because their first Comment on this subject reported only truncated short-time excerpts of the longer time series they deposited online (zenodo.org/record/4628353). This second Comment adds five additional objections, four of which are too technical to change the qualitative conclusion. The fifth objection errs because it omits recognizing intermediate states of the click reaction during which one reactant complexes with the catalyst to form an object of larger size. Elsewhere we analyzed in great detail the respective influences of boosted diffusion and this hydrodynamic effect (DOI: 10.26434/chemrxiv.14740563.v1). The factual evidence and reasoning in this Reply strongly support this laboratory's earlier conclusions regarding boosted diffusion during common chemical reactions.

Multistructural Variational Reaction Kinetics of the Simplest Unsaturated Methyl Ester: H-Abstraction from Methyl Acrylate by H, OH, CH3, and HO2 Radicals.

The H-abstraction reaction kinetics of methyl acrylate (MA) + H/OH/CH3/HO2 radicals have been investigated theoretically in the present work. For these reactions, the reaction energies and barrier heights are first computed using several density functionals and compared to the coupled cluster CCSD(T)-F12/jun-cc-pVTZ benchmark calculations. The M062X/maug-cc-pVTZ method shows the best performance with the smallest mean unsigned deviation (MUD) of 0.42 kcal mol-1. Combined with the electronic structure calculations using the M062X/maug-cc-pVTZ method, the multistructural canonical variational transition-state theory (MS-CVT) with small-curvature tunneling (SCT) is employed to calculate the reaction rate constants at 500-2000 K. The variational effect is between 0.56 and 1.0, the multistructural torsional anharmonicity factor ranges from 0.004 to 4.57, and the tunneling coefficient is in the range of 0.5-4.70. Notably, given the existence of reactant complexes (RCs) between reactants and transition states for the reaction systems MA + OH/HO2, we further compare the rate constants under the low-pressure limit (LPL) kinetic model, which treats the reaction as a single-step process and neglects RCs, and the pre-equilibrium model, which takes RCs into account in the reaction and treats the reaction as a two-step process. The rate constants calculated by these two models are similar within the combustion temperature range, and apparent differences occur at lower temperatures. In addition, we determine the branching ratios as a function of temperature and find that the methyl site (S3) abstractions by OH and H radicals are dominant in the low- and high-temperature ranges, respectively. Moreover, we update the kinetic model with the calculated H-abstraction rate constants to simulate the ignition delay times of MA. The simulations of the updated model are in good agreement with experimental results. The accurate reaction kinetics determined in this work are useful for the understanding and prediction of consumption branching fractions and ignition properties of the unsaturated methyl esters.

Catalytic Descriptors to Investigate Catalytic Power in the Reaction of Haloalkane Dehalogenase Enzyme with 1,2-Dichloroethane.

Enzymes play a fundamental role in many biological processes. We present a theoretical approach to investigate the catalytic power of the haloalkane dehalogenase reaction with 1,2-dichloroethane. By removing the three main active-site residues one by one from haloalkane dehalogenase, we found two reactive descriptors: one descriptor is the distance difference between the breaking bond and the forming bond, and the other is the charge difference between the transition state and the reactant complex. Both descriptors scale linearly with the reactive barriers, with the three-residue case having the smallest barrier and the zero-residue case having the largest. The results demonstrate that, as the number of residues increases, the catalytic power increases. The predicted free energy barriers using the two descriptors of this reaction in water are 23.1 and 24.2 kcal/mol, both larger than the ones with any residues, indicating that the water solvent hinders the reactivity. Both predicted barrier heights agree well with the calculated one at 25.2 kcal/mol using a quantum mechanics and molecular dynamics approach, and also agree well with the experimental result at 26.0 kcal/mol. This study shows that reactive descriptors can also be used to describe and predict the catalytic performance for enzyme catalysis.

Antiferromagnetically coupled [Fe8S9] cluster catalyzed acetylene reduction in a nitrogenase-like enzyme DCCPCh: Insights from QM/MM calculations

QM/MM calculations have been used to elucidate the reaction mechanism of the reduction of acetylene to ethylene catalyzed by a nitrogenase-like enzyme DCCPCh with an unusual [Fe8S9] double-cubane cluster. Various plausible reaction pathways, involving different oxidation states and protonation states of the iron-sulfur cluster, have been analyzed to find the most favorable one. The acetylene substrate bridges to the [Fe8S8] cluster via its triple bond in a μ-(bis-η2) coordination mode. After a proton-coupled electron transfer reduction of the reactant complex, the acetylene reduction may be described to proceed via a special “double-electron transfer induced proton transfer” mechanism, deduced from the principal interacting orbital analysis. The anti-ferromagnetically coupled [Fe8S8] cluster delivers a pair of α- and β-electrons to the substrate, concertedly but asynchronously with a proton transfer mediated by the second-shell Lys147 residue to one of the acetylene carbon atoms. Subsequently, the second proton-coupled electron transfer proceeds, followed by protonation of the substrate to afford the ethylene product. During the two-electron reaction, the oxidation states of the [Fe8S8] cluster cycle from [FeII6FeIII2], to [FeII7FeIII], to [FeII5FeIII3], and back to [FeII6FeIII2].

