Subject: Summary of Calculation of LogP

From: Arthur Wang <[email-masked]>
Date: Sun, 10 Sep 1995 09:34:18 -0700 (PDT)

Hello, everyone!

Last week I put forward the query for references of calculation of LogP 
and I got a few of very helpful answers. I should thank all who have 
given their kind hands. Here is the summary.

Regards,

Arthur Wang

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|                                                           |
|    Arthur Wang                     Doctoral Candidate     | 
|                                                           |            
|    Molecular Design Lab                                   |
|    Institute of Physical Chemistry, Peking University     |
|    Beijing 100871, P.R.China                              |
|                                                           |
|    E-mail: [email-masked]                          |
|    Tel: 86-10-2501490    Fax: 86-10-2501725               |
|    WWW: http://www.ipc.pku.edu.cn/arthur/homepage.html    |
|                                                           |
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************************SUMMARY OF CALCULATION OF LOGP***********************

Piece One:
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From: [email-masked]

In response to your enquiry: There have been two recent comparisons of 
available methods. 

(i) Viswanadhan et al, J. Comp. Chem. (1993) 14, 1019-1026.

(ii) Moriguchi, I., et al Chem. Pharm. Bull., (1994), 42, 976.

A critique of the second review has also been published.

Leo, A. J., Chem. and Pharm. Bull., (1995), 43, 512.

After the pioneering work of Hansch and Leo on substituent constants for 
'Log P' (or lipophilicity), there have been several atttempts to develop 
methods simpler (such as the use of 'atomic' fragments, pioneered by 
Ghose and Crippen) and more complex (using information from Quantum 
Chemical calculations, such as the BLOGP method developed by N. Bodor and 
associates). Rekker's work on lipophilicity is highly notable as well. 
References for all these works may be found in the two references given 
above. We have developed the 'atomic' method much further, which is as 
yet unpublished. I believe several software companies are also developing 
newer versions & approaches and I am sure you will hear from them.
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Piece Two:
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From: [email-masked] (Jordi Mestres)

	Here you will find enclosed some references on the calculation
of Molecular Lipophilicity Potentials based on the atomic partition of
the total molecular LogP contribution. 
	Sincerely,

	Jordi 

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1	Ghose, A.K. and Crippen, G.M., J. Comput. Chem. 9 (1988) 80.
2	Furet, P., Sele, A. and Cohen, N.C., J. Mol. Graph. 6 (1988) 182.
3	Viswanadhan, V.N., Ghose, A.K., Revankar, G.R. and Robins, R.K., 
	J. Chem. Inf. Comput. Sci. 29 (1989) 163. 
4	Croizet, P., Langlois, M.H., Dubost, J.P., Braquet, P., Audry, E., 
	Dallet, Ph. and Colleter, J.C., J. Mol. Graph. 8 (1990) 153. 
5	Kantola, A., Villar, H.O. and Loew, G.H., J. Comput. Chem. 12 
	(1991) 681.
6	Heiden, W., Moeckel, G. and Brickmann, J. J. Comput.-Aided Mol. 
	Design 7 (1993) 503.
7	Gaillard, P., Carrupt, P.-A., Testa, B. and Boudon, A., 
	J. Comput.-Aided Mol. Design 8 (1994) 83.
8	Rozas, I., Du, Q. and Arteca, G.A., J. Mol. Graph. 13 (1995) 98.
9	Kurochkina, N. and Lee, B., Protein Engineering 8 (1995) 437.
10	Bone, R.G.A. and Villar, H.O., J. Mol. Graph. 13 (1995) 201.
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Piece Three
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From: [email-masked] (Donald Doyle)

This was recently reviewed by Albert J. Leo.  See
Chem. Rev. vol.93, pp1281-1306 (June, 1993).
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Piece Four
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From: "Konrad, IRBM Chemistry, +39-6-91093606" <[email-masked]>

    Below is a list of log P refs which I have in my database.  See chapters
4-5 in reference #13 for a good review of log P calculation methods. I you find
these references useful and best of luck to you in developing your log P
prediction method.

 (1) Dearden, J. C.; Bresnen, G. M. The measurement of partition coefficients.
     Quant. Struct.-Act. Relat.   1988, 7, 133-144.
 (2) Essex, J. W.; Reynodls, C. A.; Richards, W. G. Theoretical determination of
     partition coefficients.  J. Am. Chem. Soc.   1992, 114, 3634-3639.
 (3) Ghose, A. K.; Pritchett, A.; Crippen, G. M. Atomic physicochemical
     parameters for three dimensional structure directed quantitative
     structure-activity relationships III: modelng hydrophobic interactions.  J.
     Comput. Chem.   1988, 9, 80-90.
 (4) Koehler, M. G.; Grigoras, S.; Dunn, W. J., III The relationship between
     chemical structure and the logarithm of the partition coefficient.  Quant.
     Struct.-Act. Relat.   1988, 7, 150-159.
 (5) Moriguchi, I.; Hirono, S.; Liu, Q.; Nakagome, I.; Matsushita, Y. Simple
     method of calculating octano/water partition coefficient.  Chem. Pharm.
     Bull. 1992, 40, 127-130.
 (6) Moriguchi, I.; Hirono, S.; Nakagome, I.; Hirano, H. Comparison of
     reliability of log P values for drugs calculated by several methods.  Chem.
     Pharm. Bull.   1994, 42, 976-978.
 (7) Richards, N. G. J.; Williams, P. B.; Tute, M. S. Empirical methods for
     computing molecular partition coefficients.  I.  Upon the need to model the
     specific hydration of polar groups in fragement-based approaches.  Int. J.
     Quantum Chem.:  Quantum Biology Symposium   1991, 18, 299-316. (8)
 (8) Richards, N. G. J.; Williams, P. B.; Tute, M. S. Empirical methods of
     computing molecular partition coefficients:  II.  Inclusion of
     conformational flexibility within fragment-based approaches.  Int. J.
     Quantum Chem.   1992, 44, 219-233.
 (9) Viswanadhan, V. N.; Reddy, M. R.; Bacquet, R. J.; Erion, M. D. Assessment
     of methods used for predicting lipophilicity:  application to nuceolsides
     and nuceloside bases.  J. Comput. Chem.   1993, 14, 1019-1026.
(10) Bodor, N.; Gabanyi, Z.; Wong, C.-K. A new method for the estimation of
     partition coefficient.  J. Am. Chem. Soc.   1989, 111, 3783-3786.
(11) Bodor, N.; Huang, M.-J. Predicting parition coefficients for isomeric
     diastereoisomers of some tripeptide analogs.  J. Comput. Chem.   1991, 12,
     1182-1186.
(13) Hansch, C.; Leo, A. Exploring QSAR:  Fundamentals and Applications in
     Chemistry and Biology; American Chemical Society: Washington, DC, 1995.
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Piece Five:
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From: [email-masked]

I'll just send some names, probably you have seen the articles:

Leo, Al; Rekker; Ghose & Crippen; Moriguchi; Klopmann; Brinkman--JCICS 
recently; maybe unpublished but the QM people doing solvation test their
model on logP--C. Cramer, Klampt (COSMO program), Tim Clark; I hear that
the Wavefront people have a model; Darvas in a CompuChem module; . . .
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