摘要:

AbstractThis work demonstrated that descriptors of soft electrophilicity for aromatic chemicals such as average superdelocalizability and LUMO energy could be used together with the hydrophobicity descriptor, log P, to explain the variation of acute toxicity of substituted benzenes, phenols, and anilines to fish. The hydrophobicity and soft electrophilicity descriptors were shown to be orthogonal for the 114 chemicals studied. For proelectrophiles, the structure‐toxicity relationships accurately predict toxicity when the stereoelectronic parameters were computed for the metabolic activation products. The QSAR for acute toxicity using these molecular descriptors defines a toxicity plane which includes several modes of toxic action.Type (I) narcotics are chemicals located in the region of low reactivity where toxicity varies with hydrophobicity alone. Type (II) narcotics are more toxic than type (I) narcotics at similar values of log P, and the increase can be explained by stronger electronic interactions with cellular soft nucleophiles. Highly reactive soft electrophiles which have dissociating protons such as 2,4,‐dinitrophenol produce symptoms of respiratory uncouplers. Those without dissociating protons produce symptoms of reactive toxicity consistent with covalent bind

ISSN:0931-8771    

DOI:10.1002/qsar.19930120402

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThe chemical reactivity toward 4‐nitrobenzylpyridine (4‐NBP) of a series of twelve mono‐, di‐ and trisubstituted epoxides has been modelled by means of multivariate quantitative structure‐property relationships (QSPRs). The models were established using theoretical descriptor variables and partial least squares (PLS) analysis. It was found that a multivariate set of eleven descriptor variables was sufficient to adequately model the chemical reactivity. Furthermore, there existed a non‐linear relationship between the theoretical descriptors and the chemical reactivity. Two‐component PLS models were generally required, using the second component to compensate for non‐linearity in the first. The nature of the non‐linearity suggests that different physico‐chemical factors are regulating the chemical reactivity among two observed subgroups of epoxides. The reactivity of one group of five epoxides with one non‐substituted ring carbon is regulated by the electronegative properties of the substituent on the other ring carbon, whereas the reactivity of seven di‐ and trisubstituted epoxides depends on a combination of the substitution pattern around the epoxide ringandthe size of these substituents. Two additional points of general relevance for QSPR modelling are also addressed, namely predictor variable selection and appropriate transformation of

ISSN:0931-8771    

DOI:10.1002/qsar.19930120403

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThis note presents the multiconformational MTD method and its application in a QSAR for acetylcholinesterase catalysed hydrolysis rates of a series of 25 acetic acid esters. Multiconformational MTD allows consideration of molecules with several low energy conformations, as the mostly aliphatic alcohol esters of this series, for QSAR. Conformations were selected for the QSAR study according to their energies calculated by the COSMIC modelling program. Information from an X‐ray crystallography study, together with results of conformational energy calculations was used in constructing the hypermolecule for the 25 acetic acid ester molecules. A classical Hansch QSAR, with σ*‐Taft constants, π‐hydrophobicities and Es‐steric constants yields r2= 0.779 and r2cv = 0.577 in a crossvalidation procedure. The multiconformational MTD, with σ* and MTD as structural parameters yields, for the corelational equation r2= 0.868 and r2cv = 0.661 in a cross validation procedure. Both correlational equations indicate an appreciable positive effect of electron withdrawing ester groups. The optimised receptor map indicates a receptor cavity with certain similarities to acetylcholine, but somewhat larger. QSAR studies are able, thus, to yield supplementary details to those given by X

ISSN:0931-8771    

DOI:10.1002/qsar.19930120404

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThe influence of large substituents in o‐, m‐ and p‐positions of the phenyl ring of isomeric 3‐, 4‐ and 5‐sulfanilamido‐1‐phenylpyrazoles on their inhibitory effect againstE.coliderived dihydropteroic acid synthase and whole cellE.colihas been studied. According to their pKa values, the 3‐ and 5‐series show high antibacterial activity while the 4‐series displays feeble inhibitory activity. In the 3‐series the variation in MIC is explained by differences in pKa (Hammett σ) and molecular weight (MW) or substituent surface respectively, whereas in the 5‐series steric effects of substituents in the o‐position of the 1‐phenyl ring and MW describe the differences in whole cell activity. In the cell‐free system the inhibitory activity depends for the 3‐series solely on pKa or Hammett σ, respectively, and in the 5‐series, where the derivatives are almost completely ionized, the variation is solely explainable by the steric effect of the substituents in o‐position. The steric effect of o‐substituents in the 5‐series has been studied and explained by NMR‐ and molecular modelling techniques. The observed differences in electronic effects of substituents comparing the 3‐ and 4‐series with the 5‐series could be explai

ISSN:0931-8771    

DOI:10.1002/qsar.19930120405

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThe concept of the generation of molecular structures directly from a QSAR equation using topological indices is presented. The equations relating the path counts to the graph atom degree counts is presented as a linkage in the flow of information. The multiple candidate molecules are derived from target indices using a quality QSAR equation. An example is developed to illustrate the process using molecular connectivity indices.

ISSN:0931-8771    

DOI:10.1002/qsar.19930120406

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractElectron affinity for a wide range of organic molecules was calculated from molecular structure using the chemical reactivity models developed in SPARC. These models are based on fundamental chemical structure theory applied to the prediction of chemical reactivities for organic molecules strictly from molecular structure. The energy differences between the LUMO state and the HOMO state for a molecule of interest are factored into mechanistic components including the field, sigma induction and resonance contributions to these energy differences. The RMS deviation between observed and calculated electron affinities was found to be less than 0.14 e.v. for a large set of organic molecules.

ISSN:0931-8771    

DOI:10.1002/qsar.19930120407

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThis paper demonstrates that the computation of Euclidian distances between objects generates an intrinsic geometry, which, besides containing all the information explicitly present in the original space, also provides new information about the object interrelationships. In other words, by computing distances the data are mapped onto a new, and more flexible, reference frame. Such properties of the distance function also permit the derivation of non linear descriptors of the data space, and can be usefully exploited for pattern recognition purposes. In particular, it is demonstrated that this approach is able to separate embedded classes, which have been repeatedly reported in QSAR research.

ISSN:0931-8771    

DOI:10.1002/qsar.19930120408

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19930120409

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19930120410

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19930120411

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY