Computer-assisted prediction of pesticide substructure using mass spectra

Mass spectral classifiers of 16 substructures that are present in basic structures of pesticides have been investigated to assist pesticide residues analysis as well as screening of pesticide lead compounds. Mass spectral data are first transformed into 396 features, and then Genetic Algorithm-Partial Least Squares (GA-PLS) as a feature selection method and Support Vector Machine (SVM) as a validation method are implemented together to get an optimization feature set for each substructure. At last, a statistical method which is AdaBoost algorithm combined with Classification and Regression Tree (AdaBoost-CART) is trained to predict the 16 substructures presence/absence using the optimization mass spectral feature set. It is demonstrated that the optimum feature sets can be used to predict the 16 pesticide substructures presence/absence with mostly 85-100% in recognition success rate instead of the original 396 features.     

Computer-assisted protein domain boundary prediction using the DomPred server

Domain prediction from sequence is a particularly challenging task, and currently, a large variety of different methodologies are employed to tackle the task. Here we try to classify these diverse approaches into a number of broad categories. Completely automatic domain prediction from sequence alone is currently fraught with problems, but this should not be so surprising since human experts currently have significant disagreement on domain assignment even when given the structures. It can be argued that we should only test the domain prediction methods on benchmark data that human experts agree upon and this is the approach we take in this paper. Even for the data sets on which human experts agree, automatic structure-based domain assignment still cannot always agree, and so again it is still unlikely that domain prediction methods will reliably obtain correct results completely automatically. We make the argument that computer-assisted domain prediction is a more achievable goal. With this aim in mind, we present the DomPred server. This server provides the user with the results from two completely different categories of method (DPS and DomSSEA). In this paper, each method is individually benchmarked against one of the latest domain prediction benchmarks to provide information about their respective reliabilities. A variety of different benchmark scores are employed since the accuracy of a domain prediction method depends critically on what types of results one wishes to obtain (single/multi-domain classification, domain number, residue linker positions, etc.). Also both of these methods, implemented within the DomPred server, can suggest alternative domain predictions, allowing the user to make the final decision based on these results and applying their own background knowledge to the problem. The DomPred server is available from the URL:http://bioinf.cs.ucl.ac.uk/software.html.     

Structures for controlling synthesis design and reaction modelling via knowledge acquisition

The performance of programs for computer-assisted organic synthesis (CAOS) is directly related to the knowledge base and to the procedures for deciding how the knowledge base should be used. The architecture of a knowledge base (text base, data base, rule base, model base and commonsense base) is discussed. The problem of knowledge acquisition is described with regard to pruning the productivity of CAOS systems. The commercial program 1stCLASS (for symbolic processing) is used with the SAAO (devised here for numeric processing) to form a commonsense base. For this purpose, knowledge was acquired by induction from the solutions provided by human experts to given problems. The general procedure is applied to the recognition of reaction sites which are crucial in the simulation of organic reactions.     

Computer-assisted prediction of small peptide sequencing in reversed-phase liquid chromatography

Summary A computer-assisted prediction system for small peptide sequencing has been constructed based on the retention prediction approach in reversed-phase liquid chromatography. The system has the basic function to predict retention of small peptides at any chromatographic conditions and this function can be useful for the prediction of sequencing. The outline of the system construction and the performance is discussed.     

Computer-assisted bilateral solution of chemical problems and generation of reaction networks

The theory of the bond/electron and reaction matrices, a mathematical model of the logical structure of constitutional chemistry, serves as the basis of a new generation of strictly logic-oriented programs for the solution of a variety of chemical problems without the use of any detailed empirical chemical information. These programs are interactive, have comfortable usermenus, and are implemented under the operating system MS-DOS on an IBM-compatible personal computer. The first representatives of the new generation are an improved version of IGOR (interactive generation of organic reactions) which “invents” chemical structures and reactions, and RAIN (reaction and intermediates networks) which generates, in a bilateral approach, pathways of chemical reactions and sequences of reactions from their given starting materials and products.     

