摘要:

A comparison of several structure-property models for predicting the solubility of aliphatic alcohols in water is presented. Models based on the valence vertex-connectivity indices are better than models based on weighted edge-connectivity indices or vertex-connectivity indices or parameters related to the molecular surface area. Models based on ordered orthogonalized descriptors are better than models based on non-orthogonalized or orthogonalized descriptors. The best structure-solubility model is obtained with ordered orthogonalized descriptors which include the OH group.

ISSN:1062-936X    

DOI:10.1080/10629369808039152

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

The toxicity data of 256 chemicals tested in both the 96-hPimephales promelasmortality assay and the 2-dTetrahymena pyriformisgrowth inhibition assay were evaluated using quantitative structure-activity relationships (QSARs). Each chemical wasa prioriassigned a mode of action of either narcoses or soft electrophilicity. Narcoses were separated into nonpolar narcosis, polar narcosis, monoester narcosis, diester narcosis, amine narcosis, and weak acid respiratory uncoupling based on the presence or absence of specific toxicophores. Toxicity of each narcotic mechanism was initially regressed against the 1-octanol-water partition coefficient (logKow). The slopes of these logKowbased QSARs were observed to ascertain whether a relationship exists between the value of the slope and the reactivity of the mechanism of action. With both the fish and ciliate data nonpolar narcosis was the least reactive mechanism. It was followed by the other reversible narcoses. The soft electrophile mode was separated into the specific molecular mechanisms of:SN2reactors, Schiff-base formers, Michael-type addition, or proelectrophilicity (precursors to Michael-type addition chemicals). These mechanisms were represented structurally by the nitrobenzenes, aldehydes, polarizedα-βunsaturates (e.g., acrylates and methacrylates), and acetylenic alcohols, respectively. Electrophilic toxicity was not correlated with hydrophobicity. QSARs based on molecular orbital (MO) quantum chemical descriptors were used to improve the predictability of the electrophilic mechanisms. Relevant descriptors include average superdelocalizability (Snav) for the nucleophilic addition of the nitrobenzene; atomxandyacceptor superdelocalizability (Ax); and bond order (Bx-y) for the Michael-type addition of the acrylates; and logKowand atomxnet charge (Qx) for the Schiff-base forming aldehydes. The pertinent descriptors for proelectrophiles were logKowandSnav. Principal differences between the QSARs for the two biological endpoints were observed for the ester narcoses, proelectrophiles, and Schiff-base forming aldehydes.

ISSN:1062-936X    

DOI:10.1080/10629369808039153

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

It is known, more or less, how to create a QSAR model for predicting toxicological activities of one individual chemical not interfering with others. Combined chemical exposures are, however, rather the rule than an exception in workplaces and in the environment. Simultaneous or sequential exposures to two or more chemicals can change the toxicity of each chemical, both quantitatively and qualitatively. The resulting activities of mixtures may be additive, more often they are not.

ISSN:1062-936X    

DOI:10.1080/10629369808039154

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

A structure-activity relationship (SAR) of thein vitropercutaneous absorption of polycyclic aromatic hydrocarbons (PAH) is described. The data set consisted of 60 three to seven ring PAH. Over 50 numeric descriptors were generated from the modeled molecular structures. Computer aided methods were used to evaluate descriptors and develop linear expressions relating the percent of dermally applied PAH dose absorbed through skin (PADA) to PAH structure. Three regression models with one and two variables were developed. The log octanol/water partition coefficient (logP) was the most important variable in determining percutaneous absorption. An inverse relationship between logPand the skin penetration properties of the PAH was observed. Nearly 40 of 60 PAH tested had PADA-values within a factor of two of benzo[a]pyrene (BaP); well over 50 of 60 had PADA-values within a factor of three. The results lend support to the use of isotopically labeled BaP as a surrogate for measuring the dermal flux (in vivoandin vitro) and estimating the dermal bioavailability of PAH from complex mineral oil and coal-tar derived mixtures.

ISSN:1062-936X    

DOI:10.1080/10629369808039155

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

Comparative Molecular Field Analysis (CoMFA) was applied to a comprehensive data set of heterogeneous nitroaromatics tested inSalmonella typhimuriumTA98 and TA100 with and without S9 microsomal activation. The four CoMFA models developed agree with postulated mechanisms of mutagenicity, and explain over 70% of the corresponding mutagenic variance. The standard deviation coefficient contours common in the four models included high electronic density regions equivalent to C4-C5 in the pyrene ring, and an electron deficient site equivalent to C6. These areas are associated with high mutagenicity. Electron deficient areas may be related with the nitroreductive bioactivation of nitroaromatics. Electron rich sites may be involved with oxidative mechanisms analogous to the bioactivation pathway of polycyclic aromatic hydrocarbons. The contribution of steric factors to mutagenicity follows the order TA98 + S9 > TA98 > TA100 + S9 > TA100. The models indicated that increasing bulk perpendicular to the aromatic plane would decrease mutagenicity, but increasing the aromatic ring system along a region corresponding to C6-C7 in 1-nitropyrene would increase mutagenicity.

ISSN:1062-936X    

DOI:10.1080/10629369808039156

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

The relative toxicity (logIGC−150) of 49 selected aliphatic amines and aminoalkanols was evaluated in the staticTetrahymena pyriformispopulation growth impairment assay. Excess toxicity, indicated by potency greater than predicted for non-polar narcotic alkanols, was associated with both classes of test chemicals. Moreover, the aminoalkanols were found to be more toxic than the corresponding alkanamines. A high quality 1-octanol/water partition coefficient (logKow) dependent quantitative structure-activity relationship (QSAR), logIGC−150= 0.78 (logKow)-1.42;r2= 0.934, was developed for alkanamines. This QSAR represented the amine narcosis mechanism of toxic action. No quality QSAR was developed for the aminoalkanols. However, several structure-toxicity features were observed for this class of chemicals. Two-amino-1-hydroxy derivatives being more toxic than the corresponding derivatives, where the amino and hydroxy moieties were separated by methylene groups. Hydrocarbon branching next to the amino moiety resulted in decreased toxicity. Aminoalkanol alters lipid metabolism inT. pyriformis.

ISSN:1062-936X    

DOI:10.1080/10629369808039157

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

Connectivity indices χ of the line graphLand higher line graphsLn,n= 2, 3,…, of the molecular graphGare examined as possible structure-descriptors in QSPR and QSAR studies. In the case of alkanes, regression models based on χ(G), χ(L), χ(L2), χ(L3) and χ(L4) are found to be significantly better than those based solely on the index χ(G), with χ(G) continuing to play an important role. This has been demonstrated for boiling point, molar volume, molar refraction and surface tension. The same model was then applied for predicting the microsomalp-hydroxylation of aniline by alcohols. The QSAR model obtained by using connectivity indices of higher line graphs represents a significant improvement respect to the model using solely χ(G).

ISSN:1062-936X    

DOI:10.1080/10629369808039158

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

The Combined Chemical Dictionary on CD-ROM (Version 1:1, May 1997)

ISSN:1062-936X    

DOI:10.1080/10629369808039159

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

ISSN:1062-936X    

DOI:10.1080/10629369808039160

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

This is a scanned image of the original Editorial Board page(s) for this issue.

ISSN:1062-936X    

DOI:10.1080/10629369808039151

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor