Subject: LogP estimation questions

From: [email-masked] (Joe M Leonard)
Date: Wed, 16 Nov 1994 18:30:38 -0500

Folks,

	Kantola, Villar and Loew discuss an atom-based method for 
estimating Log P for molecules containing H, C, N, O, F and Cl.  The
specific reference is "Atom Based Parameterization for a Conformationally
Dependent Hydrophobic Index", A. Kantols, H. O. Villar and G. H. Loew,
J. Comp. Chem. 12, 681(1991).  I have several questions about this work,
and I hope somebody familiar with it is reading...

1) It refers to Van der Waals radii from Gavezzotti, J. Am. Chem. Soc.
105, 5220(1983).  Does anybody have these numbers on-line or at hand to
post or email them?  The article implies that there are differences with
these values as compared with "typical" values, and I am curious (havving
spent some time collecting VdW radii).

2) Has there been any corrections to this work?  If I compare my results
against those published in the article, the results for F-containing
compounds seem VERY different.

3) Has this work been extended to additional atoms?  A later review
article (Viswanadhan et al, J. Comp. Chem. 14, 1019(1993)) does not
refer to this work.

4) This work refers to the total charge of individual atoms.  In order
to reproduce the published results, I have to substitute the valence
charge (particularly for Cl).  This discrepancy, coupled with the
fact that MNDO and AM1 are being used, suggests the valence charge was used
without explicit reference.  Is this correct?

I would appreciate any comments from folks interested in log-P estimation,
particularly in regards to non-database methods (atom or fragment QSAR
models, etc).

Thanks in advance,

Joe Leonard
[email-masked]

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From: Stefan Unger <[email-masked]>
Date: Wed, 16 Nov 1994 19:06:25 -0800 (PST)

> particularly in regards to non-database methods (atom or fragment QSAR

If you mean by "atom or fragment QSAR" that you dont want additive 
substituent models (like CLOGP from Hansch and Leo, or Rekker's method), 
then there is a commercially available package (which 
I happen to sell...) called SciLogP (and also SciLogW for solubility 
estimation) which is an implimentation of Bodor's method.  This uses
an open regression model, based on a database, but is not "additive" in 
the same sense as the CLOGP method.
Another old-by-now "computational" method was by Hopfinger, for example. 
And, HyperChem (which I also sell...) has Crippen and Ghose method. I hope 
this helps.