The first stereoselective total synthesis of lankanolide. Part 1: Computer-assisted design and lactonization of model seco-acid derivatives

To design easily cyclizable seco-acid derivatives of lankanolide, the conformation of several model seco-acids was calculated and the lactonization experiments of the seco-acids were carried out to elucidate the efficiency of the cyclization of the model seco-acid.     

Computer-assisted retention prediction system in reversed-phase HPLC for O-ethyl O-aryl N-isopropyl phosphoramidothioates

A computer-assisted retention prediction system (RPS) of fifteen O-ethyl O-aryl N-isopropyl phosphoramidothioates ( 1 ) in reversed-phase HPLC was investigated. The system is based on the use of four physicochemical parameters (hydrophobicity II, electric effect σ, field effect F and steric effect E_s) which is closely related to the retention mechanism in reversed-phase HPLC. The system was evaluated by comparing the measured retention data with the predicted ones. The predicted values were consistent with the measured values within a relative error of 11.5%.     

Microwave in glycosylation reaction: design,and synthesis of highly substituted nicotinonitrile nucleosides

An efficient and rapid regiospecific approach for the synthesis of cyclic and acyclic nucleosides of 2-oxonicotinonitriles was performed. Whereas, glycosylation of 2-oxonicotinonitriles 1a, b with peracetylated sugars (namely, peracetylated glucose, galactose and ribose) under MWI tolerated exclusively the desired N-nucleosides 2a, b, 4a, b and 6a, b in significant yields (75–86%) and in short reaction time (5–7 min.). The same products were obtained under the conventional conditions, using halo-sugar with low yields in hard conditions. Similarly, the acyclic nucleosides 8a, b and 9a, b were obtained under MWI and conventional conditions via reaction of 1a, b with 4-bromo butyl acetate and 2-acetoxyethoxymethyl bromide. Finally, deprotection of the latter blocked N-nucleosides was performed via treatment with aqueous methanolic solution containing a catalytic amount of triethyl amine to give the desired free nucleosides 3a, b, 5a, b, 7a, b, 10a, b and 11a, b, respectively. The free nucleosides (3a, b, 5a, b, 7a, b and 11a, b) were evaluated against Gram (+?ve) bacteria, Gram (–ve) bacteria and one pathogenic Fungi namely, Aspergillus flavus. Good results were obtained for compounds 7a, b and 11a, b compared with the used standard drugs (Cefotaxime and Dermatin).

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Computer-assisted design and lactonization of model seco-acid derivatives of lankanolide

In some cases, seco-acid derivatives (a precursor of macrolactone) did not cyclize to form the corresponding macrolactone. To design easily cyclizable seco-acid derivatives of lanaknolide, the conformation of several model seco-acids was calculated, and lactonization experiments of the seco-acids prepared from oleandomycin were carried out to elucidate the efficiency of the cyclization of the model seco-acid. The easily cyclable seco-acid was designed to be C8 exomethylene derivative of lankanolide seco-acid. On the other hand, seco-acid derivative having tertiary alcohol at C8 was predicted not to cyclize to form macrolactone.     

Computer-assisted design of asymmetric 1,3-dipolar cycloadditions between dimethylvinylborane and chiral nitrones

This report describes a theoretical study of the 1,3-dipolar cycloadditions between dimethylvinylborane and different chiral nitrones, aimed at identifying the requisite structural features to achieve high levels of selectivity. Excellent regioselectivities towards the formation of the 5-borylisoxazolidines are computed in all cases due to the presence of a strong secondary orbital interaction between the boron of the vinylborane and the oxygen of the nitrones. While these transition structures show [3+3] character, 4-boryl regioisomeric structures have classical [3+2] character with weak carbon-boron secondary orbital interactions. Endo transition structures leading to the favoured products adopt chair-like conformations only, unlike their exo counterparts, which exhibit either boat or twist-boat structures. Placing a stereocentre adjacent to the nitrone nitrogen appears to be an effective strategy to stereodiscriminate the anti and syn approaches of the dipolarophile.     

