On the equivalence of direct mechanisms and structurally minimal pathways

A reaction-pathway identification procedure has two distinct phases. The first phase enumerates exhaustively the feasible candidate pathways, and the second phase identifies the ultimate feasible pathway or pathways among them. Probably the most efficient way to execute the first phase is to algorithmically generate the networks of feasible candidate pathways from a predefined set of plausible elementary reactions. The available algorithmic methods for this purpose can be roughly grouped into two major classes, one based on graph theory and the other on linear algebra. Both classes of methods consider any chemical reaction system as a network of elementary reactions, thereby implying that the two classes are interrelated. This paper studies the linear algebraic concept termed direct mechanism introduced in the mid-eighties and the graph-theoretical concept termed structurally minimal pathway introduced two decades later. Herein, it has been formally proven that the two concepts are equivalent.     

Michaelis-Menten relations for complex enzymatic networks

Most biological processes are controlled by complex systems of enzymatic chemical reactions. Although the majority of enzymatic networks have very elaborate structures, there are many experimental observations indicating that some turnover rates still follow a simple Michaelis-Menten relation with a hyperbolic dependence on a substrate concentration. The original Michaelis-Menten mechanism has been derived as a steady-state approximation for a single-pathway enzymatic chain. The validity of this mechanism for many complex enzymatic systems is surprising. To determine general conditions when this relation might be observed in experiments, enzymatic networks consisting of coupled parallel pathways are investigated theoretically. It is found that the Michaelis-Menten equation is satisfied for specific relations between chemical rates, and it also corresponds to a situation with no fluxes between parallel pathways. Our results are illustrated for a simple model. The importance of the Michaelis-Menten relationship and derived criteria for single-molecule experimental studies of enzymatic processes are discussed.     

Autocatalytic and other general networks for chemical mechanisms,pathways, and cycles: Their systematic and topological generation

Methods to generate a priori all the finite number of possible mechanisms of chemical reactions and/or synthetic pathways or thermodynamic cycles, which we represent by general networks, are given for any number of reaction steps or total number of species (reactants, products, catalysts, and intermediates). General networks do not place limitations on the types of species, e.g. intermediates can be short-lived, thereby participating in at most two elementary reaction steps, or longer-lived, participating in more than one way. Step stoichiometric coefficients can be more than unity. Reactants or products may also act as catalysts or inhibitors. Species vertices and the general networks themselves in which they occur are classified topologically. Topological invariants of the networks with respect to the number of reaction steps are found. Mechanisms with desired features, e.g. containing certain numbers of generalized catalysts, chains, autocatalysts, etc., are generated using the invariants, from the simplest prototypes, for successively larger numbers of reaction steps. Special emphasis is given to autocatalytic networks due to their role in chemical oscillations, dynamical instabilities and in selfreplicating reactions. Examples given include the malic acid cycle, oscillatory cycles in glycolysis, Lotka-Volterra-Prigogine-Glansdorff models, and others. Oscillating and/or self-replicating cycles that have been invoked in various contexts are shown to have a common topological feature. The methods are useful also in the many autocatalytic processes of chemical engineering importance.     

A possible construction of a complex chemical reaction network

A procedure is suggested for the construction of chemical reaction networks. We define the kinetic communication as a transfer of atoms or atomic groups between two species and determine all the kinetic communications occurring in the possible mechanism of a complex chemical process. The set of kinetic communications is the basis of the communication matrices resulting in the complete network of the overall reaction.Limiting the consideration for certain types of kinetic communications we obtain the reaction subnetworks and selecting arbitrarily species among those participating in the possible mechanism we introduced the concept of the partial subnetworks which correspond to subsets of the complete network.By the simple analysis of the subnetworks it is easy to obtain the sequence network indicating the pathways via which the selected species are formed in the course of the overall process, by the transfer of chosen atoms or atomic groups.     

MECHGEN: computer aided generation and reduction of reaction mechanisms

The paper describes selection rules implemented in a software generating "possible reaction mechanism", i.e. a set of elementary reactions chosen from all stoichiometrically possible reactions. The novelty of the approach lies in the fact that the user has to define all species involved (reactants, intermediates, products), and the rules applied with user-set limits reduce the resulting mechanism to a reasonable set of possible elementary reactions. The computer code consists of five parts: (i) definition of species, and introducing its characteristics (structure and thermodynamic data); (ii) definition of the reacting system and generation of all stoichiometrically possible reactions; (iii) reduction of the mechanisms using complexity and thermodynamic constraints based on user-set limits; (iv) calculation of the resulting pathways (routes of the various atoms or groups of atoms transferred from one species to another); and (v) tools to help visualization of the process by finding those elementary processes which realize a given pathway. Reasonable flexibility is ensured for using selection rules based on various criteria with limits set by the user. The various pathways are shown (in a matrix form), which offers an overview of the entire process.     

