Reaction Rules Research Articles

Computer‐aided synthesis design: 40 years on

AbstractThe discipline of retrosynthetic analysis is now just over 40 years old. From the earliest day, attempts were made to incorporate this approach into computer programs to test the extent in which chemical perception and synthetic thinking could be formalized. Despite pioneering research efforts, computer‐aided synthetic analysis failed to achieve widespread routine use by chemists, which can be attributed in part to the difficulty of building the required high‐quality retrosynthetic transform databases required for credible analyses. However, with the advent over the past 25 years of large comprehensive reaction databases, work on successfully automating the construction of reliable and comprehensive reaction rule databases is promising to revitalize research in this field. This review compares and contrasts the diverse approaches taken by selected programs in both the design and implementation of molecule feature perception and reaction rule representation, and we review the concepts of synthetic strategy selection, representation, and execution. In particular, we discuss the current work on automating the construction of reliable and comprehensive synthetic rule sets from available reaction databases in newer programs such as ARChem. We argue that the progress achieved in this aspect paves the way to a deeper exploration of computer approaches to applying strategy and control in the synthesis problem. © 2011 John Wiley & Sons, Ltd.This article is categorized under: Computer and Information Science > Chemoinformatics

Kinetics and Reaction Pathways of Formaldehyde Degradation Using the UV‐Fenton Method

This study was based on the purpose of investigating the reaction rules of formaldehyde (HCHO) as an intermediate product in the degradation of many other organic wastewaters. The process conditions of UV-Fenton method for the degradation of the low concentrations of HCHO were studied in a batch photochemical reactor. The results showed that, when the original HCHO concentration was 30 mg/L, at an operating temperature of 23 degrees C, pH = 3, an H202 dosage of 68 mg/L, and an H2O2-to-Fe2+ mole ratio (H2O2:Fe2+) of 5, 91.89% of the HCHO was removed after 30 minutes. The degradation of HCHO in the UV-Fenton system was basically in accordance with the exponential decay. The kinetic study results showed that the reaction orders of HCHO, Fe2+, and H2O2 in the system were 1.054, 0.510, and 0.728, respectively, and the activation energy (Ea) was 9.85 kJ/mol. The comparison of UV/H2O2, Fenton, and UV-Fenton systems for the degradation of HCHO, and the results of iron catalyst tests showed that the mechanism of UV-Fenton on the degradation of HCHO was through a synergistic effect of Fe2+ and UV light to catalyze the decomposition of H2O2. The introduction of UV irradiation to the Fenton system largely increased the degradation rate of HCHO, mainly as a result of the accelerating effect on the formation of the Fe2+/Fe3+ cycle. The reaction products were analyzed by gas chromatography-mass spectrometry and a chemical oxygen demand (COD) analyzer. The effluent gases also were analyzed by gas chromatography. Based on those results, the reaction pathways of HCHO in the UV-Fenton system were proposed. The qualitative and quantitative analysis of the reaction products and the COD showed that the main intermediate product of the reaction was formic acid, and the further oxidation of it was the rate-limiting step for the degradation of HCHO.

Van der Waals effect in weak adsorption affecting trends in adsorption, reactivity, and the view of substrate nobility

The ubiquitous van der Waals (vdW) force, particularly discernible in weak adsorption, is studied on noble and transition metals. In calculations with the vdW density functional (DF) [M. Dion et al., Phys. Rev. Lett. 92, 246401 (2004)], the atomic structure near the adsorption site is systematically varied, including dense fcc(111) surface, adatom, pyramid, and step defects. In weak adsorption the vdW force (i) is shown necessary to account for, (ii) is sizable, (iii) has a strong spatial variation, relevant for adsorption on surface defects, (iv) changes reaction rules, and (v) changes adsorption trends in agreement with experimental data. Traditional physisorption theory is also given support and interpretation.

Ab initio study on the mechanism of cycloaddition reaction between H2Si=Si: and formaldehyde

The mechanism of the cycloaddition reaction between singlet H2Si=Si: and formaldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has three competitive dominant reaction pathways. The reaction rules presented is that the 3p unoccupied orbital of the Si: atom in H2Si=Si: inserts the π orbital of formaldehyde from the oxygen side, resulting in the formation of an intermediate. Isomerization of the intermediate further generates a four-membered ring silylene (the H2Si–O in the opposite position). In addition, the [2+2] cycloaddition reaction of the two π-bonds in H2Si=Si: and formaldehyde also generates another four-membered ring silylene (the H2Si–O in the syn-position). Because of the unsaturated property of the Si: atom in the two four-membered ring silylenes, the two four-membered ring silylenes could further react with formaldehyde, generating two silicic bis-heterocyclic compounds. Simultaneously, the ring strain of the four-membered ring silylene (the H2Si–O in the syn-position) makes it isomerize to a twisted four-membered ring product.

