Synthesis of startable reaction pathways

2002

Stoichiometrically, exact candidate pathways or mechanisms for deriving the rate law of a catalytic or complex reaction can be determined through the synthesis of networks of plausible elementary reactions constituting such pathways. A rigorous algorithmic method is proposed for executing this synthesis, which is exceedingly convoluted due to its combinatorial complexity. Such a method for synthesizing networks of reaction pathways follows the general framework of a highly exacting combinatorial method established by us for process-network synthesis. It is based on the unique graph-representation in terms of P-graphs, a set of axioms, and a group of combinatorial algorithms. In the method, the inclusion or exclusion of a step of each elementary reaction in the mechanism of concern hinges on the general combinatorial properties of feasible reaction networks. The decisions are facilitated by solving linear programming problems comprising a set of mass-balance constraints to determine the existence or absence of any feasible solution. The search is accelerated further by exploiting the inferences of preceding decisions, thereby eliminating redundancy. As a result, all feasible independent reaction networks, i.e. pathways, are generated only once; the pathways violating any first principle of either stoichiometry or thermodynamics are eliminated. The method is also capable of generating those combinations of independent pathways directly, which are not microscopically reversible. The efficiency and efficacy of the method are demonstrated with the identification of the feasible mechanisms of ammonia synthesis involving as many as 14 known elementary reactions. : S 0 0 9 7 -8 4 8 5 ( 0 1 ) 0 0 1 1 9 -X

The Journal of Physical Chemistry B, 2005

The concept of reaction route (RR) graphs introduced recently by us for kinetic mechanisms that produce minimal graphs is extended to the problem of non-minimal kinetic mechanisms for the case of a single overall reaction (OR). A RR graph is said to be minimal if all of the stoichiometric numbers in all direct RRs of the mechanism are equal to (1 and non-minimal if at least one stoichiometric number in a direct RR is nonunity, e.g., equal to (2. For a given mechanism, four unique topological characteristics of RR graphs are defined and enumerated, namely, direct full routes (FRs), empty routes (ERs), intermediate nodes , and terminal nodes (TNs). These are further utilized to construct the RR graphs. One algorithm involves viewing each IN as a central node in a RR sub-graph. As a result, the construction and enumeration of RR graphs are reduced to the problem of balancing the peripheral nodes in the RR sub-graphs according to the list of FRs, ERs, INs, and TNs. An alternate method involves using an independent set of RRs to draw the RR graph while satisfying the INs and TNs. Three examples are presented to illustrate the application of non-minimal RR graph theory.

In this paper we discuss some general graph-theoretic formalism analogous to the chemical concepts of reactions and kits of reaction rules. We believe that this mathematical formalism may lead to improvements in Computer-assisted Organic Synthesis. Further we indicate that hypergraphs and its structure can be used to model the chemical reaction network.

The Journal of Chemical Physics, 1997

Mapping out a reaction mechanism involves optimizing the reactants and products, finding the transition state and following the reaction path connecting them. Transition states can be difficult to locate and reaction paths can be expensive to follow. We describe an efficient algorithm for determining the transition state, minima and reaction path in a single procedure. Starting with an approximate path represented by N points, the path is iteratively relaxed until one of the N points reached the transition state, the end points optimize to minima and the remaining points converged to a second order approximation of the steepest descent path. The method appears to be more reliable than conventional transition state optimization algorithms, and requires only energies and gradients, but not second derivative calculations. The procedure is illustrated by application to a number of model reactions. In most cases, the reaction mechanism can be described well using 5 to 7 points to represent the transition state, the minima and the path. The computational cost of relaxing the path is less than or comparable to the cost of standard techniques for finding the transition state and the minima, determining the transition vector and following the reaction path on both sides of the transition state.

Metabolic engineering, 2018

This paper describes how Rule Input Network Generator (RING), a network generation computational tool, can be adopted to generate a variety of complex biochemical reaction networks. The reaction language incorporated in RING allows representation of chemical compounds in biological systems with various structural complexity. Complex molecules such as oligosaccharides in glycosylation pathways can be described using a simplified representation of their monosaccharide building blocks and glycosidic bonds. The automated generation and topological network analysis features in RING also allow for: (1) constructing biochemical reaction networks in a rule-based manner, (2) generating graphical representations of the networks, (3) querying molecules containing a particular structural pattern, (4) finding the shortest synthetic pathways to a user-specified species, and (5) performing enzyme knockout to study their effect on the reaction network. Case studies involving three biochemical react...

Journal of Computational Chemistry, 1982

A complexity measure is proposed for the kinetic models of chemical reactions with linear mechanisms. The index is related to the structure of fractional-rational kinetic laws for chemical reactions, as well as to the structure of cyclic graphs used to describe them. The complexity index is shown to be closely related to the detailed hierarchical classification and to the code of linear reaction mechanisms, recently introduced. A number of index properties are proved for two-and threereaction routes. They reflect the influence of the various classification criteria, such as the number of reaction routes and intermediates, the type, class and subclasses of the mechanism, and the number of intermediates in each reaction route. Hierarchical levels of mechanisms with the same complexity (isocomplex mechanisms) are specified. Standard tables are presented with complexity indices for all topologically distinct linear reaction mechanisms having one to three reaction routes, two to six intermediates, and reversible elementary steps.