Ab initio molecular dynamics study of prebiotic production processes of organic compounds at meteorite impacts on ocean

Recent experiments concerning prebiotic materials syntheses suggest that the iron-bearing meteorite impacts on ocean during Late Heavy Bombardment provided abundant organic compounds associated with biomolecules such as amino acids and nucleobases. However, the molecular mechanism of a series of chemical reactions to produce such compounds is not well understood. In this study, we simulate the shock compression state of a meteorite impact for a model system composed of CO₂, H₂O, and metallic iron slab by ab initio molecular dynamics combined with multiscale shock technique, and clarify possible elementary reaction processes up to production of organic compounds. The reactions included not only pathways similar to the Fischer–Tropsch process known as an important hydrocarbon synthesis in many planetary processes but also those resulting in production of a carboxylic acid. It is also found that bicarbonate ions formed from CO₂ and H₂O participated in some forms in most of these observed elementary reaction processes. These findings would deepen the understanding of the full range of chemical reactions that could occur in the meteorite impact events. © 2018 Wiley Periodicals, Inc.     

Azulene-to-naphthalene rearrangement: the Car-Parrinello metadynamics method explores various reaction mechanisms.

We studied the thermal intramolecular and radical rearrangement of azulene to naphthalene by employing a novel metadynamics method based on Car-Parrinello molecular dynamics. We demonstrate that relatively short simulations can provide us with several possible reaction mechanisms for the rearrangement. We show that different choices of the collective coordinates can steer the reaction along different pathways, thus offering the possibility of choosing the most probable mechanism. We consider herein three intramolecular mechanisms and two radical pathways. We found the norcaradiene pathway to be the preferable intramolecular mechanism, whereas the spiran mechanism is the favored radical route. We obtained high activation energies for all the intramolecular pathways (81.5-98.6 kcal mol(-1)), whereas the radical routes have activation energies of 24-39 kcal mol(-1). The calculations have also resulted in elementary steps and intermediates not yet considered. A few attractive features of the metadynamics method in studying chemical reactions are pointed out.     

Comprehensive description of the photodegradation of bromophenols using chromatographic monitoring and chemometric tools

A general procedure for the study of complex photodegradation processes of environmental pollutants based on chromatographic monitoring and chemometric method is proposed. The procedure consists of multiset data analysis of aliquots collected at different reaction times and injected in High-Performance Liquid Chromatography coupled to diode array detection and mass spectrometry (HPLC-DAD-MS). In this study, photodegradation of six bromophenols with different degrees of bromination has been investigated in order to find out their photodegradation pathways and kinetics and to show the potential of the procedure proposed. Multivariate curve resolution-alternating least squares (MCR-ALS) has been used to resolve chromatographic elution profiles and pure spectra of species involved in the photodegradation process and, hence, to elucidate the photodegradation mechanism and to propose the chemical structure of the main photoproducts. This study shows that chromatographic monitoring is the preferred option when photochemical systems with large number of components with similar spectra and kinetic evolution are analyzed. This work reveals the advantages of the double DAD and MS detection to provide mechanistic and structural information about these complex photodegradation processes.     

A chemically consistent graph architecture for massive reaction networks applied to solid-electrolyte interphase formation

Modeling reactivity with chemical reaction networks could yield fundamental mechanistic understanding that would expedite the development of processes and technologies for energy storage, medicine, catalysis, and more. Thus far, reaction networks have been limited in size by chemically inconsistent graph representations of multi-reactant reactions (e.g. A + B → C) that cannot enforce stoichiometric constraints, precluding the use of optimized shortest-path algorithms. Here, we report a chemically consistent graph architecture that overcomes these limitations using a novel multi-reactant representation and iterative cost-solving procedure. Our approach enables the identification of all low-cost pathways to desired products in massive reaction networks containing reactions of any stoichiometry, allowing for the investigation of vastly more complex systems than previously possible. Leveraging our architecture, we construct the first ever electrochemical reaction network from first-principles thermodynamic calculations to describe the formation of the Li-ion solid electrolyte interphase (SEI), which is critical for passivation of the negative electrode. Using this network comprised of nearly 6000 species and 4.5 million reactions, we interrogate the formation of a key SEI component, lithium ethylene dicarbonate. We automatically identify previously proposed mechanisms as well as multiple novel pathways containing counter-intuitive reactions that have not, to our knowledge, been reported in the literature. We envision that our framework and data-driven methodology will facilitate efforts to engineer the composition-related properties of the SEI – or of any complex chemical process – through selective control of reactivity.