A theoretical and experimental study on etherification of primary alcohols with the hydroxyl groups of cellulose chain (n = 1–3) in acidic condition

Etherification mechanism of primary alcohols R-CH2OH with the hydroxyl groups of cellulose chain (n = 1–3) in acidic condition were investigated by using density functional theory (DFT) and two-layer ONIOM approach. Geometry and energy of the reactants, products, reactant complexes, product complexes and transition state (TS) structures were optimized and calculated at the B3LYP/6–311 g(d,p) level, ONIOM (B3LYP/6–311 g(d,p):PM3MM) level, and CCSD(T)/6–311+g*//B3LYP/6–311 g(d,p) level. The computational results reveal that the etherification comply with bimolecular nucleophilic substitution (SN2) mechanism; potential energy surface (PES) of the reaction is compatible with the type of cation-molecule reaction; reactants and products can form the stable activated complexes with H+ and water, in this state H+ is occupied by both alcohol and water, or ether and water; substituent R in primary alcohol R-CH2OH (R = H, CH3, CH2CH3, CH2NHCH3, CH2OCH3, CH2N(CH3)3Cl, CH2F) affect significantly on the both energy barrier of activation step and energy barrier of H3O+ releasing step. The combination of calculational data and experimental data were applied to make findings more rigorous.

The conductor‐like polarizable continuum model study of indenyl effect on the ligand substitution reaction in the (η5‐C9H7)Co(CO)2 complex

AbstractIn the present article, utilizing the mPW1PW91 functional, quantum chemical computations were applied to find the impact of indenyl on the ligand substitution reaction in the (η5‐C9H7)Co(CO)2 complex. The solvent impacts were surveyed utilizing the self‐consistent reaction field theory based on the conductor‐like polarizable continuum model. Six aprotic and protic solvents were selected. Co–C and Co–P bond distances changes in the reactant and product complexes were illustrated. The thermodynamic parameters of carbonyl ligand substitution reactions in the (η5‐C5H5)Co(CO)2 and (η5‐C9H7)Co(CO)2 complexes were calculated in the gas and solution phases. Also, rate constant values of these reactions were calculated within 300−1200 K utilizing transition state theory based on the statistical thermodynamics in the gas phase. The computed relative rate constant values (kr) indicated good compatibility with the experimental value in a similar reaction.

Kinetics of the Reactions of Methyl Radical with Hydrogen, Methyl and Ethyl Peroxides

AbstractThe HOOH+CH3, CH3OOH+CH3 and CH3CH2OOH+CH3 reactions were characterized using accurate ab initio methods with reliable basis sets. The reaction rate constants were calculated by canonical variational transition state theory as applied to a complex mechanism involving the formation of reactant complexes. The formation of aldehyde or formaldehyde was observed when the CH3 radical attacks on the CH2 group in CH3CH2OOH or on the CH3 group in CH3OOH. The results showed that the channels of H‐abstraction from OH group are dominant channels at low temperature, while the channels of OH‐transfer to CH3 become predominant with increasing temperature. For the CH3OOH+CH3 reaction, the channel producing CH2O+OH and the OH‐transfer channel have a similar rate coefficient.

Independent, Incidence Independent and Weakly Reversible Decompositions of Chemical Reaction Networks

Chemical reaction networks (CRNs) are directed graphs with reactant or product complexes as vertices, and reactions as arcs. A CRN is weakly reversible if each of its connected components is strongly connected. Weakly reversible networks can be considered as the most important class of reaction networks. Now, the stoichiometric subspace of a network is the linear span of the reaction vectors (i.e., difference between the product and the reactant complexes). A decomposition of a CRN is independent (incidence independent) if the direct sum of the stoichiometric subspaces (incidence maps) of the subnetworks equals the stoichiometric subspace (incidence map) of the whole network. Decompositions can be used to study relationships between positive steady states of the whole system (induced from partitioning the reaction set of the underlying network) and those of its subsystems. In this work, we revisit our novel method of finding independent decomposition, and use it to expand applicability on (vector) components of steady states. We also explore CRNs with embedded deficiency zero independent subnetworks. In addition, we establish a method for finding incidence independent decomposition of a CRN. We determine all the forms of independent and incidence independent decompositions of a network, and provide the number of such decompositions. Lastly, for weakly reversible networks, we determine that incidence independence is a sufficient condition for weak reversibility of a decomposition, and we identify subclasses of weakly reversible networks where any independent decomposition is weakly reversible.

