version date: 1 December 2006 the methyl group is reported log PCH3=log P-log P The following"by fragments "methods was supported by Rekker and Mannhold, who stated that log P can be calculated as the sum of the fragment values plus certain correction factors. They determined the averaged contributions of simple fragments, using a large database of experimentally measured log P values [17, 18]. Rekker did not indicate which fragment could be considered a valid fragment. The log P of molecules can be calculated using the formula log p=>ann+>bmFm where a is the number of occurrences of fragment f of type n while b is the number of occurrences of correction factor F of type m The well-known CLOGP method clearly represents an improvement of the Rekker approach and in fact, can be expressed by the same equation. CLOGP program breaks molecules into fragments and sums these constant fragment values and structure-dependent correction values taken from Hansch and Leo's database, to predict log P of several organic molecules. The program divides the target molecule into different fragments following a set of simple rules not alterable by users CLOGP represents the first stand-alone program developed by Pomona MedChem, following Rekker general formulation. The program is now available on the Web (http://www.daylightcom/daycgi/clogp) Different from chemical group fragments, the methods based on atomic contribution and/or surface area use atomic fragments and surface area data to predict hydrophobicity. The contribution of each atom to a molecule, in terms of hydrophobicity, can be evaluated by multiplying the corresponding atomic parameter by the degree of exposure to the surrounding solvent. The exposure degree is typically represented by the solvent-accessible surface area(SASA). The first promoters of this method were Broto and his colleagues, who developed a 222 descriptors set, made by combinations of up to four atoms with specific bonding pathways up to four in length, reaching a precision of about 0.4 log units [19]. Later, the concept of sAsa was used by Iwase [20] and Dunn [21] in principal component analysis, to improve their log P estimations. Dunn computed the isotropic surface area, calculating the number of water molecules able to hydrate the polar portions of the solute molecules. As an example, one water molecule was allowed for groups as nitro, aniline, ketones, and tertiary amines, while two waters are allowed for other amines, three for arboxyls, and five for amide groups. The use of SASA parameters has been extended and introduced in several log P calculation algorithms, like the program HINT created by abraham and Kellogg in 1991, which will be subsequently discussed and used for a practical session Various researchers diglot. apree orgpu BreXioHs yareegrteda tragmestl methods, claiming that a4 the methyl group is reported. log P CH3 = log P – log P The following “by fragments” methods was supported by Rekker and Mannhold, who stated that log P can be calculated as the sum of the fragment values plus certain correction factors. They determined the averaged contributions of simple fragments, using a large database of experimentally measured log P values [17,18]. Rekker did not indicate which fragment could be considered a valid fragment. The log P of molecules can be calculated using the formula log P = ∑anfn + ∑bmFm where a is the number of occurrences of fragment f of type n while b is the number of occurrences of correction factor F of type m. The well-known CLOGP method clearly represents an improvement of the Rekker approach and, in fact, can be expressed by the same equation. CLOGP program breaks molecules into fragments and sums these constant fragment values and structure-dependent correction values taken from Hansch and Leo’s database, to predict log P of several organic molecules. The program divides the target molecule into different fragments following a set of simple rules not alterable by users. CLOGP represents the first stand-alone program developed by Pomona MedChem, following Rekker general formulation. The program is now available on the Web (http://www.daylight.com/daycgi/clogp). Different from chemical group fragments, the methods based on atomic contribution and/or surface area use atomic fragments and surface area data to predict hydrophobicity. The contribution of each atom to a molecule, in terms of hydrophobicity, can be evaluated by multiplying the corresponding atomic parameter by the degree of exposure to the surrounding solvent. The exposure degree is typically represented by the solvent-accessible surface area (SASA). The first promoters of this method were Broto and his colleagues, who developed a 222 descriptors set, made by combinations of up to four atoms with specific bonding pathways up to four in length, reaching a precision of about 0.4 log units [19]. Later, the concept of SASA was used by Iwase [20] and Dunn [21] in principal component analysis, to improve their log P estimations. Dunn computed the isotropic surface area, calculating the number of water molecules able to hydrate the polar portions of the solute molecules. As an example, one water molecule was allowed for groups as nitro, aniline, ketones, and tertiary amines, while two waters are allowed for other amines, three for carboxyls, and five for amide groups. The use of SASA parameters has been extended and introduced in several log P calculation algorithms, like the program HINT created by Abraham and Kellogg in 1991, which will be subsequently discussed and used for a practical session. Various researchers did not agree with previously reported fragmental methods, claiming that a CH3 <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006