Additivity fragment constants

The obvious drawback of this method is that the parent solute, at least, has to be available or must be synthesized, and its log P value has to be determined experimentally. Nys and Rekker therefore developed a method known as the fragmental constant approach, which is based on the additivity of fragment contributions to the molecular lipophilidty [7] (see Eq. (9), where a( is the inddence of fragment i, fi the lipophilic fragment constant, Ci a corredion factor, and the frequency of Cm). 

The correction term in Eq. (9) shows that the basic assumption of additivity of the fragmental constants obviously does not hold true here. Correction has to be appHed, e.g., for structural features such as resonance interactions, condensation in aromatics or even hydrogen atoms bound to electronegative groups. Astonishingly, the correction applied for each feature is always a multiple of the constant Cu, which is therefore often called the magic constant . For example, the correction for a resonance interaction is +2 Cj, or per triple bond it is -1 A detailed treatment of the Ef system approach is given by Mannhold and Rekker [5]. 

Various methods for estimating transfer constants in radical polymerization have been devised. The methods are applicable irrespective of whether the mechanism involves homolytic substitution or addition-fragmentation. 

This equation can be solved numerically to give values of Clr and Ctr.404 For reversible addition-fragmentation chain transfer (RAFT) (Scheme 6.5), the rate constant for the reverse reaction is defined as shown in eq. 22 ... 

Compounds with a thiocarbonyl a to the S-S bond such as the dithiuram (e.g. 8f2Al and xanthogen disulfides (e.g. 9)M have transfer constants that are much higher than other disulfides. In part, this may be due to the availability of another mechanism for induced decomposition (Scheme 6.9) involving addition to the C S double bond and subsequent fragmentation. Thiocarbonyl double bonds are very reactive towards addition and an addition-fragmentation mechanism has been demonstrated for related compounds (Section 6.2.3.5). 

Most monosulfides generally have very low transfer constants. Exceptions to this rule are allyl sulfides (Section 6,2.3.2) and thiocarbonylthio compounds such as the trithiocarbonatcs and dithiocstcrs (Section 9.5.3) that react by an addition-fragmentation mechanism. 

In the case of allyl peroxides (12 X= CH2, A=CH2, BO),1 1 1 intramolecular homolytic substitution on the 0-0 bond gives an epoxy end group as shown in Scheme 6.18 (1,3-Sn/ mechanism). The peroxides 52-59 are thermally stable under the conditions used to determine their chain transfer activity (Table 6.10). The transfer constants are more than two orders of magnitude higher than those for dialkyi peroxides such as di-f-butyl peroxide (Q=0.00023-0.0013) or di-isopropyl peroxide (C =0.0003) which are believed to give chain transfer by direct attack on the 0-0 bond.49 This is circumstantial evidence in favor of the addition-fragmentation mechanism. 

For addition-fragmentation chain transfer, the rate constants for the forward and reverse reaclions are defined as shown in eqs. 21 and 22 respectively. 

An intramolecular mechanism of the rearrangement has been shown in the special ESR study (refs. 21, 22), conducted on the model radicals, generated by abstraction of a bromine atom from T2 " the rate constant K2, equal to (5.0 + 0.3) X 104 sec- at 22°C, has been also determined. In addition, fragmentation of radical... 

Lipophilicity in particular, as reflected in partition coefficients between aqueous and non-aqueous media most commonly water (or aqueous buffer) and Z-octanol,has received much attention [105,141,152,153,176,199,232,233]. Logic )W for the octanol-water system has been shown to be approximately additive and constitutive, and hence, schemes for its a priori calculation from molecular structure have been devised using either substituent tt values or substructural fragment constants [289, 299]. The approximate nature of any partition coefficient has been frequently emphasized and, indeed, some of the structural features that cause unreliability have been identified and accommodated. Other complications such as steric effects, conformational effects, and substitution at the active positions of hetero-aromatic rings have been observed but cannot as yet be accounted for completely and systematically. Theoretical statistical and topological methods to approach some of these problems have been reported [116-119,175,289,300]. The observations of linear relationships among partition coefficients between water and various organic solvents have been extended and qualified to include other dose-response relationships [120-122,160,161,299-302]. 

Cramer actually developed two schemes for applying the BC(DEF) values a hierarchical additive-constitutive one and a linear additive-constitutive one. The two schemes are equivalent, but the latter is easier for hand calculations, and thus is the only one presented here. Table 2.6 provides the BC(DEF) fragment constants from the linear model. 

Commonly used methods are based on fragment constants. The fragmental approaches are based on a simple addition of the lipophilicity of the individual molecular fragments of a given molecule. Three commercially... 

This technique for controlling radical polymerizations is based on one of the oldest technique, that of chain transfer, and has often been used in telomeriza-tion [83]. Similar to the concept of degenerative transfer with alkyl iodides [50, 51, 84], reversible addition fragmentation chain transfer with dithio esters (RAFT) [52-55, 85] is successful because the rate constant of chain transfer is faster than the rate constant of propagation. Analogous to both nitroxide-medi-... 

Solute descriptors are available for about 4,000 compounds, with some large compilations reported [42,43,49,58,68]. For additional compounds estimation methods are available using fragment constants [46,50,63-65]. An early version of a software program to estimate solute descriptors from structure has appeared [71]. In all other cases it is possible to calculate Vx and R2 and determine the other descriptors from experimental distribution constants and chromatographic measurements. If data is available for a particular solute in three systems with significantly different system constants then 2, , SP2 can be determined as the solution to three simultaneous... 

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