Imaginary Transition Research Articles

Partial Imaginary Transition State (ITS) Graphs: A Formal Framework for Research and Analysis of Atom-to-Atom Maps of Unbalanced Chemical Reactions and Their Completions

Atom-to-atom maps (AAMs) are bijections that establish the correspondence of reactant and product atoms across chemical reactions. They capture crucial features of the reaction mechanism and thus play a central role in modeling chemistry at the level of graph transformations. AAMs are equivalent to so-called “imaginary transition state” (ITS) graphs, making it possible to reduce tasks such as the computational comparison of AAMs to testing graph isomorphisms. In many application scenarios, nonetheless, only partial information is available, i.e., only partial maps or, equivalently, only subgraphs of the ITS graphs, are known. Here, we investigate whether and how, and to what extent, such partial chemical data can be completed and compared. The focus of this contribution is entirely on the development of a solid mathematical foundation for the analysis of partial AAMs and their associated partial ITS graphs.

Comparison of Atom Maps

The computation of reliable, chemically correct atom maps from educt/product pairs has turned out to be a difficult problem in cheminformatics because the chemically correct solution is not necessarily an optimal solution for combinatorial formulations such as maximum common subgraph problems. As a consequence, competing models have been devised and compared in extensive benchmarking studies. Due to isomorphisms among products and educts it is not immediately obvious, however, when two atom maps for a given educt/product pairs are the same. We formalize here the equivalence of atom maps and show that equivalence of atom maps is in turn equivalent to the isomorphism of labeled auxiliary graphs. In particular, we demonstrate that Fujita's Imaginary Transition State can be used for this purpose. Numerical experiments show that practical feasibility. Generalizations to the equivalence of subgraph matches, double pushout graph transformation rules, and mechanisms of multi-step reactions are discussed briefly.

Representing Catalytic Mechanisms with Rule Composition.

An "imaginary transition structure" overlays the molecular graphs of the educt and product sides of an elementary chemical reaction in a single graph to highlight the changes in bond structure. We generalize this idea to reactions with complex mechanisms in a formally rigorous approach based on composing arrow-pushing steps represented as graph-transformation rules to construct an overall composite rule and a derived transition structure. This transition structure retains information about transient bond changes that are invisible at the overall level and can be constructed automatically from an existing database of detailed enzymatic mechanisms. We use the construction to (i) illuminate the distribution of catalytic action across enzymes and substrates and (ii) to search in a large database for reactions of known or unknown mechanisms that are compatible with the mechanism captured by the constructed composite rule.

EHreact: Extended Hasse Diagrams for the Extraction and Scoring of Enzymatic Reaction Templates.

Data-driven computer-aided synthesis planning utilizing organic or biocatalyzed reactions from large databases has gained increasing interest in the last decade, sparking the development of numerous tools to extract, apply, and score general reaction templates. The generation of reaction rules for enzymatic reactions is especially challenging since substrate promiscuity varies between enzymes, causing the optimal levels of rule specificity and optimal number of included atoms to differ between enzymes. This complicates an automated extraction from databases and has promoted the creation of manually curated reaction rule sets. Here, we present EHreact, a purely data-driven open-source software tool, to extract and score reaction rules from sets of reactions known to be catalyzed by an enzyme at appropriate levels of specificity without expert knowledge. EHreact extracts and groups reaction rules into tree-like structures, Hasse diagrams, based on common substructures in the imaginary transition structures. Each diagram can be utilized to output a single or a set of reaction rules, as well as calculate the probability of a new substrate to be processed by the given enzyme by inferring information about the reactive site of the enzyme from the known reactions and their grouping in the template tree. EHreact heuristically predicts the activity of a given enzyme on a new substrate, outperforming current approaches in accuracy and functionality.

Learning to Reweight Imaginary Transitions for Model-Based Reinforcement Learning

Model-based reinforcement learning (RL) is more sample efficient than model-free RL by using imaginary trajectories generated by the learned dynamics model. When the model is inaccurate or biased, imaginary trajectories may be deleterious for training the action-value and policy functions. To alleviate such problem, this paper proposes to adaptively reweight the imaginary transitions, so as to reduce the negative effects of poorly generated trajectories. More specifically, we evaluate the effect of an imaginary transition by calculating the change of the loss computed on the real samples when we use the transition to train the action-value and policy functions. Based on this evaluation criterion, we construct the idea of reweighting each imaginary transition by a well-designed meta-gradient algorithm. Extensive experimental results demonstrate that our method outperforms state-of-the-art model-based and model-free RL algorithms on multiple tasks. Visualization of our changing weights further validates the necessity of utilizing reweight scheme.

2.2]Paracyclophane-Based Chiral Platforms for Circularly Polarized Luminescence Fluorophores and Their Chiroptical Properties: Past and Future.