Computer-assisted optimization of HPLC with post-column reaction for the determination of amino-acids

Computer-assisted optimization of a high-performance liquid chromatograph and associated post-column reactor is reported for the determination of six amino-acids. First six, then seven, experimental variables were considered. Non-standard experimental conditions were found which gave significantly improved colour development in the ninhydrin reaction. The composite modified simplex method for experimental optimization and a novel system-response function facilitated rapid and simultaneous improvement of separation, sensitivity and analysis time. The approach described is directly applicable to many similar systems.     

ROBIA: a reaction prediction program

A reaction prediction program, ROBIA, has been developed. This interactive computer program predicts the products of organic reactions from the starting materials and the reaction conditions, on the basis of the selected transformations within its database. This mechanistic approach generates a large number of products, from which the most important are selected using filters and molecular modeling calculations. The procedure has been applied to the possible biosynthesis pathway of dolabriferol. [reaction: see text]     

Computer-assisted prediction of antioxidant activities and toxicities of ionol, 5-hydroxy-6-methyluracil, and their derivatives

A mathematical model for prediction of antioxidant activity (AOA) with a recognition level of ∼90% was developed using the SARD-21 computer system. Based on this model, structural modification of ionol and 5-hydroxy-6-methyluracil was carried out. A set including 32 potential antioxidants was generated. The interval levels of toxicity were theoretically predicted and the effect of structural fragments on the toxic properties of the most efficient potential antioxidants was analyzed. Structural attributes characteristic of highly efficient, low-toxicity antioxidants were revealed for the first time. Based on complex analyses of the AOA and toxicity, thirteen structures of potentially efficient low-toxicity antioxidants were proposed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1274–1279, August, 2006.     

Computer-assisted generation of chemical reaction networks. Applications in mechanistic studies of organometallic catalysis

The Chem Net computer program designed for mechanistic studies of organic reactions occurring in solutions of metal complexes and on the surface of heterogeneous catalysts is proposed. The use of the program is illustrated by applications to catalyzed homogeneous hydrocarboxylation and hydroformylation of ethylene and heterogeneous hydrogenolysis of ethane. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp 1891–1898, October, 1999.     

Atropisomeric phosphinines: design and synthesis

The first atropisomeric phosphinine was designed and prepared by introducing substituents into specific positions of the heterocyclic framework; the presence of axial chirality was predicted by means of DFT calculations and experimentally verified by chiral HPLC analysis, derivatization experiments as well as temperature dependent 31P{1H} NMR spectroscopy.     

Computer-assisted structure elucidation

Summary Program CASE, an evolving computer model of the structure elucidation process, treats three major tasks: reduction of the chemical and spectral properties of a compound of unknown structure to their structural implications, generation of all complete molecular structures compatible with the structural features identified, and ranking these structures on the basis of the degree of fit between predicted and observed spectral properties. The current program status is described and program application is illustrated.

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Strukturaufklärung mit Computer-Hilfe

Zusammenfassung Ein in Entwicklung befindliches Computer-Modell (program CASE) wird beschrieben, das hauptsächlich folgende drei Aufgaben erfüllt: Zuordnung der chemischen und spektralen Eigenschaften einer Verbindung unbekannter Struktur zu ihren strukturellen Bedeutungen; Aufstellung aller Strukturen, die mit den gefundenen Eigenschaften im Einklang stehen; Einordnung dieser Strukturen je nach Übereinstimmung mit den vorhergesagten und gefundenen Parametern. Der derzeitige Entwicklungsstand des Programms wird erläutert und die Anwendung diskutiert.

     

Catalytic synthesis of thiazolidines by the reaction of Nef-isocyanide reaction

Research on Chemical Intermediates - A practical and efficient method for the synthesis of thiazolidine derivatives via Nef-isocyanide three-component reaction using supported phosphoric acid on...