Alexander V. Yarkov

CheD: Chemical Database Compilation Tool, Internet Server, and Client for SQL Servers

An efficient program, which runs on a personal computer, for the storage, retrieval, and processing of chemical information, is presented, The program can work both as a stand-alone application or in conjunction with a specifically written Web server application or with some standard SQL servers, e.g., Oracle, Interbase, and MS SQL. New types of data fields are introduced, e.g., arrays for spectral information storage, HTML and database links, and user-defined functions. CheD has an open architecture; thus, custom data types, controls, and services may be added. A WWW server application for chemical data retrieval features an easy and user-friendly installation on Windows NT or 95 platforms.

WinDat: An NMR Database Compilation Tool, User Interface, and Spectrum Libraries for Personal Computers

ion of literature data and/or documentation of laboratory results with the capability of searching for and predicting spectra. Here we describe WinDat,6 the outstanding features of which are extensive automated checking of input data, particularly the correct assignments of chemical shifts and JJ coupling constants, to support abstraction/documentation (since experience shows this to be a critical step as errors made at this time are very difficult to correct later) and a compilation of over 100 000 spectra of different nuclei.

A Java Chemical Structure Editor Supporting the Modular Chemical Descriptor Language (MCDL)

A compact Modular Chemical Descriptor Language (MCDL) chemical structure editor (Java applet) is described. The small size (approximately 200 KB) of the applet allows its use to display and edit chemical structures in various Internet applications. The editor supports the MCDL format, in which structures are presented in compact canonical form and is capable of restoring bond orders as well as of managing atom and bond drawing overlap. A small database of cage and large cyclic fragment is used for optimal representation of difficult-to-draw molecules. The improved algorithm of the structure diagram generation can be used for other chemical notations that lack atomic coordinates (SMILES, InChI).

Modular Chemical Descriptor Language (MCDL): Stereochemical modules

BackgroundIn our previous papers we introduced the Modular Chemical Descriptor Language (MCDL) for providing a linear representation of chemical information. A subsequent development was the MCDL Java Chemical Structure Editor which is capable of drawing chemical structures from linear representations and generating MCDL descriptors from structures.ResultsIn this paper we present MCDL modules and accompanying software that incorporate unique representation of molecular stereochemistry based on Cahn-Ingold-Prelog and Fischer ideas in constructing stereoisomer descriptors. The paper also contains additional discussions regarding canonical representation of stereochemical isomers, and brief algorithm descriptions of the open source LINDES, Java applet, and Open Babel MCDL processing module software packages.ConclusionsTesting of the upgraded MCDL Java Chemical Structure Editor on compounds taken from several large and diverse chemical databases demonstrated satisfactory performance for storage and processing of stereochemical information in MCDL format.

Hierarchical Clustering of Large Databases and Classification of Antibiotics at High Noise Levels

Abstract: A new algorithm for divisive hierarchical clustering of chemical compounds based on 2D structural fragments is suggested. The algorithm is deterministic, and given a random ordering of the input, will always give the same clustering and can process a database up to 2 million records on a standard PC. The algorithm was used for classification of 1,183 antibiotics mixed with 999,994 random chemical structures. Similarity threshold, at which best separation of active and non active compounds took place, was estimated as 0.6. 85.7% of the antibiotics were successfully classified at this threshold with 0.4% of inaccurate compounds. A .sdf file was created with the probe molecules for clustering of external databases. Keywords: Molecular structure, hierarchical clustering, algorithm, classification of antibiotics 1. Introduction The problem of clustering can be defined as follows. The given N data points in a D -dimensional space should be organized into K clusters. Data points from one cluster should have more similarities than those from different clusters. Clustering algorithms can be classified as partition algorithms and hierarchical ones [1]. Partition algorithms are fast and require small memory. K-mean clustering is an example of a partition algorithm [2,3]. Hierarchical algorithms combine agglomerative and divisive algorithms. Generally, hierarchical algorithms are quite demonstrative. Agglomerative algorithms are

