bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regularities of the Partition Coefficients of Bis, Tris, and Tetrakis(acetylacetonato)metal (II, III and IV) Complexes
Authors: Watarai Hitoshi , Oshima Hideo , Suzuki Nobuo 
Published: October 2006

AbstractThe partition coefficients of seven acetylacetonato complexes, Pt(acac)2, Pd(acac)2, Be(acac)2, VO(acac)2, Cr(acac)3, Al(acac)3 and Co(acac)3 and those of trifluoroacetylacetone (Htfa) and Be(tfa)2 were determined at 25°C employing dodecane, carbon tetrachloride, and/or benzene as an organic phase. The molar volumes of acetylacetonato complexes which include bis, tris and tetrakis complexes were also determined from precise density measurement at 25°C. Linear correlations between the partition coefficients of acetylacetone (enol form) and those of the bis, tris, and tetrakis complexes which include some available literature data were obtained, and interpreted in the frame of the modified regular solution equation which has a binary coefficient introduced to improve the simple geometric mean assumption. On the main factor governing the partition equilibrium, a general importance of cavity formation energy was concluded by comparison with the scaled particle calculation. Hydration in the bis complexes was suggested as an additional factor to govern partition coefficient.
Biological Receptor Maps. 1 Steric Maps. The SIBIS Method
Authors: Motoc Ioan 
Published: October 2006

AbstractThe SIBIS method for calculating the topographical steric map of biological receptor is described in detail. SIBIS is a self‐consistent type algorithm based upon a reference structure and which is well suited to delineate the main steric features of the receptor. Since the application of the method is not restricted to structurally congeneric molecules, the resultant steric map offers the linkage information to coanalyze structurally different compounds exhibiting common biological action. The molecular structure descriptor vector used in SIBIS permits the development of a simple method for quantitatively comparing the degree of relatedness of the shape of bio‐organic molecules exhibiting the same biological action but which may vary widely in their shape.
Structural Requirements for the Membrane Damaging Effect of Non Homologous Series of Nonionic Tenzides. Structural Requirements for the Biological Activity of Tenzides
Authors: Cserháti Tibor , Szőgyi Maria , Bordás Barna , Dobrovolszky András 
Published: October 2006

AbstractThe lipophilicity and the membrane damaging effect responsible for microbicidal activity of 26 nonionic tenzides belonging to various homologous series have been determined by reversed‐phase thin‐layer chromatography and by permeability measurements on dipalmitoyl‐phosphatidyl‐choline liposomes respectively. The lipophilicity correlated significantly to the membrane damaging effect, however it explained only about 35% of the total variance. Stepwise regression analysis showed that the requirements for the membrane disorganization are the presence of a bulky hydrophobic part to be built in to the hydrophobic alkyl chains of fatty acids and the optimum number (6–13) of ethylene‐oxide groups per molecule. Tenzides with too short ethylene‐oxide chains are buried in the lipid bilayer, the long ethylene‐oxide chains do not modify the membrane permeability.
Predictive Power of Robust Regression Applied to QSAR Studies
Authors: Moriguchi Ikuo , Komatsu Katsuichiro , Matsushita Yasuo 
Published: October 2006

AbstractRobust regression methods were applied to 56 sets of structure‐activity data collected from the literature. The methods included the Huber estimator, the sine estimator, the biweight estimator, and least‐squares with a cut‐off option. On the basis of the kurtosis (Ku) for the error distribution of ordinary least‐squares (OLS) regression, the data sets were classified into two groups: 26 sets with Ku > 0, i.e., with thick‐tailed error distribution (Group A) and 30 sets with Ku < 0 (Group B). The predictive powers of the robust methods and OLS were compared by means of the leave‐one‐out technique. The robust methods generally produced greater correlation coefficients between observed and predicted activities than OLS for the sets of Group A, but the differences were not significant in the majority of cases, e.g., 17 of the 26 sets by use of the sine estimator. For Group B, the predictive results of the robust methods were comparable or rather inferior to those of OLS. It may be concluded that OLS does as well as robust techniques in most cases, and that the adoption of the complicated robust techniques is not warranted in QSAR studies except under extreme circumstances.
Chemometric Investigation of Antitumor Tests
Authors: Ebert Cynthia , Lassiani Lucia , Linda Paolo , Nisi Carlo , Alunni Sergio , Clementi Sergio 
Published: October 2006

