Lipophilicity atom-based

Atom-based Methods As for fragmental methods, the molecule is considered as composed of fragments, but these latter are single atoms instead of functional groups. Each atom is characterized by its own lipophilicity constant and the global lipophilicity is then a sum of each contribution (Equation 5.4). 

A lipophilicity model based on atomic charges, surface areas, dipole moments, and a set of adjustable parameters depending only on the atomic number [Kantola et al., 1991]. The parameter values are determined in order to reproduce experimental logP values using the following general model ... 

The second set of descriptors describes hydrophobic surface properties of a molecule. As with the first set, the second set contains similar partial hydrophobic and partial hydrophilic surface area descriptors (PPHS-%and PNHS-%, respectively), differences in partial surface area descriptors (FPHS-% and FNHS-%), as well as total surface area weighted descriptors (WPHS-x and WNHS-%). In addition, two descriptors assessing the most hydrophobic atom and the most hydrophilic atom on the overall lipophilicity are also described (RPH and RNH). The atom-based fractional log P contributions used for calculations are those of Wildman and Crippen [37] and... 

More recently, computer methods have been devised to calculate these values. The molecule is broken down into fragments of known lipophilicity, and the logP is calculated using various computer routines. Alternatively, there are atom-based methods, and lipophilicity is measured, and calculated log Ps (c log Ps) agreement is reasonably good. 

Most of the methods that are used to predict logP values of molecules depend on fragmental codes or lipophilicity increments based on extended atom types. Obviously, it is possible to assign lipophilicity increments directly to every atom of a structure as an atomic property. The distribution of lipophilic and hydrophilic properties in a molecule can be described in this way [53]. 

Atom-based lipophilicity contributions and molar refractivity contributions have been derived for 3D QSAR studies [266 — 269]. Audry et ai defined molecular lipophilicity potentials [914—916] for the determination of lipophilic and hydrophilic regions of a molecule. 

The CLIP approach was developed by the group of Testa [55]. It is based on the atomic lipophilic system of Broto and Moreau [56] and uses a modified exponential distance function of which differs from the e function of Fauchere et al. [45]. In addition the authors restricted the distance function at 4A to avoid influence of too distant elements. The most recent version of CLIP uses a Fermi-like distance function, which does not need any cutoff values [57]. Another implementation of the approach is available in the VEGA software provided by Pedretti et al. [58]. 

A method with LOQ at ppt levels was developed based on LLE followed by GC-AFID for the determination of trace concentrations of nitrobenzene, l-chloro-2-nitrobenzene and synthetic fragrances such as musk xylene (223) and musk ketone (224). The method was applied to study the distribution of these compounds in environmental samples of North Sea waters460. GC with atomic emission detection (AED) has been successfully applied to the determination of nitro musks in human adipose tissues, at ppb concentration levels. A clean-up procedure for nonpolar substances and element-specific detection with AED enabled for the first time target screening analysis for lipophilic nitro aromatic compounds. The lack of sensitivity of AED was compensated by higher concentrations of the extracts... 

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