Photosynthetic algorithm approaches for bioinformatics

Photosynthetic algorithm (PA) is the newly biosystem-derived heuristic search algorithm that utilizes the dark reaction rules governing the transfer of carbon molecules from one substance into another in the Calvin–Benson cycle and photorespiration. There are only two works using this new algorithm in the literature, one for finite element analysis and one for N-queen problem. This paper presents PA based novel solution techniques in bioinformatics problems such as aligning multiple sequences and discovering association rules within bio-medical data. The simulation results demonstrate the applicability and potential of this algorithm.

ON THE RELATION BETWEEN ORGANIZATIONS AND LIMIT SETS IN CHEMICAL REACTION SYSTEMS

Chemical organization theory has been suggested as a new approach to analyze complex reaction networks. Concerning the long-term behavior of the network dynamics we will study its foundations mathematically. Therefore we consider a chemical reactor containing molecules of different species reacting with each other according to a set of reaction rules. We further assume that the dynamical behavior of the concentration of each species is given by a continuous chemical ordinary differential equation. Abstracting from dedicated concentration values we consider a discrete problem: Which species can appear in the reactor after a long time? We define the limit set abstraction, which contains the subsets of species characterizing the long-term behavior. We prove that all these subsets are closed and that for all bounded limit sets, at least one of them is self-maintaining and thus is an organization. This implies for a chemical ordinary differential equation systems that any attractor that does not touch the state space boundaries (in particular, any periodic attractor) lies within one organization, that is, the set of species with positive concentrations in any state of such an attractor is an organization. This in turn explains why in a deterministic system evolving according to reaction rules one can observe species sets that are closed and self-maintaining, thus organizations.

Efficient modeling, simulation and coarse-graining of biological complexity with NFsim

Managing the overwhelming numbers of molecular states and interactions is a fundamental obstacle to building predictive models of biological systems. Here we introduce the Network-Free Stochastic Simulator (NFsim), a general-purpose modeling platform that overcomes the combinatorial nature of molecular interactions. Unlike standard simulators that represent molecular species as variables in equations, NFsim uses a biologically intuitive representation: objects with binding and modification sites acted on by reaction rules. During simulations, rules operate directly on molecular objects to produce exact stochastic results with performance that scales independently of the reaction network size. Reaction rates can be defined as arbitrary functions of molecular states to provide powerful coarse-graining capabilities, for example to merge Boolean and kinetic representations of biological networks. NFsim enables researchers to simulate many biological systems that were previously inaccessible to general-purpose software, as we illustrate with models of immune system signaling, microbial signaling, cytoskeletal assembly and oscillating gene expression.

Programming in Biomolecular Computation

Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We introduce a model of computation that is evidently programmable, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only executable, but are also compilable and interpretable. It is universal: all computable functions can be computed (in natural ways and without arcane encodings of data and algorithm); it is also uniform: new “hardware” is not needed to solve new problems; and (last but not least) it is Turing complete in a strong sense: a universal algorithm exists, that is able to execute any program, and is not asymptotically inefficient.A prototype model has been implemented (for now in silico on a conventional computer). This work opens new perspectives on just how computation may be specified at the biological level.

The Lumping Kinetic Model for the Heavy Oil Catalytic Cracking MIP Process

Based on the characteristics of heavy oil catalytic cracking and maximizing iso-paraffins (MIP) process, a 12-lumping kinetic model was developed in this article to simulate the MIP process. According to the published data from a commercial MIP process, 36 kinetic parameters of the model were determined by the stepwise method. The verification result with industrial data showed that the model could predict not only the distribution of products but also the quality of main products and describe the reaction rules of the MIP process correctly.