A chemically consistent graph architecture enables autonomous identification of novel solid-electrolyte interphase formation pathways from a massive reaction network.     

An automated method for graph-based chemical space exploration and transition state finding

Algorithms that automatically explore the chemical space have been limited to chemical systems with a low number of atoms due to expensive involved quantum calculations and the large amount of possible reaction pathways. The method described here presents a novel solution to the problem of chemical exploration by generating reaction networks with heuristics based on chemical theory. First, a second version of the reaction network is determined through molecular graph transformations acting upon functional groups of the reacting. Only transformations that break two chemical bonds and form two new ones are considered, leading to a significant performance enhancement compared to previously presented algorithm. Second, energy barriers for this reaction network are estimated through quantum chemical calculations by a growing string method, which can also identify non-octet species missed during the previous step and further define the reaction network. The proposed algorithm has been successfully applied to five different chemical reactions, in all cases identifying the most important reaction pathways.     

Decomposition of reaction networks: the initial phase of the permanganate/oxalic acid reaction

The determination of all chemical reaction networks composed of elementary reactions for a given net chemical reaction is one of the fundamental problems in chemistry, since the decomposition elucidates the reaction mechanism. It is essential in a wide range of applications: from the derivation of rate laws in physical chemistry to the design of large-scale reactors in process engineering where presence of unexpected side products can disturb operation. As an example we consider the well-known permanganate/oxalic acid reaction. We characterize all intermediate substances that can in principle act (auto-)catalytic, list all possible additional intermediate substances that would suffice to start the reaction without assuming presence of any autocatalyst. In particular, we propose for the first time a minimal network in which the well-known autocatalyst Mn²⁺ is produced. To derive our results we present an automatic method to determine whether a net chemical reaction can be explained by some reaction network with a given list of intermediate substances, how to generate all such networks, and how to suggest more intermediate substances if no network with the initially given substances exists.     

The Study of Alcoholysis of 1,2-Thiazetidine-l,l-dioxide with Quantum Chemical Method

The alcoholysis mechanism of 1,2-thiazetidine-1,1-dioxide with methanol, in which the relatively stable product is sulfonate ester, has been investigated by quantum chemical method. Our calculations indicate the reaction for alcoholysis of 1,2-thiazetidine-1,1-dioxide proceeds via two possible mechanisms: concerted and stepwise. In the stepwise mechanism, two possible reaction pathways can be followed while only one possible reaction pathway can be followed in the concerted mechanism.     

Skeletal and reduced chemical mechanism for hydrogen fluoride chemical laser

The chemical kinetics of supersonic hydrogen fluoride (HF) chemical lasers determines combustion characteristics and output power. However, the inherent complexity of chemical reactions and complex structure still challenge the numerical simulations involving a comprehensive chemical mechanism. Therefore, a high fidelity and low computational consuming model is important for design purpose. This paper presents a strategy to generate a reduced mechanism for HF chemical lasers. Based on a detailed HF chemical mechanism consisting of 16 species and 153 elementary reactions, a specific skeletal mechanism including 11 species and 58 elementary reactions is generated. Finally, we obtain a further reduction mechanism including 11 species and 39 elementary reactions by combining sensitivity analysis and rate of production analysis. The computational cost for simulation of supersonic HF chemical lasers with the reduced mechanism is less than that with the detailed model. The principal contribution of the work is to provide a low computational consuming model.     

State-to-state chemistry: An ab initio approach

It has become possible in recent years to compute state-to-state reaction crosssections and rate constants from first principles for a few elementary chemical reactions and for a few energy transfer processes. We illustrate the state-of-the art using examples of results obtained from our own laboratory.     

Proton mobility in water clusters

Proton mobility in water occurs quickly according to the so-called Grotthuss mechanism. This process and its elementary reaction steps can be studied in great detail by applying suitable mass spectrometric methods to ionic water clusters. Careful choice of suitable core ions in combination with analysis of cluster size trends in hydrogen/deuterium isotope exchange rates allows for detailed insights into fascinating dynamical systems. Analysis of the experiments has been promoted by extensive and systematic quantum chemical model calculations. Detailed low-energy mechanistic pathways for efficient water rearrangement and proton transfer steps, in particular cases along short preformed "wires" of hydrogen bonds, have been identified in consistency with experimental findings.     