SiO2 aerogels modified by perfluoro acid amides: a precisely controlled hydrophobicity

Five series of novel fluorinated aerogels based on acylated (3-aminopropyl)trimethoxysilane (APTMS) (MeO)3Si(CH2)3NHC(O)RF (RF = CF3, C2F5, CF3CF(OCH3), C6F13 and C8F17) were prepared by a sol–gel method followed by supercritical drying in four different solvents, including isopropanol, CO2, methyl tert-butyl ether (MTBE) and hexafluoroisopropyl alcohol (HFIP). The hydrophobicity of the aerogels was shown to increase smoothly with the increase in the length of the fluorinated substituent – the water drop contact angle θ changed from 0° and reached 143° for isopropanol dried samples, 133° for CO2 dried samples, 136° for MTBE dried samples, and ∼140° for HFIP dried samples. The results obtained provide an easy method for the preparation of aerogels with precisely controlled hydrophobicity.

VIBRATIONAL SPECTRA AND NORMAL COORDINATE ANALYSIS OF 4,13-DIAZA-18-CROWN-6-CALCIUM CHLORIDE AND BROMIDE COMPLEXES

Abstract Calcium chloride (40CaCl2 and 44CaCl2) and bromide (40CaBr2) complexes of 4,13-diaza-18-crown-6 (DA-18C6) were investigated using IR and Raman spectroscopy and normal coordinate analysis (NCA). Calcium isotopic substitution was used to determine the valence force field of the DA–18C6–CaCl2 complex (C2h symmetry). Practically no change in the vibrations of the macrocyclic ligand were observed upon complex formation, indicating the absence of conformational distortion.

Physicochemical property profile for brain permeability: comparative study by different approaches

Abstract A comparative study of classification models of brain penetration by different approaches was carried out on a training set of 1000 chemicals and drugs, and an external test set of 100 drugs. Ten approaches were applied in this work: seven medicinal chemistry approaches (including “rule of 5” and multiparameter optimization) and also three SAR techniques: logistic regression (LR), random forest (RF) and support vector machine (SVM). Forty-one different medicinal chemistry descriptors representing diverse physicochemical properties were used in this work. Medicinal chemistry approaches based on the intuitive estimation of preference zones of CNS or non-CNS chemicals, with different rules and scoring functions, yield unbalanced models with poor classification accuracy. RF and SVM methods yielded 82% and 84% classification accuracy respectively for the external test set. LR was also successful in CNS/non-CNS (denoted in this study as CNS+/CNS−) classification and yielded an overall accuracy equivalent to that of SVM and RF. At the same time, LR is especially valuable for medicinal chemists because of its simplicity and the possibility of clear mechanistic interpretation.

Classification (Agonist/Antagonist) and Regression “Structure-Activity” Models of Drug Interaction with 5-HT6

One promising target for novel psychotropic drugs is the 5-HT6 receptor, G-protein-coupled receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked pro-cognitive effects. An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models. The present study is devoted to a detailed QSAR analysis of 61 drugs (26 agonists and 35 antagonists) acting on the 5-HT6 receptor (rattus norvegicus and homo sapiens). Five classification methods were used: k-Nearest Neighbors (k-NN), Logistic Regression (LG), Linear Discriminant Analysis (LDA), Random Forest (RF), and Support Vector Machine (SVM). Multiple Regression Analysis (MRA) was involved also for regression analysis. Spectra of Inter Atomic Interactions (SIAI) were applied in the search for ligand centres interacting with the 5-HT6 receptor. SAR and QSAR models based on the use of HYBOT, MOLTRA, VolSurf+, and SYBYL programs, and having cross-validated coefficients of determination of at least 0.80, show a predominant influence of H-bond acceptor ability and hydrophobicity on the type of ligand activity and degree of inhibition.