Unraveling the computed non-least motion pathway for the homodimerization of superchameleonic isocyanides: the peculiar nonsymmetrical (F-NC)2 reactant complex.

Isocyanides are commonly qualified as chameleonic compounds because of their reactions with both nucleophiles and electrophiles. In some instances, their chameleonic behavior changes to superchameleonic when they are involved in homodimerization processes, with the two initially identical isocyanide units adopting different roles along the reaction coordinate. We present here a detailed analysis of the computed non-least motion pathway that two isocyanides, the superchameleonic F-NC and, for the sake of comparison, the standard Me-NC, follow when reacting with themselves by comparing the evolution of a series of representative geometrical and electronic parameters along the respective reaction coordinates. This study shows that the two F-NC units are notoriously distinguishable from each other in all the parameters under scrutiny. Furthermore, we envisage that the superchameleonic character of F-NC seems to be most likely due to a minimal electrostatic interaction between the two entities at the earliest stage of the reaction. We also show that MeO-NC, MeS-NC and Me3P[double bond, length as m-dash]N-NC might be postulated as new examples of superchameleonic isocyanides.

Consistent inclusion of continuum solvation in energy decomposition analysis: theory and application to molecular CO2 reduction catalysts.

To facilitate computational investigation of intermolecular interactions in the solution phase, we report the development of ALMO-EDA(solv), a scheme that allows the application of continuum solvent models within the framework of energy decomposition analysis (EDA) based on absolutely localized molecular orbitals (ALMOs). In this scheme, all the quantum mechanical states involved in the variational EDA procedure are computed with the presence of solvent environment so that solvation effects are incorporated in the evaluation of all its energy components. After validation on several model complexes, we employ ALMO-EDA(solv) to investigate substituent effects on two classes of complexes that are related to molecular CO2 reduction catalysis. For [FeTPP(CO2-κC)]2− (TPP = tetraphenylporphyrin), we reveal that two ortho substituents which yield most favorable CO2 binding, –N(CH3)3+ (TMA) and –OH, stabilize the complex via through-structure and through-space mechanisms, respectively. The coulombic interaction between the positively charged TMA group and activated CO2 is found to be largely attenuated by the polar solvent. Furthermore, we also provide computational support for the design strategy of utilizing bulky, flexible ligands to stabilize activated CO2via long-range Coulomb interactions, which creates biomimetic solvent-inaccessible “pockets” in that electrostatics is unscreened. For the reactant and product complexes associated with the electron transfer from the p-terphenyl radical anion to CO2, we demonstrate that the double terminal substitution of p-terphenyl by electron-withdrawing groups considerably strengthens the binding in the product state while moderately weakens that in the reactant state, which are both dominated by the substituent tuning of the electrostatics component. These applications illustrate that this new extension of ALMO-EDA provides a valuable means to unravel the nature of intermolecular interactions and quantify their impacts on chemical reactivity in solution.

Direct dynamics in a proton transfer reaction of isomer product competition. Insight into the suppressed formation of the isoformyl cation.

Proton transfer between HOCO+ and CO produces the formyl cation HCO+ and isoformyl cation HOC+ isomers initiating multiple astrochemical reaction networks. Here, the direct chemical dynamics simulations are performed to uncover the underlying atomistic dynamics of the above reaction. The simulations reproduce the measured product energy and scattering angle distributions and reveal that the reaction proceeds predominantly through a direct stripping mechanism which results in the prominent forward scattering observed in experiments. The reaction dynamics show propensity for the HCO+ product even at a collision energy larger than the threshold for HOC+ formation. This is a consequence of the larger opacity and impact parameter range for HCO+. In accordance with the revealed direct mechanistic feature, the reaction can be controlled by orienting the reactants into a reactive H-C orientation that also favors HCO+ formation. Considering the lack of equilibrated reactant complexes and the on the fly migration of the proton, the CO2-catalyzed isomerization is assumed to have insignificant impact on the isomer ratios. This work provides insights of dynamical effects besides energetics into the interesting finding of strongly suppressed formation of the metastable isoformyl cation for related proton transfer reactions in the measurements.