The Journal of Physical Chemistry A, 2017

We proposed and implemented a combined molecular dynamics and coordinate driving (MD/CD) method for automatically searching multistep reaction pathways of chemical reactions. In this approach, the molecular dynamic (MD) method at the molecular mechanics (MM) or semiempirical quantum mechanical (QM) level is employed to explore the conformational space of the minimum structures, and the modified coordinate driving (CD) method is used to build reaction pathways for representative conformers. The MD/CD method is first applied to two model reactions (the Claisen rearrangement and the intermolecular aldol reaction). By comparing the obtained results with those of the existing methods, we found that the MD/CD method has a comparable performance in searching low-energy reaction pathways. Then, the MD/CD method is further applied to investigate two reactions: the electrocyclic reaction of benzocyclobutene-7-carboxaldehyde and the intramolecular Diels−Alder reaction of ketothioester with 11 effectively rotatable single bonds. For the first reaction, our results can correctly account for its torquoselectivity. For the second one, our method predicts eight reaction channels, leading to eight different stereo-and regioselective products. The MD/CD method is expected to become an efficient and cost-effective theoretical tool for automatically searching low-energy reaction pathways for relatively complex chemical reactions.

The Journal of Chemical Physics, 2014

The Minima Hopping global optimization method uses physically realizable molecular dynamics moves in combination with an energy feedback that guarantees the escape from any potential energy funnel. For the purpose of finding reactions pathways, we argue that Minima Hopping is particularly suitable as a guide through the potential energy landscape and as a generator for pairs of minima that can be used as input structures for methods capable of finding transition states between two minima. For Lennard-Jones benchmark systems we compared this Minima Hopping guided path search method to a known approach for the exploration of potential energy landscapes that is based on deterministic mode-following. Although we used a stabilized mode-following technique that reliably allows to follow distinct directions when escaping from a local minimum, we observed that Minima Hopping guided path search is far superior in finding lowest-barrier reaction pathways. We therefore suggest that Minima Hopping guided path search can be used as a simple and efficient way to identify energetically low-lying chemical reaction pathways. Finally we applied the Minima Hopping guided path search approach to 75-atom and 102-atom Lennard Jones systems. For the 75-atom system we found pathways whose highest energies are significantly lower than the highest energy along the previously published lowest-barrier pathway. Furthermore, many of these pathways contain a smaller number of intermediate transition states than the previously publish lowest-barrier pathway. In case of the 102-atom system Minima Hopping guided path search found a previously unknown and energetically low-lying funnel. arXiv:1401.8081v2 [cond-mat.mtrl-sci]

AIChE Journal, 2019

West (Boston) Reforming Goldsmith and West, 2017 2.1 Chemical processes. One of the first examples of automated kinetic network generators is GRACE (Yoneda, 1979a), which was applied to build elementary reaction mechanisms for simple heterogenous catalytic processes. ReNGeP (Clymans and Froment, 1984) was originally proposed for the automated generation of reaction networks in the thermal cracking of normal and branched paraffins. The software starts with the characterization of the reactants and the reaction families that are stored in a database in the form of matrix operations. The relevant reaction families are applied to the reactants in a sequential manner. The generated products are also regarded as potential reactants to account for the reversibility of certain elementary steps. While the original version of the code was primarily applied to radical chemistry, it was later adapted to acidcatalyzed conversion of hydrocarbons. Recently, the code was extended to metal-catalyzed processes such as hydrogenation and Fischer-Tropsch synthesis. Another network generator that has been widely applied for microkinetic analysis of heterogeneous catalysis is MECHEM (Valdés-Pérez, 1992). The philosophy of this software involves generating the simplest reaction mechanisms, containing the fewest number of conjectured species and steps for a given a list of starting materials, observed products and userdefined constraints. NetGen (Broadbelt et al., 1994) is a versatile network generator that has been efficiently applied to model pyrolysis, heterogeneously-catalyzed processes, free-radical chemistry, and silicon nanoparticle growth. OxiGen (Iyer et al.

Journal of Chemical Information and Modeling, 1994

MECHEM is a computer aid for the elucidation of reaction pathways or mechanisms that has reached a promising level of competence at its task finding the simplest reaction pathways consistent with given experimental evidence and background chemical theory. The program has been applied to complex multistep reactions of hydrocarbon catalysis, with interesting results. However, the program could not reach its current level without several new heuristics. This article describes the heuristics, of which the most important is a divide-and-conquer strategy. Although our focus is on systematic methods, it is noteworthy that standard references on reaction mechanism elucidation do not mention these heuristics.