AbstractThis study was aimed to investigate by principal components analysis, the information content of various routine antitumor tests collected on a series of p‐substituted aryldimethyltriazenes.The results permit to detect that the effective doses, expressed as log T/C, are a measure better than the predetermined activity levels for stating the selective antimetastatic properties of these compounds.In this respect, PCA appear to be more suitable then MRA in describing the data set.
The Application of the PHL Concept to QSAR: Detection of Data Deficiencies Cross Validation, Detection of Alien Effects
Authors: Mager Harry 
Published: October 2006

AbstractCross‐validation methods in which a portion of the data is used to estimate the model coefficients, and the remainder of the data is used to measure the prediction accuracy of the model are of outstanding significance in QSAR work.The concept of data points with high leverage (PHL) based on leave‐one‐out estimates (LOO) is introduced to quantitative drug design. A new measure is derived allowing to judge the stability of the individual regression coefficients against sample structure variation. Furthermore, it seems to be possible to examine to which extent the coefficient for the physicochemical property xk(e.g. π) is influenced by special values of the physical property xj(e.g. Es), which allows to detect “alien effects”.The procedure is applied to 7‐substituted 4‐hydroxyquino‐line‐carboxylic acids inhibiting respiration of Ehrlich ascites cells.
The Anesthetic Activity and Toxicity of Halogenated Ethyl Methyl Ethers, a Multivariate QSAR Modelled by PLS
Authors: Hellberg Sven , Wold Svante , Dunn William J. , Gasteiger Johann , Hatchings Michael G. 
Published: October 2006

AbstractQSAR between anesthetic activity, toxicity, and a multi‐variate set of structural descriptors for a series of halogenated ethyl methyl ethers were analysed by the method of partial least squares in latent variables (PLS). A two dimensional model resulted describing 86% of the variance in anesthetic activity. A three dimensional model describes 87% of the variance in toxicity. A grouping of anesthetics according to their type of side effects was indicated by the data analysis.
Topological Pharmacophores New Methods and Their Application to a Set of Antimalarials Part 1: The Methods LOGANA and LOCON
Authors: Streich Wolf Jürgen , Franke Rainer 
Published: October 2006

AbstractTopological pharmacophores are two‐dimensional substructural patterns characteristic of compounds possessing a desired biological property (e.g., high activity) while absent from compounds devoid of this property. Two new methods for the evaluation of such pharmacophores, LOGANA and LOCON, are presented which are both designed in such a way that full use can be made of the data handling capacity of computers while maintaining an optimal impact of the professional skill and experience of medicinal chemists with no special mathematical knowledge required. Both methods are based on the stepwise combination of substructural descriptors by means of the logical operations “and”, “or” and “not”. No assumptions about additivity of effects, linear models or the validity of certain statistical formalisms are necessary. While LOGANA deals with biological data in the form of classifications LOCON can be applied to activity data on a continuous scale. The advantages and limitations of the two methods are discussed.
Distinguishing Atom Differences in a Molecular Graph Shape Index
Authors: Kier Lemont B. 
Published: October 2006

AbstractThe molecular shape index, previously described, has been extended to take into account the size differences among heteroatoms and carbon atoms in different valence states. In the algorithm for the shape index, 2K, calculated as a function of the non‐hydrogen atom count, the count value of non‐C sp3 atoms is modified by a term α. The value of α is derived from the covalent radius of an atom relative to the radius of C sp3. Several examples of the use of the atom‐specified shape index, 2Kα, in biological studies are presented.
Quantitative Structure‐Activity Relationships on MAO Substrates by Means of Quantum Chemical Properties
Authors: Sanz F. , Martiń M. , Lapeña F. , Manaut F. 
Published: October 2006

