Atom-based methods

Atom-based methods [40, 57-68] cut molecules down to single atoms and commonly do not apply correction rules. According to Eq. (9) they work by summing the products of the contribution of an atom type i times the frequency of its presence in a query molecule  

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In this chapter, we describe substructure-based logP calculation approaches comprising fragmental and atom-based methods property-based approaches are discussed in Chapter 15. 

I 14 Prediction of Log with Substructure-based Methods Tab. 14.3 Atom-based methods. 

XLOGP [67, 68] is a further atom-additive method, as expressed by its almost exclusive use of atomic contributions. However, in contrast to pure atom-based methods correction rules are defined, to account for intramolecular interactions, which is typical for fragmental methods. 

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). 

Separating methods which use molecular parts into two categories, atom-based or fragment-based/ seems to make a distinction without a significant difference. In atom-based methods, each atom of the molecule is examined in respect to its connectivity index, and to the oxidation and hybridization state of all those atoms directly attached to it (Viswa-nadhan, 1989) or to some similar measure of atomic state (Broto, 1984). 

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. 

With the widespread application of lipophi-licity and partitioning to biophysical processes, a wide variety of tools is currently available to estimate partition coefficient. Several recent reviews of programs and methods that are commercially available have been published (25-28). Predictive methods may be broken down into the following basic approaches to partition coefficient estimation (i) group contribution methods, by use of molecular fragments (2) group contribution, by use of atom-based contributions (5) conformation-dependent or molecular methods (4) combined fragment and atom-based methods and (5)other physicochemical methods. 

As an illustration of the first point, atom-based methods sometimes attempt to limit the number of possibilities to be searched by assuming only sp connections. Fragment buildup procedures can also lose diversity depending on how the fragments are permitted to join together (e.g., in the construction of... 

Even with the enhancements described above for atom based methods, when the molecules being studied are structurally unrelated, the utility of atom correspondences inevitably diminishes. In addition, it is difficult to seek out structurally diverse classes of compounds using atomic correspondences. Alternative methods that utilize molecular fields, volumes, or surfaces have been developed. The most widely used metric of molecular similarity is that of Carbo. ... 

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