Fragmentation coefficients

In the following, the atom/fragment contribution method (AFC method) developed by Meylan and Howard (1995) is used to illustrate the approach. This method is similar to the CLOGP method, but it is easier to see its application without using a computer program. Here, we confine ourselves to a few selected examples of fragment coefficients and correction factors. This will reveal how the method is... 

Table 7.4 Selected Atom/Fragment Coefficients,/k for log Ki0VJ Estimation at 25°C (Eqs. 7-15 and 7-16)a...

Estimate the Kiow values at 25°C of (a) ethylacetate, (b) 2,3,7,8-tetrachloro-dibenzodioxin, (c) the herbicide 2-s-butyl-4,6-dinitrophenol (Dinoseb), (d) the insecticide parathion, and (e) the hormone testosterone using solely the fragment coefficients and correction factors given in Tables 7.4 and 7.5 (Eq. 7-15). 

Table 17-2 Examples of Fragment Coefficients (Eq. 17-23) Indicating How a Given Structural Moiety Influences the Aerobic Biodegradability of a Compound (from Tunkel et al., 2000).

The SRC program KOWWIN uses an atom/fragment contribution method to predict log Kow. This is a reductionist method (the fragment coefficients were derived by multiple regression from a development set of reliably measured log Kow values). The other main software tool, ClogP for Windows (Leo, 1993) is a constructionist method (the fragment coefficients are evaluated from the simplest examples in which they occur). Both methods have a high level of accuracy and are widely accepted as the best tools available. 

Table 3.7.1 Fragmentation coefficients of YbBr2 and YbBr molecules...

A two-site immunometric assay of undecapeptide substance P (SP) has been developed. This assay is based on the use of two different antibodies specifically directed against the N- and C-terminal parts of the peptide (95). Affinity-purified polyclonal antibodies raised against the six amino-terminal residues of the molecule were used as capture antibodies. A monoclonal antibody directed against the carboxy terminal part of substance P (SP), covalently coupled to the enzyme acetylcholinesterase, was used as the tracer antibody. The assay is very sensitive, having a detection limit close to 3 pg/mL. The assay is fiiUy specific for SP because cross-reactivity coefficients between 0.01% were observed with other tachykinins, SP derivatives, and SP fragments. The assay can be used to measure the SP content of rat brain extracts. 

Octano/—Water Partition Coefficient. The Fragment approach (234—236) has been reviewed (227) and another method similar to the UNIFAC refit for Henry s constant has been proposed. Improved accuracy for many species and the abiUty to correct for temperature effects have been claimed for the newer method. 

The similarity matrices are constructed by one in-house program developed inside CHIRBASE using the application development kit of ISIS. They contain the similarity coefficients as expressed by the Tanimoto method. In ISIS, the Tanimoto coefficients are calculated from a set of binary descriptors or molecular keys coding the structural fragments of the molecules. 

If both addition and fragmentation arc irreversible the kinetics differ little from conventional chain transfer. In the more general case, the rate constant for chain transfer is defined in terms of the rate constant for addition and a partition coefficient which defines how the adduct is partitioned between products and starting materials (eq. 19). 

Phenomenological evidence for the participation of ionic precursors in radiolytic product formation and the applicability of mass spectral information on fragmentation patterns and ion-molecule reactions to radiolysis conditions are reviewed. Specific application of the methods in the ethylene system indicates the formation of the primary ions, C2H4+, C2i/3+, and C2H2+, with yields of ca. 1.5, 1.0, and 0.8 ions/100 e.v., respectively. The primary ions form intermediate collision complexes with ethylene. Intermediates [C4iZ8 + ] and [CJH7 + ] are stable (<dissociation rate constants <107 sec.-1) and form C6 intermediates which dissociate rate constants <109 sec. l). The transmission coefficient for the third-order ion-molecule reactions appears to be less than 0.02, and such inefficient steps are held responsible for the absence of ionic polymerization. 

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