AbstractThe structural and electrostatic requirements for the two types of monoamine oxidase (MAO) activity are quantitatively studied using similarity coefficients between the electron density and the molecular electrostatic potential (MEP) distributions of a set of substrates.For the comparison of electron density distributions, the RXY similarity coefficient is used. In the case of MEP a new similarity coefficient is defined.Correlations between these coefficients and the experimental activities are studied and the results are consistent with previous ones. This shows the interest of this two parameters in QSAR studies.
Chance Factors in Nonparametric Linear Discriminant Studies
Authors: Stouch Terry R. , Jurs Peter C. 
Published: October 2006

AbstractStudies were performed to determine if the screening of large pools of prospective variables could lead to fortuitous improvements in the classification success rates provided by nonparametric linear discriminants. These studies parallel earlier work by Topliss and Edwards on regression analysis. It was found that fortuitous increases do occur, but could probably be kept low if the number of examined variables is kept below one‐half the number of observations.
Structure‐Molar Refraction Relationships of Alkylsilanes Using Empirically‐Modified First Order Molecular Connectivity Indices
Authors: Kupchik Eugene J. 
Published: October 2006

AbstractTwo empirically‐modified first order molecular connectivity indices, which reflect either the larger covalent radius of silicon compared to carbon or the longer silicon‐carbon bond length compared to the carbon‐carbon bond length, were calculated for 115 alkylsilanes. The correlation of molar refraction with these empirically‐modified first order molecular connectivity indices was found to be excellent. It is shown that these empirically‐modified molecular connectivity indices give a significantly more satisfactory prediction of molar refraction for a mixed set of alkanes and alkylsilanes than does the simple first order molecular connectivity index or the first order molecular connectivity index derived from molar refraction data.
Three‐Dimensional Quantitative Structure‐Activity Relationships I. General Approach to the Pharmacophore Model Validation
Authors: Motoc Ioan , Dammkoehler Richard A. , Mayer Dorica , Labanowski Jan 
Published: October 2006

AbstractA conceptually and computationally integrated approach to pharmacophore model validation is discussed at length. It allows one, for the first time, to address the question of pharmacophore existence and assessment of its uniqueness in a rigorous and quantitative manner. The approach has been effectively applied to the analysis of seventeen structurally diverse potent inhibitors of angiotensin converting enzyme and the resultant pharmacophore greatly refines the previously suggested models.
Inclusion of Symmetry as a Shape Attribute in Kappa Index Analysis
Authors: Kier Lemont B. 
Published: October 2006

AbstractThe molecular shape attribute of symmetry is introduced as a supplement to the shape attributes encoded by the kappa values. This attribute is indexed by the Shannon equation for information content and is designated as 0κ within the framework of multiple path, path and atom counts to derive the kappa values. A new procedure is introduced to calculate a label characterizing the uniqueness or equivalence of atoms in a molecule using the connection matrix. This label, called the relative topological state, is used in the Shannon equation to calculate the information content or 0κ. Two examples illustrate the utility of 0κ along with other kappa values to encode attributes of molecular shape influencing physical and biological properties.
Hydrophobic Properties of Chromones and Flavones. Relationships Between Octanol/Water Partition Coefficients and RP‐HPLC Capacity Factors
Authors: Recanatini Maurizio 
Published: October 2006

AbstractThe octanol/water partition coefficient (P) and the RP‐HPLC capacity factors (k′) at four different concentrations of organic modifier (methanol) in the mobile phase have been measured. The observed log P values of the polar substituted compounds show good consistency, if the interactions among the polar groups are taken into account on the basis of the Leo‐Fujita theory. Log P and log k′ are linearly correlated at the four methanol concentrations examined and at the extrapolated 0% methanol concentration. The phenolic compounds deviate from the correlation and this is recognized as a characteristic behaviour of the C‐18/ MeOH‐H2O chromatographic system.
A Substituent Steric Effect Index Based on the Molecular Graph
Authors: Kier Lemont B. 
Published: October 2006

AbstractThree graph‐based indexes of molecular shape have been found to correlate well with the Taft steric indexes, Es, for electron influence‐free alkyl groups and ten symmetric‐top groups used by Charton to compute a Van der Waals radius‐based index, v. The equation model includes the 1kα, and 3Kα, shape indexes and the 0k index equivalent to the Shannon information content per molecule. This later index encodes the group symmetry. The equation model is simplified to the expression ≈︁ = 2k ‐ 3kα ‐ 0k where Xi (≈︁) is proposed as a graph‐based shape index encoding the steric influence of a group.
Multivariate Characterization of Amino Acids by Reversed Phase High Pressure Liquid Chromatography
Authors: Skagerberg Bert , Sjöström Michael , Wold Svante 
Published: October 2006