Innovative approach of low carbon and efficient utilization of coal resources: The polygeneration system of a combination of the gasified coal gas and the pyrolyzed coal gas to form the synthetic gas

The present status of fossil energy resources in China reveals the fact that coal is the main energy supplier and the increasing and massive exploitation of coal and its application process such as coal burning cause serious environmental pollution which is the common concern of the government and the people. The development of low-carbon technology and the clean and efficient utilization of coal which is the high carbon resource are crucial in China’s energy development, and that is one of the ultimate goals of the Chinese social development. To realize this goal, the State Key Development Program for the Basic Research of China (973 project) (Grant No. CB2005CB221200), a national basic research project of “Applied basic researches on polygeneration system of a combination of the gasified coal gas and the pyrolyzed coal gas to form the synthetic gas” taken charge of by Taiyuan University of Technology started in 2005 supported by the Ministry of Science and Technology, more than ten other universities and research institutes have also taken part in it. This is a polygeneration project based on China’s actual conditions and the main idea is to make syngas through reforming of partial gasified gas and coke oven gas. The main products of this project are alcohol ether fuel and power. The innovative idea of this project is the reforming of coke oven gas (rich in H2 and CH4) and the gasified gas (rich in CO and CO2) to obtain syngas with optimum composition, so that it can replace the traditional way of H2 production through CO conversion, thus both CO2 emission and water consumption are reduced. Sensible feedstock composition and rational and terraced utilization of products can be realized by the polygeneration of coke, alcohol ether fuel and power. The main research aspects of this project include the following. 1) The engineering rationale of large-scale fluidized-bed pressurized gasification of coal with dual gas feed for polygeneration. 2) The reaction rule of reforming the coke oven gas and gasified gas with the presence of pyrocarbon and hydrogen adjustment without shift conversion. 3) The basic researches of desulphurization purification system under the complicated polygeneration conditions. 4) Preparation of the slurry bed catalyst and the base of new liquid phase synthesis technology. 5) Rules of intensification and control of the slurry bed based synthesis of the alcohol ether fuel, heterogeneous catalysis reaction and the integrated reaction and separation. 6) Controlled combustion in the gas turbine of the purge gas and crude gas generated during polygeneration. 7) The systematic and integrated theory of polygeneration is based on the mechanism of comprehensive and terraced utilization of chemical energy and physical energy. The five years of study resulted in remarkable progress and significant achievement which are mentioned in the above seven aspects. The main study achievements of this project can be enumerated as the following.

Detailed chemical kinetic reaction mechanism for biodiesel components methyl stearate and methyl oleate

New chemical kinetic reaction mechanisms are developed for two of the five major components of biodiesel fuel, methyl stearate and methyl oleate. The mechanisms are produced using existing reaction classes and rules for reaction rates, with additional reaction classes to describe other reactions unique to methyl ester species. Mechanism capabilities were examined by computing fuel/air autoignition delay times and comparing the results with more conventional hydrocarbon fuels for which experimental results are available. Additional comparisons were carried out with measured results taken from jet-stirred reactor experiments for rapeseed oil methyl ester fuels. In both sets of computational tests, methyl oleate was found to be slightly less reactive than methyl stearate, and an explanation of this observation is made showing that the double bond in methyl oleate inhibits certain low temperature chain branching reaction pathways important in methyl stearate. The resulting detailed chemical kinetic reaction mechanism includes more approximately 3500 chemical species and more than 17,000 chemical reactions.

RuleMonkey: software for stochastic simulation of rule-based models

BackgroundThe system-level dynamics of many molecular interactions, particularly protein-protein interactions, can be conveniently represented using reaction rules, which can be specified using model-specification languages, such as the BioNetGen language (BNGL). A set of rules implicitly defines a (bio)chemical reaction network. The reaction network implied by a set of rules is often very large, and as a result, generation of the network implied by rules tends to be computationally expensive. Moreover, the cost of many commonly used methods for simulating network dynamics is a function of network size. Together these factors have limited application of the rule-based modeling approach. Recently, several methods for simulating rule-based models have been developed that avoid the expensive step of network generation. The cost of these "network-free" simulation methods is independent of the number of reactions implied by rules. Software implementing such methods is now needed for the simulation and analysis of rule-based models of biochemical systems.ResultsHere, we present a software tool called RuleMonkey, which implements a network-free method for simulation of rule-based models that is similar to Gillespie's method. The method is suitable for rule-based models that can be encoded in BNGL, including models with rules that have global application conditions, such as rules for intramolecular association reactions. In addition, the method is rejection free, unlike other network-free methods that introduce null events, i.e., steps in the simulation procedure that do not change the state of the reaction system being simulated. We verify that RuleMonkey produces correct simulation results, and we compare its performance against DYNSTOC, another BNGL-compliant tool for network-free simulation of rule-based models. We also compare RuleMonkey against problem-specific codes implementing network-free simulation methods.ConclusionsRuleMonkey enables the simulation of rule-based models for which the underlying reaction networks are large. It is typically faster than DYNSTOC for benchmark problems that we have examined. RuleMonkey is freely available as a stand-alone application http://public.tgen.org/rulemonkey. It is also available as a simulation engine within GetBonNie, a web-based environment for building, analyzing and sharing rule-based models.

