Subject: Ghose-Crippen LogP estimation questions

From: "Joe Leonard" <[email-masked]>
Date: Thu, 19 Jan 1995 10:01:02 -0800

Folks,

	I have been working with the Ghose-Crippen LogP estimation method (J.
Comp. Chem. 9,80(1990)), and have several questions regarding the atom-typing
rules described in the paper(s):

1. They refer to a program called CLASIF as being able to take structural
information and generate the atom type.  Obviously, having this program would
"answer" all questions - is it available anywhere?

2. They make a distinction between "groups linked through carbon" (R-) and
aliphatic groups (Al-).  In this model, do aliphatic groups only contain carbon
and hydrogen atoms, or can they contain any atom as long as they are
singly-bound.  Also, can H- match Al-?

3. They discuss aromatic groups - as with (2) are these carbon/hydrogen
aromatics only, or can they contain heteroatoms?

4. Their Type 51 is called "H bound to alpha-C" - is this the alpha carbon of
peptides or is it something else?

5. How are "formal oxidation numbers" handled for aromatic systems.  The model
refers to carbons with integer oxidation numbers.  Since aromatic systems could
have non-integer oxidation numbers (1.5, etc), should they be rounded up or
down?  In general, how are such systems handled?

6. Does Type 57 (phenol, enol, carboxyl OH) include Csp-OH oxygens?

7. Is Type 72 amide nitrogens RC(=O)-N or is RCO-N something like
   R-C-O-N compounds?

8. Is Type 76 R(=O)-NO2 or R-O-NO2?  Looking at the other groups in Type 76, it
seems like the former is correct...

9. The model does not include cationic nitrogens - has this been dealt with in
a later paper?  Are there later papers?

10. Type 78 is Ar-N=X and X-N=X - what about Al-N=X?

11. The Types associated with Sulfur seem incorrect.  All specify R- groups,
which I assumed to be -C-???, but there is at least one example (sulfapyridine)
which has S(O2)-N- bonding...  Should the sulfur groups be "any atom"
connections, or am I misunderstanding the terminology throughout?

I realize this is a large number of questions, but they're basically the same
kinds of problems.  I think folks have implemented this model in their work
(and if Arup and/or Gordon are lurking, I'd appreciate their input!), so there
should be some expertise out there - how folks have resolved these ambiguities.

Thanks in advance - I welcome all comments!  Please flame me directly, unless
they're particularly interesting (I've always hated reading boring flames).

Joe

-- 

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Joe Leonard
Wavefunction Inc.
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