AbstractThe twenty coded and four non coded amino acids were multivariately characterized by HPLC. The retention times for dansyl derivatives of the amino acids in nine eluents on a reversed phase C18 column were used.With the nine HPLC variables and five additional variables (molecular weight, pK‐COOH, pK‐NH2, pI and substituent van der Waals volume) comprizing the matrix X, two partial least squares projections to latent structures (PLS) models were developed for eighteen of the coded amino acids, with the previously developed principal properties (PP.s) z1 and z2 as single y‐variables. The PLS models described 90% and 87% of variance in z1 and z2 respectively. Values for z1 and z2 for the four non coded amino acids were predicted from their X‐data and the PLS models.
Systematic QSAR Procedures with Quantum Chemical Descriptors
Authors: Kikuchi Osamu 
Published: October 2006

AbstractSystematic QSAR procedures with quantum chemical descriptors were described by showing practical calculations on the inhibition of thiopurine methyltransferase by benzoic acid derivatives. In the QSAR analysis, a large number of descriptors relating to reactivity and interaction efficiency are handled, and the collinearities inherently involved among them should be removed to get the stable regression equations. Collinearity was detected by the A value which is the sum of the reciprocals of the eigenvalues of correlation matrix of descriptors divided by the number of descriptors in the equation. In the method of evaluation of all possible equations, the candidate equations selected on the basis of the correlation coefficient with activity and/or predicted sum of square should be examined one by one by the A testing. In the stepwise methods, noncollinear descriptor set is required. The collinearity between two descriptors was removed by a simple method, deleting one of the two descriptors whose correlation is large. It was recommended that the A testing routine was introduced into each step to find out multicollinearity.
Molecular Modelling of the Active Site of Enkephalin‐Degrading Neutral Endopeptidase‐24.11 (Enkephalinase) An Active Site Model for Neutral Endopeptidase‐24.11
Authors: Andrews Peter R. , Iskander Magdy N. , Issa John , Reiss James A. 
Published: October 2006

AbstractThe active site regions of thermolysin (TLN) and carboxypeptidase A (CPA) are directly compared by superimposition of the published crystal structures of eight TLN/inhibitor complexes and four CPA‐inhibitor complexes. There is a remarkable similarity in the S′1 region of these two zinc metalloenzymes, and it is suggested that this may be a common feature among other enzymes of this class, including the enkephalin‐degrading neutral endopeptidase or “enkephalinase” (NEP‐24.11). Assuming this common feature, the possible geometry of the S′2 region of enkephalinase was determined by performing classical potential energy calculations on potent NEP‐24.11 inhibitors. The active conformation of these inhibitors was thus identified as similar to that found in the X‐ray crystal structure of TLN/inhibitor complexes. It is proposed that the active site region of TLN should serve as a reasonable model for that of NEP‐24.11. Extension of the model to the case of angiotensin‐converting enzyme (ACE) showed that this enzyme might have a similar S′1 region to the other three enzymes, and allowed further definition of the ACE model previously developed in our laboratory.
Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies
Authors: Cramer Richard D. , Bunce Jeffrey D. , Patterson David E. , Frank Ildiko E. 
Published: October 2006

AbstractTo better evaluate, in the context of QSAR studies, new validation techniques such as bootstrapping and crossvalidation and the new analytic technique of partial least squares (PLS), seventeen QSAR results taken from nine recent publications were reexamined using these techniques. The results indicate that bootstrapping and crossvalidation are more powerful indicators of possible chance correlation than are the classical tests based on assumed normal independent distribution of variables. Although PLS will not detect all correlations existing within a set of data, its conservative behavior is particularly valuable when the candidate physicochemical descriptors are numerous and non‐orthogonal.
Structure — Molar Refraction Relationships of Alkylgermanes Using Molecular Connectivity
Authors: Kupchik Eugene J. 
Published: October 2006