Quality of CPL fluorophore is defined by the vectors of electric dipole transition moment and imaginary magnetic dipole transition moment. The aim of this review is to introduce readers to a chiral moiety applicable to CPL studies focusing on chiral cyclophanes because the rigid cyclophanes are able to hold the vector directions of electric dipole transition moment and imaginary magnetic dipole transition moment.

Capital in Transition

Abstract Migrant children are an unintended consequence of the widened rural-urban gap in China. In Dengfeng, a county-level city in central China, many of the 70,000 full-time martial arts students were rural-to-urban migrant children ‘floating’ with their parents from one place to another. Drawing on 12 months of ethnographic fieldwork, this paper explores why these migrant children ‘migrated’ to martial arts schools for educational purposes and how they and their parents seek to establish a new value system within which different forms of capital can be accumulated, disseminated, and transformed as society expects. This paper argues that the (imaginary) transition between and flow of economic, cultural, social, and symbolic capital construct a path to an aspirational future used by both these martial arts students and their parents.

Half-Century Journey from Synthetic Organic Chemistry to Mathematical Stereochemistry through Chemoinformatics

My half-century journey started from synthetic organic chemistry. During the first stage of my journey, my interest in stereochemistry was initiated through the investigation on the participation of steric effects in reactive intermediates, cylophanes, strained heterocycles, and organic compounds for photography. In chemoinformatics as the next stage of the journey, I proposed the concept of imaginary transition structures (ITSs) as computer-oriented representation of organic reactions. My interest was stimulated to attack combinatorial enumeration through the investigation on enumeration of subgraphs of ITSs. Stereochemistry and combinatorial enumeration was combined in my interest, so that I reached mathematical stereochemistry as the final stage of my journey. Fujita's unit-subduced-cycle-index (USCI) approach, Fujita's proligand method, and Fujita's stereoisogram approach were developed, so as to integrate van't Hoff's way (asymmetry, stereogenicity) and Le Bel's way (dissymmetry, chirality), which caused continuous confusion in the history of stereochemistry.

Imaginary Transitions and Transformation in Psychoanalytic Work.

This article explores the transformations that occur in analytic work from methodological, topographical, and dynamic perspectives, with a particular emphasis on the concept of imaginary transition. Through a theoretical exploration and the presentation of clinical material from five cases, the authors show how the process of working-through emerges in treatment as a result of the changes of rhythm, register, images, phenomena of upheaval, and the numerous displacements that are brought about in and through transference. Events are only markers or clues about a transformation that takes place over the long term.

Atom mapping with constraint programming

Chemical reactions are rearrangements of chemical bonds. Each atom in an educt molecule thus appears again in a specific position of one of the reaction products. This bijection between educt and product atoms is not reported by chemical reaction databases, however, so that the “Atom Mapping Problem” of finding this bijection is left as an important computational task for many practical applications in computational chemistry and systems biology. Elementary chemical reactions feature a cyclic imaginary transition state (ITS) that imposes additional restrictions on the bijection between educt and product atoms that are not taken into account by previous approaches. We demonstrate that Constraint Programming is well-suited to solving the Atom Mapping Problem in this setting. The performance of our approach is evaluated for a manually curated subset of chemical reactions from the KEGG database featuring various ITS cycle layouts and reaction mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13015-014-0023-3) contains supplementary material, which is available to authorized users.

ChemInform Abstract: Automatic Determination of Reaction Mappings and Reaction Center Information. Part 1. The Imaginary Transition State Energy Approach.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Automatic Determination of Reaction Mappings and Reaction Center Information. 2. Validation on a Biochemical Reaction Database

The correct identification of the reacting bonds and atoms is a prerequisite for the analysis of the reaction mechanism. We have recently developed a method based on the Imaginary Transition State Energy Minimization approach for automatically determining the reaction center information and the atom-atom mapping numbers. We test here the accuracy of this ITSE approach by comparing the predictions of the method against more than 1500 manually annotated reactions from BioPath, a comprehensive database of biochemical reactions. The results show high agreement between manually annotated mappings and computational predictions (98.4%), with significant discrepancies in only 24 cases out of 1542 (1.6%). This result validates both the computational prediction and the database, at the same time, as the results of the former agree with expert knowledge and the latter appears largely self-consistent, and consistent with a simple principle. In 10 of the discrepant cases, simple chemical arguments or independent literature studies support the predicted reaction center. In five reaction instances the differences in the automatically and manually annotated mappings are described in detail. Finally, in approximately 200 cases the algorithm finds alternate reaction centers, which need to be studied on a case by case basis, as the exact choice of the alternative may depend on the enzyme catalyzing the reaction.

Automatic Determination of Reaction Mappings and Reaction Center Information. 1. The Imaginary Transition State Energy Approach

Chemical reactions transform the reactant molecules by deleting existing and forming new bonds. The identification of these so-called reacting bonds is important for studying the reaction mechanism and for applications in metabolomics, e.g. for interpreting substrate labeling experiments. Here, we introduce an approach which suggests the simplest possible reaction center at the heavy atom level, with high accuracy. In contrast to current methods the approach is motivated by a simple theoretical model based on a crude approximation of the reaction energetics, and takes the complete reacting system into account. Finally, it recovers all optimal solutions to the problem while removing all symmetry-related, redundant solutions. We apply the method on the complete KEGG database of biochemical reactions, and compare our approach with previous methods. The resulting reaction centers are represented as imaginary transition states, which are molecule-like representations of reaction mechanisms. We provide the statistics of the calculations on the KEGG database and discuss some examples for the different types of alternative solutions found.

ChemDrawの反応データの虚遷移構造(ITS)データ形式への変換

ChemDrawの反応データの虚遷移構造(ITS)データ形式への変換

Why are smaller fragments preferentially lost from radical cations at low energies and larger ones at high energies?: An experimental and theoretical study

A long-standing mystery in gas phase ion chemistry is: why are smaller fragments preferentially lost at low energies and larger fragments at higher energies in competing α-cleavages? This is addressed here by studies of dissociations of ethanol, 2-propanol, 2-butanol, 2-methylpropane and 2-butanone radical cations. The onsets and energy dependencies of the reactions were obtained by photoionization mass spectrometry. Stationary point geometries, critical energies and vibrational frequencies were generated by B3LYP/6-31G(d) and B3LYP/6-311G(d,p) theory (DFT). Dependencies of reaction rates on internal energy were calculated by Rice–Ramsperger–Kassel–Marcus (RRKM) theory. Results obtained establish the generality of a previous finding that loss of H is slower than competing losses of polyatomic fragments. This is attributable to substantial lowering of the frequencies of the vibrations that are converted to rotations and translations in the transition states for the latter reactions, but not in transition states for H losses. It is concluded that lower dissociation thresholds produce preferred losses of smaller alkyl fragments at low energies and that looser transition states favor losses of larger fragments at higher energies. DFT results and abundances of parallel alkane eliminations (two step processes also initiated by simple CC bond cleavage) indicate that cleavage of the CC bond to the larger alkyl fragment is most frequent even below the threshold for complete dissociation (energies at which ion-induced dipole alkyl complexes are formed), i.e., at all energies of bond cleavage, even if not reflected in simple cleavage abundances near threshold. Obtaining realistic rates by RRKM theory required increasing the lowest transition state vibrational frequencies (for modes that become rotations and translations) to well above those obtained by DFT for alkyl losses, further evidence that the rates of those reactions are controlled by minimum entropy transition states occurring earlier than the single imaginary frequency transition states found by DFT. In addition, comparison of DFT critical energies, photoionization critical energies and critical energies that give the best RRKM rates support relaxation of the ground states to lower energy species with long CC bonds following ionization. Preferred losses of larger alkanes at low energies, dominant losses of larger alkyl groups at high energies and formation of long CC bonds to the larger alkyl in the ground state ion all appear to have a common origin.

ITSProducer．虚遷移構造 (ITS) をキーとする既存の有機反応データベース検索システムの実装

ITSProducer．虚遷移構造 (ITS) をキーとする既存の有機反応データベース検索システムの実装

ITSProducer --- A Search Engine for Organic-Reaction Database by Means of Imaginary Transition Structures

ITSProducer --- A Search Engine for Organic-Reaction Database by Means of Imaginary Transition Structures

Enumeration of organic reactions by counting substructures of imaginary transition structures. Importance of orbits governed by coset representations

Two methods for the enumeration of organic reactions are presented in order to take obligatory minimum valencies of a given skeleton into consideration. The first method is a generalization of Polya's theorem, in which the transitivity of the positions of the skeletons is explicitly considered. Thus, a permutation representation acting on the positions is reduced into cosec representations (CRs). In accord with this reduction, unit cycle indices derived from the CRs construct a generalized cycle index. The second method is based on the subduction of the coset representations. This contains useful concepts such as unit subduced cycle indices and subduced cycle index that afford a new type of generating functions.

Graphic characterization and taxonomy of organic reactions

This paper deals with the substructures of imaginary transition structures as one of the integrated systems for representing organic reactions.

ChemInform Abstract: Formulation of Isomeric Reaction Types and Systematic Enumeration of Six‐Electron Pericyclic Reactions.

AbstractA novel formulation of reaction types is described, based on the concept of imaginary transition structures.