Synthetic Mechanochemical Molecular Swimmer

A minimal design for a molecular swimmer is proposed that is based on a mechanochemical propulsion mechanism. Conformational changes are induced by electrostatic actuation when specific parts of the molecule temporarily acquire net charges through catalyzed chemical reactions involving ionic components. The mechanochemical cycle is designed such that the resulting conformational changes would be sufficient for achieving low Reynolds number propulsion. The system is analyzed within the recently developed framework of stochastic swimmers to take account of the noisy environment at the molecular scale. The swimming velocity of the device is found to depend on the concentration of the fuel molecule according to the Michaelis-Menten rule in enzymatic reactions.

Rule-based spatial modeling with diffusing, geometrically constrained molecules

BackgroundWe suggest a new type of modeling approach for the coarse grained, particle-based spatial simulation of combinatorially complex chemical reaction systems. In our approach molecules possess a location in the reactor as well as an orientation and geometry, while the reactions are carried out according to a list of implicitly specified reaction rules. Because the reaction rules can contain patterns for molecules, a combinatorially complex or even infinitely sized reaction network can be defined.For our implementation (based on LAMMPS), we have chosen an already existing formalism (BioNetGen) for the implicit specification of the reaction network. This compatibility allows to import existing models easily, i.e., only additional geometry data files have to be provided.ResultsOur simulations show that the obtained dynamics can be fundamentally different from those simulations that use classical reaction-diffusion approaches like Partial Differential Equations or Gillespie-type spatial stochastic simulation. We show, for example, that the combination of combinatorial complexity and geometric effects leads to the emergence of complex self-assemblies and transportation phenomena happening faster than diffusion (using a model of molecular walkers on microtubules). When the mentioned classical simulation approaches are applied, these aspects of modeled systems cannot be observed without very special treatment. Further more, we show that the geometric information can even change the organizational structure of the reaction system. That is, a set of chemical species that can in principle form a stationary state in a Differential Equation formalism, is potentially unstable when geometry is considered, and vice versa.ConclusionsWe conclude that our approach provides a new general framework filling a gap in between approaches with no or rigid spatial representation like Partial Differential Equations and specialized coarse-grained spatial simulation systems like those for DNA or virus capsid self-assembly.

An extensible, maintainable and elegant approach to hardware source code generation in Reconfig-P

Reconfig-P is a prototype hardware implementation for membrane computing applications. Currently there are two alternative designs for the implementation of P systems in Reconfig-P: the rule-oriented design and the region-oriented design. Driven by the goal of high performance, the rule-oriented design treats reaction rules as the primary computational entities and represents regions only implicitly. In contrast, the region-oriented design represents regions, rather than reaction rules, as the primary computational entities, and thereby more directly reflects the intuitive conceptual understanding of a P system and promotes the extensibility of Reconfig-P. To improve its practical usefulness and versatility, not only should Reconfig-P include both of the hardware designs, it should be maintainable and extensible so that it can easily and effectively incorporate new implementation strategies and implementations of additional types of P systems. To accomplish a seamless integration of the rule-oriented and region-oriented designs and other alternative implementation strategies in Reconfig-P, and to make Reconfig-P amenable to future integration of additional implementation strategies, we have developed a new version of P Builder, our intelligent hardware source code generator, in accordance with a novel design pattern called Content-Form-Strategy. In this paper, we describe the Content-Form-Strategy pattern and the implementation of the new version of P Builder.

