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Linear Free Energy Relationship (linear + free_energy_relationship)
Selected AbstractsTechnical basis for narcotic chemicals and polycyclic aromatic hydrocarbon criteria.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2000Abstract A method is presented for developing water quality criteria (WQC) for type I narcotic chemicals in general and PAHs in particular. The criteria can be applied to any individual or mixture of narcotic chemicals using only the chemical's octanol-water partition coefficient KOW. It is derived from a database of LC50s comprising 156 chemicals and 33 species, including fish, amphibians, arthropods, mollusks, polychaetes, coelenterates, and protozoans. A target lipid model is proposed that accounts for variations in toxicity due to differing species sensitivities and chemical differences. The model is based on the idea that a target lipid is the site of action in the organism. Further, it is assumed that target lipid has the same lipid-octanol linear free energy relationship for all species. This implies that the slope of the log(LC50),log(KOW) relationship is the same for all species. However, individual species may have varying target lipid body burdens that cause toxicity. The target lipid LC50 body burdens derived from concentration data in the water only are compared to measured total lipid LC50 body burdens for five species. They are essentially equal, indicating that the target lipid concentration is equal to the total extracted lipid concentration. The precise relationship between partitioning in target lipid and octanol is established. The species-specific body burdens are used to determine the WQC final acute value, i.e., the 95-percentile level of protection. An acute-to-chronic ratio is used to compute the body burden corresponding to the WQC final chronic value, which is the procedure used to derive the U.S. Environmental Protection Agency water quality criteria. The criteria are expressed either as dissolved concentrations in the water column or as tissue concentrations. [source] The analysis of solvation in ionic liquids and organic solvents using the Abraham linear free energy relationshipJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 10 2006William E Acree Jr The original article to which this Erratum refers was published in Journal of Chemical Technology and Biotechnology (81: 1441,1446). [source] A data base for partition of volatile organic compounds and drugs from blood/plasma/serum to brain, and an LFER analysis of the dataJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2006Michael H. Abraham Abstract Literature values of the in vivo distribution (BB) of drugs from blood, plasma, or serum to rat brain have been assembled for 207 compounds (233 data points). We find that data on in vivo distribution from blood, plasma, and serum to rat brain can all be combined. Application of our general linear free energy relationship (LFER) to the 207 compounds yields an equation in log BB, with R2,=,0.75 and a standard deviation, SD, of 0.33 log units. An equation for a training set predicts the test set of data with a standard deviation of 0.31 log units. We further find that the invivo data cannot simply be combined with in vitro data on volatile organic and inorganic compounds, because there is a systematic difference between the two sets of data. Use of an indicator variable allows the two sets to be combined, leading to a LFER equation for 302 compounds (328 data points) with R2,=,0.75 and SD,=,0.30 log units. A training equation was then used to predict a test set with SD,=,0.25 log units. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2091,2100, 2006 [source] General linearized biexponential model for QSAR data showing bilinear-type distributionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2005Peter Buchwald Abstract A major impediment of many QSAR-type analyses is that the data show a maximum or minimum and can no longer be adequately described by linear functions that provide unrivaled simplicity and usually give good description over more restricted ranges. Here, a general linearized biexponential (LinBiExp) model is proposed that can adequately describe data showing bilinear-type distribution as a function of not just often-employed lipophilicity descriptors (e.g., log P) but as a function of any descriptor (e.g., molecular volume). Contrary to Hansch-type parabolic models, LinBiExp allows the natural extension of linear models and fitting of asymmetrical data. It is also more general and intuitive than Kubinyi's model as it has a more natural functional form. It was obtained by a differential equation-based approach starting from very general assumptions that cover both static equilibriums and first-order kinetic processes and that involve abstract processes through which the concentration of the compound of interest in an assumed "effect" compartment is connected to its "external" concentration. Physicochemical aspects placing LinBiExp within the framework of linear free energy relationship (LFER) approaches are presented together with illustrative applications in various fields such as toxicity, antimicrobial activity, anticholinergic activity, and glucocorticoid receptor binding. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2355-2379, 2005 [source] Mechanistic Investigation of the Dipolar [2+2] Cycloaddition,Cycloreversion Reaction between 4-(N,N -Dimethylamino)phenylacetylene and Arylated 1,1-Dicyanovinyl Derivatives To Form Intramolecular Charge-Transfer ChromophoresCHEMISTRY - A EUROPEAN JOURNAL, Issue 1 2010Yi-Lin Wu Abstract The kinetics and mechanism of the formal [2+2] cycloaddition,cycloreversion reaction between 4-(N,N -dimethylamino)phenylacetylene (1) and para -substituted benzylidenemalononitriles 2,b,2,l to form 2-donor-substituted 1,1-dicyanobuta-1,3-dienes 3,b,3,l via the postulated dicyanocyclobutene intermediates 4,b,4,l have been studied experimentally by the method of initial rates and computationally at the unrestricted B3LYP/6-31G(d) level. The transformations were found to follow bimolecular, second-order kinetics, with =13,18,kcal,mol,1, ,,30,cal,K,1,mol,1, and =22,27,kcal,mol,1. These experimental activation parameters for the rate-determining cycloaddition step are close to the computational values. The rate constants show a good linear free energy relationship (,=2.0) with the electronic character of the para -substituents on the benzylidene moiety in dimethylformamide (DMF), which is indicative of a dipolar mechanism. Analysis of the computed structures and their corresponding solvation energies in acetonitrile suggests that the rate-determining attack of the nucleophilic, terminal alkyne carbon onto the dicyanovinyl electrophile generates a transient zwitterion intermediate with the negative charge developing as a stabilized malononitrile carbanion. The computational analysis predicted that the cycloreversion of the postulated dicyanocyclobutene intermediate would become rate-determining for 1,1-dicyanoethene (2,m) as the electrophile. The dicyanocyclobutene 4,m could indeed be isolated as the key intermediate from the reaction between alkyne 1 and 2,m and characterized by X-ray analysis. Facile first-order cycloreversion occurred upon further heating, yielding as the sole product the 1,1-dicyanobuta-1,3-diene 3,m. [source] | ||||||||||