Advances in the analysis of dynamic protein complexes by proteomics and data processing

Signal transduction governs virtually every cellular function of multicellular organisms, and its deregulation leads to a variety of diseases. This intricate network of molecular interactions is mediated by proteins that are assembled into complexes within individual signaling pathways, and their composition and function is often regulated by different post-translational modifications. Proteomic approaches are commonly used to analyze biological complexes and networks, but often lack the specificity to address the dynamic and hence transient nature of the interactions and the influence of the multiple post-translational modifications that govern these processes. Here we review recent developments in proteomic research to address these limitations, and discuss several technologies that have been developed for this purpose. The synergy between these proteomic and computational tools, when applied together with global methods to the analysis of individual proteins, complexes and pathways, may allow researchers to unravel the underlying mechanisms of signaling networks in greater detail than previously possible.     

Extracting the mechanisms and kinetic models of complex reactions from atomistic simulation data

Determining reaction mechanisms and kinetic models, which can be used for chemical reaction engineering and design, from atomistic simulation is highly challenging. In this study, we develop a novel methodology to solve this problem. Our approach has three components: (1) a procedure for precisely identifying chemical species and elementary reactions and statistically calculating the reaction rate constants; (2) a reduction method to simplify the complex reaction network into a skeletal network which can be used directly for kinetic modeling; and (3) a deterministic method for validating the derived full and skeletal kinetic models. The methodology is demonstrated by analyzing simulation data of hydrogen combustion. The full reaction network comprises 69 species and 256 reactions, which is reduced into a skeletal network of 9 species and 30 reactions. The kinetic models of both the full and skeletal networks represent the simulation data well. In addition, the essential elementary reactions and their rate constants agree favorably with those obtained experimentally. © 2019 Wiley Periodicals, Inc.     

Elementary processes in the radiation-induced degradation of poly(ethylene terephthalate)—A note

Elementary processes of γ-irradiated poly(ethylene terephthalate) (PET) have been investigated by electron spin resonance (esr) and optical absorption measurements. On irradiating PET films with γ-rays at ?196°C and in the dark, they develop a reddish purple color and show esr spectra which are assigned to ionic species of PET. The optical absorption spectra of γ-irradiated PET films at ?196°C and those of a model compound (diethylterephthalate(DET))-2-methyltetrahydrofuran system also confirm these assignments. A possible mechanism for the elementary processes of γ-ray-induced degradation of PET is proposed.     

Kinetics and mechanism of the catalytic reaction between alcohols and dimethyl carbonate

The mechanism of the reaction between alcohols and dimethyl carbonate, catalyzed by dicobalt octacarbonyl Co₂(CO)₈, is studied by means of mathematical modeling. Kinetic models for possible schemes of chemical transformations are constructed at different initial concentrations of the catalyst. Based on a comparative analysis of activation energies of possible stages of chemical transformations, possible reaction pathways are determined and an appropriate mechanism is selected.     

Aerobic oxidation of methanol to formic acid on Au20-: a theoretical study on the reaction mechanism

The aerobic oxidation of methanol to formic acid catalyzed by Au(20)(-) has been investigated quantum chemically using density functional theory with the M06 functional. Possible reaction pathways are examined taking account of full structure relaxation of the Au(20)(-) cluster. The proposed reaction mechanism consists of three elementary steps: (1) formation of formaldehyde from methoxy species activated by a superoxo-like anion on the gold cluster; (2) nucleophilic addition by the hydroxyl group of a hydroperoxyl-like complex to formaldehyde resulting in a hemiacetal intermediate; and (3) formation of formic acid by hydrogen transfer from the hemiacetal intermediate to atomic oxygen attached to the gold cluster. A comparison of the computed energetics of various elementary steps indicates that C-H bond dissociation of the methoxy species leading to formation of formaldehyde is the rate-determining step. A possible reaction pathway involving single-step hydrogen abstraction, a concerted mechanism, is also discussed. The stabilities of reactants, intermediates and transition state structures are governed by the coordination number of the gold atoms, charge distribution, cooperative effect and structural distortion, which are the key parameters for understanding the relationship between the structure of the gold cluster and catalytic activity in the aerobic oxidation of alcohols.