Quantitative cationic activity relationships

Walker JD, Enache M, Dearden JC. Quantitative cationic-activity relationships for predicting toxicity of metals. Environ Toxicol Chem 2003 22 1916-35. 

Developing and validating Quantitative Cationic Activity Relationships or (Q)CARs to predict the toxicity [of] metals is challenging because of issues associated with metal speciation, complexation and interactions within biological systems and the media used to study these interactions. 

QICARs use the metal-Iigand bonding characteristics to predict metal ion toxicity (Newman et al., 1998). In general, the models developed for metals with the same valence were better than those combining mono-, di-, and trivalent metals. The metal ion characteristics included a softness parameter and the absolute value of the log of the first hydrolysis constant. The first stable reduced state also contributed to several two-variable models. Since most metals can interact in biological systems as cations and because toxicity of metals depends on cationic activity, the term (quantitative) cationic-activity relationships or (Q)CARs also describes the qualitative and quantitative relationships for predicting the bioconcentration, biosorption, or toxicity of metals, from their physicochemical properties and natural occurrence levels. 

Source Appeared in J.D. Walker, M. Enache, and J.C. Dearden. Quantitative Cationic Activity Relationships for Predicting Toxicity of Metals. Environ. Toxicol. Chem. 22 (2003) 1916-1935, T-3. 

In this respect, Quantitative Ion Character-Activity Relationships (QICARs) and Quantitative Cationic-Activity Relationships (QCARs) have recently been developed (Ownby and Newman 2003, Walker et al. 2003). More research efforts are needed in this field, however, in order to develop and validate appropriate models. 

An instructive quantitative structure-activity relationship (QSAR) analysis carried out on published data about a large set of cationic lipids, including both successful and unsuccessful compounds, permitted to delineation of a high-efficiency region... 

Furthermore, for some cationic surfactants, quantitative structure-activity relationships have been established for daphnids and fish. Increments used in the ECOSAR toxicity estimation software (Syracuse Research Center, freely available from the US Environmental Protection Agency as part of the software EPI Suite) are -0.13 and -0.37 for each carbon atom in monoalkyl quaternary ammonium surfactants in daphnids and fish, respectively. These increments are much smaller than the ones found here. Our increments for the n-alkyl chain in Rj position are more in accordance with increments for CH2 groups in n-octanol/water partitioning constant estimation procedures, which are, e.g., 0.66 and 0.49 in Hansch and Leo s method and Meylan and Howard s method, respectively [20]. This suggests that uptake into the cells is governed by lipophilicity, or maybe more exactly by membrane/water partitioning [21, 22]. 

This chapter discusses quantitative structure-activity relationships (QSARs) for predicting cation toxicity, bioconcentration, biosorption, and binding strength. Several approaches were used to identify these QSARs. First, the test systems, test substances, QSARs, and statistical analyses of each QSAR were extracted from the references cited by Walker et al. (2003). These efforts produced 21 references associated with 97 QSARs for predicting cation toxicities (Table 5.1). These QSARs are discussed in more detail in chapter Sections 5.2,5.3, and 5.5. 

Arning, J., Stolte, S., Boschen, A., Stock, R, Pimer, W.R., Welz-Biermann, U, Jastorff, B. and Ranke, J., Qualitative and quantitative structure activity relationships for the inhibitory effects of cationic head groups, functionalised side chains and anions of ionic liquids on acetylcholinesterase. Green Chem. 10, 47-58 (2008). 

In this work the relationships were interpreted in terms of the PMO theory. From the interpretation it follows that the linear relationship must hold between the free activation energy of the rearrangement and the length of the double carbon-carbon (C = C) bond of the compounds formed as the rrault of the methyl cation departure from the respective carbonium ions. Indeed, such a relationship has been found Correlations according to Eq. (4)-(6) were successfuUy used to quantitatively describe the isomerization of methylbenzenes and methylnaphthalenes in... 

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