RE: QSAR - Looking for a pKa Prediction Program

Yvonne, John and Bob,
 
From my time in the lab measuring pKa's, I have always found that a 'by
analogy' estimation of pKa using the Perrin pKa books the best approach! It
is a great pity these books are out of print. I was not aware of the
MicroQSAR program, I would be interested to hear more.
 
I have used a few of the other programs in the past and they can work well
for single pKa values. Predictions for Multiprotic molecules are often
hopeless. An approach that can work well is to gather some analogous
molecules with known pKa's, put them through one of the cheaper molecular
property calculation packages and then build a PLS model on the output.
Unknowns with similar structures can then be predicted quite well. This
works quite nicely due to the model being built over a small area of
chemical property space but more ambitious universal models can be
problematic.
 
Is anyone working on reliably predicting multi-protic pKa's? I think this
must be a tricky hierarchical problem as the new electronic structure of the
protonated (or deprotonated) form must be taken into account for the second
or subsequent pKa. The problem gets worse with zwitterions, especially
flexible ones with internal H-bonding potential! (then its time to dust off
that electrode and head back to the lab....)
 
Mark

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Mark Earll CChem MRSC          Umetrics
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Umetrics UK Ltd                   
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-----Original Message-----
From: Lipnick.Robert===epamail.epa.gov [mailto:Lipnick.Robert]^[epamail.epa.gov]
Sent: 19 February 2003 19:15
To: qsar_society/a\accelrys.com
Cc: 'qsar_society!A!accelrys.com'; qsar_society-admin[#]accelrys.com
Subject: RE: QSAR - Looking for a pKa Prediction Program
John and Yvonne, 
We are just recovering from a major snowstorm, so if there are more recent
messages that make this obsolete, please ignore it. 
The program that Bob Hunter wrote, if I am correct, was based upon the
Perrin pKa book that I found extremely useful for doing these calculations
by hand. 
I made this know to Gil Veith and others at the EPA lab in Duluth, MN at the
time, and I think they found funds for Bob Hunter to wrote the program. 
I don't have a copy myself, but would be interested in getting one, if it
runs on a a PC. 
Bob 
===================================
Robert L. Lipnick, Ph.D.
U.S. Environmental Protection Agency
Office of Pollution Prevention and Toxics (7403M)
ICC Building
1200 Pennsylvania Ave., N.W.
Washington, DC 20460
TEL 202-564-7632
FAX 202-564-7450
lipnick.robert+*+epa.gov
For FEDEX, etc. or visits:
Dr. Robert L. Lipnick
U.S. Environmental Protection Agency
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Room 6308 LL Mail Stop 7403M
Washington, DC 20460
=================================
	Dearden John <J.C.Dearden:livjm.ac.uk> 
Sent by: qsar_society-admin%%accelrys.com 
02/14/03 04:28 AM 
Please respond to qsar_society 
        
        To:        "'qsar_society**accelrys.com'" <qsar_society:_:accelrys.com>
        cc:         
        Subject:        RE: QSAR - Looking for a pKa Prediction Program
Yvonne: 
  
The pKa software packages that I'm aware of are: 
1. Pallas from Compudrug (  <http://www.compudrug.com/> www.compudrug.com) 
2. ChemSilico (  <http://www.chemsilico.com/> www.chemsilico.com) 
3. SPARC (  <http://ibmlc2.chem.uga.edu/sparc>
http://ibmlc2.chem.uga.edu/sparc) 
4. ACD (  <http://www.acdlabs.com/> www.acdlabs.com) 
5. MicroQSAR, which was written quite a few years ago by Bob Hunter. So far
as I know, it isn't marketed any more. We have a copy, and Bob might be
willing to allow others to use it. 
  
There may well be others that I haven't come across. 
  
John Dearden 
-----Original Message-----
From: yvonne.c.martin%x%abbott.com [mailto:yvonne.c.martin- -abbott.com]
Sent: 13 February 2003 17:33
To: qsar_society/a\accelrys.com
Subject: QSAR - Looking for a pKa Prediction Program
Hi all, 
I am looking for a pKa prediction program that I can put on an internal web
page. We would take care of getting the structure in the correct form and
displaying the results. Obviously, the program must be reliable across many
structural types, be deployable in the method described above, and be
affordable. 
Replies from vendors are welcome, but please include approximate prices and
how one can test out the program. Is there a limit on the number of
structures processed? A time limit? 
Yvonne Martin 
Abbott Laboratories