AbstractCorrelation of molar refraction with the first order molecular connectivity index was found to be excellent for alkylgermanes of molecular formula GeCnH2n+4. The correlation was further improved by the use of either of two empirically‐modified first order molecular connectivity indices, which reflect either the larger covalent radius of germanium compared to carbon or the longer germanium‐carbon bond length compared to the carbon‐carbon bond length. Use of the empirically‐modified indices improves the prediction of molar refraction for a mixed set of alkanes and alkylgermanes and for a mixed set of alkanes, alkylsilanes, and alkylgermanes.
Hydrophobicity of Di‐ and Tripeptides Having Unionizable Side Chains and Correlation with Substituent and Structural Parameters
Authors: Akamatsu Miki , Yoshida Yohji , Nakamura Hideaki , Asao Masaaki , Iwamura Hajime , Fujita Toshio 
Published: October 2006

AbstractAfter establishing experimental conditions to obtain a reliable partition ratio, P', we measured the value of 59 di‐ and tripeptides composed of amino acids having unionizable side chains in a 1‐octanol/pH 7.0 aqueous phosphate buffer system in order to approximate the true partition coefficient. We then formulated an equation correlating the variations of log P' (pH 7) among peptides with free‐energy‐related physicochemical parameters for the side chain substituents and substructures. The log P' value of di‐ and tripeptides is governed by the sum of the hydrophobicity of the peptide backbone and side chains as well as by the steric effect of side chain substituents on the relative solvation of backbone and terminal functional groups. For peptides containing amino acids with polar side chains, the log P' value is higher than that predicted by these effects. The difference is larger as the polar heteroatom in side chains gets closer to the backbone. This may correspond to the “polar proximity factor” for reductions of hydrophilicity observed when polar groups are crowded together. For the side chain of serine and threonine, the difference is even higher than that expected by the polar proximity effect, presumably due to intramolecular hydrogen bond formation.
QSAR and Binding Model for Inhibition of Rat Liver Catechol‐O‐Methyl‐Transferase by 1,5‐Substituted‐3,4‐Dihydroxybenzenes
Authors: Taskinen Jyrki , Vidgren Jukka , Ovaska Martti , Backström Reijo , Pippuri Aino , Nissinen Erkki 
Published: October 2006

AbstractQuantitative structure‐activity analysis was carried out for in vitro inhibition of rat liver catechol‐O‐methyl‐transferase by a series of 1,5‐substituted‐3,4‐dihydroxybenzenes. Linear regression analysis showed high correlation of inhibitory activity with both empirical electronic substituent parameters and quantum chemical descriptors. The combined effect of both substituents on lowering the pKa values of catechol hydroxyls and the energy of the lowest unoccupied molecular orbital appeared to be the most important determinant of increasing activity. Both substituents seemed to be also directly involved in binding. Hydrophobicity of the substituent at position 1 and the electronic structure of the substituent at position 5 were correlated with activity. A model for binding interactions of inhibitors was postulated on the basis of the QSAR equations derived.
Electron Affinity/Radiosensitizing Activity Relationship for Quaternary 5‐Nitroimidazole Derivatives. Quantum Chemical QSAR
Authors: Santos Lucia , Pilar Cornago M. , Izquierdo M. Cruz , Consuelo Lopez‐Zumel M. , Smeyers Y. G. 
Published: October 2006

AbstractThe electron affinity of five new synthetised quaternary 5‐nitroimidazole derivatives was evaluated by means of quantum mechanical CNDO/S calculations and by polarographic measurements. The final aim of these evaluations was to correlate the electron affinity of the products with their previously tested radiosensitizing efficiencies, in order to elucidate the classification of these products as electroaffinic radiosensitizers, in the same way as many other nitroimidazole compounds. Results from both the experimental and theoretical methods give an equally good evaluation of the product electron affinity. An exponential correlation between the LUMO energy values of the neutral molecular structures and the cellular radiosensitizing efficiencies (D.M.F.) of the products was obtained; and this result enables these quaternary 5‐nitroimidazole derivatives to be classified as electroaffinic radiosensitizers.