LOGP program

Other kinds of tautomerism are not so obvious, and the ability of the ACD / LogP program to call attention to them may make it quite valuable. Camptothecin, as Figure 5.8 shows, provides such an example. 

A certain variability of this parameter is likely both in the measured values and the calculated values. Typically programs to calculate log/ consider the presence of atoms and fragments of the molecules. Thus the predictive models based on log/, even if they are apparently based on a single parameter, rely on many more parameters, statistically identified within the different programs to calculate log/. There are several logP programs that are commer-... 

The chromatographic parameters were compared with calculated H2O-u-octanol logP value (2.23) (by CLOGP program) (96JC(A)135). 

The final log P model was obtained by correlahng a total of 94 parameters with the logP values through MLR analysis. Correchon fragments idenhfied by the CASE program can be classified into four categories (i) tautomerization effects,... 

The function Data EqAH2, m simulates the pH-titration of a weak diprotic acid, AH2, in acid excess, with a strong base. The computation of the equilibria is similar to the examples Eql. m and Eq2. m given in the Chapters Example General 3-Component Titration (p.56) and Example pH Titration of Acetic Acid (p.58). From the present point of view, the important aspect is that all variables are collected in one structure s. The model is now stored in s.Model, the logP values in s. log beta, etc. Importantly, all the information contained in s is returned to the invoking programs. 

The measurement of the solubility of drugs in polar and non-polar media is very important in the pharmaceutical field. One method proposed to describe this solubility is the partition coefficient between octanol and water. The mathematical calculation of an octanol-water partition coefficient from values for functional groups was first proposed by Hansch et al. as Hansch s n constants,1 and was later developed by Rekker as hydrophobic fragmental constants (logP).2 This method was further improved by the use of molecular connectivities.17 The prediction of logP values can be performed by either a computer program or by manual calculation. For example, approximate partition coefficients (log P) have been calculated by Rekker s method ... 

So many calculation methods have been published in the last five years that it is not possible to examine them all in detail in this chapter, which does discuss the strengths and weaknesses of the various approaches. For convenience and reproducibility, most users require computerized calculation, and so this chapter emphasizes these methods. Man-nhold (1996) recently published a comparative study and van de Waterbeemed (1996) published a list of addresses for the programs. More information is available on the World Wide Web (http / / www.pharma.ethz.ch/qsar/logp.html). 

Of the many listed by Mannhold, three programs, differing significantly in methodology, were chosen for comparison of performance KOWWIN, ACD/LogP, and CLOGP. As Table... 

For users who prefer to draw in new structures, the later versions of Chem Draw will deliver a SMILES notation which can be used via cut and paste commands, and ISIS Draw delivers a MOLfile which can be automatically converted to a SMILES file. ACD / LogP uses a proprietary drawing program, MolDraw, which is easy to learn and use. Entry by name in ACD is accomplished via a Dictionary with about 48,000 entries. Drawn structures can be saved to a file, but in version beta 0.9 of ACD/LogP there is no method of batch entry from either SMILES files or MDL MOLfiles. 

The bottom line is that a prospective user should spend sufficient time with an adequate demonstration version of any computerized log P calculator, including the many not directly mentioned in this chapter, to make sure it will perform to meet his/her specific needs. Perhaps the best way a prospect can shop for vendors supplying such programs is through the contacts van de Waterbeemd lists (1996) or http / /www.pharma.ethz.ch/ qsar/logp.html. 

However, when using the ACD program for calculating partition coefficients, a octanol water logP value of 3.59 0.41 was calculated. Using the ACD program that calculated the pH distribution of distribution coefficients, the data plotted in Figure 2 were obtained. 

Computational chemistry programs can calculate a range of molecular parameters with varying accuracy. Some properties such as LogP are appropriate to calculate only for the molecules being tested while other parameters such as molecular weight may be useful for the component reagents. 

SlogP Program for the estimation of logP using the atom - weighted solvent accessible surface areas... 

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