title: Correlation weighting of valence shells in QSAR analysis of toxicity.
abstract: In the rainbow trout (Oncorhynchus mykiss), we studied the acute toxicity LC(50)-96 h of 274 organic pesticides with a wide variety of molecular structures. Optimization of correlation weights of local and global graph invariants (OCWLGI) gave quantitative structure-activity relationships (QSARs) for predicting toxicity. We used a labeled hydrogen-filled graph (LHFG) to elucidate the molecular structure. We also used the extended connectivity of zero ((0)EC(k)), first ((1)EC(k)), and second ((2)EC(k)) order, numbers of path lengths 2 (P2(k)) and 3 (P3(k)) starting from a given vertex in the LHFG, and valence shells of second order (S2(k)). S2(k) is the sum of the degree of vertices at distance 2 from a given vertex k. The presence of three-, five-, and six-member cycles and hydrogen bond indices suggested they might be used as global LHFG invariants. We applied this method to a broad set of pesticides, to predict toxicity for the trout. The best model used weighted S2(k) and global LHFG invariants. Statistical characteristics of this model are as follows: n=233, r(2)=0.7689, r(2)(pred)=0.7688, s=0.75, F=769 (training set); n=41, r(2)=0.6421, r(2)(pred)=0.4241, s=1.14, F=70 (test set).
authors.affiliation: Laboratory of Environmental Chemistry and Toxicology, Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, 20157 Milan, Italy. aatoropov@yahoo.com
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Toropov
authors.forename: Emilio
authors.initials: E
authors.lastname: Benfenati
mesh_terms: D000818:Animals; D008956:Models, Chemical; D015394:Molecular Structure; D017686:Oncorhynchus mykiss; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D010575:Pesticides