Diffusion and oxidation wear of PCBN tool based on thermodynamics

The rules of diffusion wear and oxidation wear for PCBN cutting tools were analyzed based on thermodynamics theory. Dissolution concentrations in typical normal workpice materials of PCBN tool material at different temperature were then calculated. Diffusion reaction rules in high temperature were developed and analyzed using the Gibbs free energy criterion. The machining tests were conducted using the PCBN tools at different cutting speeds of 50, 95,100 and 180 m/min, feed of 0.1, 0.2 and depth of cut of 0.1, 0.8, 1, and 1.5 mm respectively on a PUMA300LM numerically-controlled lathe. It was found that the theoretical results were uniform with the experimental data, and the results will provide useful references for tool material design and selection.

Detailed Kinetic Model for the Hydro-desulfurization of FCC Naphtha

A detailed kinetic model has been developed that describes the selective hydro-desulfurization chemistry of FCC naphtha at minimal olefin saturation. The FCC naphtha is represented by 348 molecular lumps measured by different gas-chromatographic methods. The reaction chemistry is specified in terms of reaction rules using the structure-oriented lumping (SOL) framework. A total of 15 reaction rules, which describe 444 individual reaction steps, have been used to model the governing chemistry. Relative reactivity relationships among different molecular lumps within the same rule have been derived using model feeds or established results from the literature. The kinetic parameters have been estimated from a comprehensive experimental data set comprising of both pilot plant and commercial refinery data spanning a wide range of process conditions and feed compositions. The kinetic model quantitatively predicts the product composition, product properties, extent of hydro-desulfurization, olefin saturation, and the associated octane loss. The modeling framework is generic to naphtha hydroprocessing technologies, and its specific application to the Selective CAtalytic Naphtha hydrofining (SCANfining) process, a proprietary technology of ExxonMobil, is demonstrated.

Thermodynamical matching of alumina-based composite ceramic tools with typical workpiece materials

Cutting temperature always highly reaches to over 1,000°C during high speed. Diffusion of tool material element may have important influence on tool wear at such high temperature. The advanced ceramic cutting tools have very good wear resistance, high refractoriness, good mechanical strength, and hot hardness. In this paper, the rules of diffusion wear for alumina-based ceramic cutting tools are proposed and analyzed based on thermodynamics theory. Dissolution concentrations in typical normal workpiece materials of ceramic tool materials at different temperatures are then calculated. Diffusion reaction rules in high temperature are developed and analyzed using Gibbs free energy criterion. The machining tests were conducted using the alumina-based composite ceramic tools at different cutting speeds of 10, 150, and 250 m/min, feed of 0.2 and 0.3, and depth of cut of 1, 2, 2.5, and 5 mm, respectively, on PUMA300LM numerically controlled lathe. It was found that the theoretical results were uniform with the experimental data; the results will provide useful references for tool material design and selection.

Organization-Oriented Chemical Programming of Distributed Artifacts

The construction of molecular-scale machines requires novel paradigms for their programming. Here, we assume a scenario of distributed devices that process in-formation by chemical reactions and that communicate by exchanging molecules. Programming such a distributed system requires specifing reaction rules as well as exchange rules. Here, we present an approach that helps to guide the manual construction of distributed chemical programs. We show how chemical organization theory can assist a programmer in predicting the behavior of the program. The basic idea is that a computation should be understood as a movement between chemical organizations, which are closed and self-maintaining sets of molecular species. When sticking to that design principle, fine-tuning of kinetic laws becomes less important. We demonstrate the approach by a novel chemical program that solves the maximal independent set problem on a distributed system without any central control—a typical situation in ad-hoc networks. We show that the computational result, which emerges from many local reaction events, can be explained in terms of chemical organizations, which assures robustness and low sensitivity to the choice of kinetic parameters.

Analysis of 120 cues of adverse drug reaction

Objective To analyze the characteristics and rules of adverse drug reaction(ADR)and promote rational clinical drug use.Methods 120 reports of ADR were analyzed.Results There were 30 kinds of medicine involved with ADR.Among these medicines,the Anti-infectives ranked the first and Chinese traditional medicine was on the second.And Intravenous injection brought 95 cases of ADR.Both skin rashes,itching and other skin damage including its annex injures were the main clinical manifestations of ADR,the injuries of digestive system come next.Conclusion In order to avoid and reduce the occurrence of adverse drug reactions,the rational usage of drugs should be noted. Key words: Adverse Drug Reaction(ADR); Rational drug use; Anti-infectives; Damage the skin and its annexes