Estimation methods fragment contribution method

Meylan, W. M., Howard, P. H. Atom/ fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sd. 1995, 84,... 

Estimation from molecular connectivity index/fragment contribution method (Meylan et al. 1992, Lohninger 1994) ... 

The Atom/Fragment Contribution Method for Estimation of the Octanol-Water Partition Constant... 

Illustrative Example 7.2 Estimating Octanol-Water Partition Constants from Structure Using the Atom/Fragment Contribution Method Illustrative Example 7.3 Estimating Octanol-Water Partition Constants Based on Experimental KI0W s of Structurally Related Compounds... 

Estimating Octanol-Water Partition Constants from Structure Using the Atom/Fragment Contribution Method... 

What are the major difficulties of any atom/fragment contribution method for estimation of solvent-water partition constants from structure ... 

Meylan, W.M., and P.H. Howard. 1995. Atom/Fragment Contribution Method for Estimating Oc-tanol-Water Partition Coefficients. ]. Pharm. Sci, 84, 83-92. 

The method was tested on a validation set consisting of 205 compounds (41 nonpolar and 164 polar chemicals). In addition, the method was compared to regression methods using S and Kow as the input variables. Results show that this model outperforms and covers a wider range of chemical structures than models based on Kow aqueous solubility, or single MCIs. Meylan et al. (1992) concluded that the MCI-fragment contribution method was clearly superior in the prediction of K(k , although in many cases experimental values of S and Kow were not available and estimated values were used. They presented no direct comparison with other MCI-based estimation methods. 

Meylan, W.M., Howard, P.H. and Boethling, R.S. (1992). Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients. Environ.Sci. Technol.,26,1560-1567. Meylan, W.M. and Howard, P.H. (1995). Atom/Fragment Contribution Method for Estimating Octanol-Water Partition Coefficients. J.Pharm.Sct, 84, 83-92. 

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. 

Most methods used by medicinal chemists to estimate the partition properties of a compound are so-called fragment contribution methods. The basic idea behind all these methods is quite similar. Molecules are broken down into predefined fragments and their corresponding contributions are summed up to obtain the final log P value based on the following equation ... 

The group contribution method Stein and Brown (1994) developed is the most robust group contribution method that can be applied in a straightforward manner i.e., it can cover a broader variety of chemicals than the Simamora and Yalkowsky and Cramer methods (described above) and is relatively easy to use compared to the method of Lai et al. (1987) (described below). The work is an extension of the work by Jobak and Reid (1987). The extension is primarily an increase in the number of fragment constants, from 41 to 85. However, many of the new groups are simply subdivisions of those Jobak and Reid used. The method assumes no interaction between fragments. A computerized version of the estimation method, called MPBPVP, is available from Syracuse Research Corporation (Syracuse, NY). 

Meylan, W., Howard, PH. (1991) Bond contribution method for estimating Henry s law constants. Environ. Toxicol. Chem. 10,1283-1293. Meylan, W., Howard, P.H., Boethling, R.S. (1992) Molecular topology/fragment contribution method for predicting soil sorption coefficient. Environ. Sci. Technol. 26(8), 1560-1567. 

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