RE: QSAR - Looking for a pKa Prediction Program

One method of predicting the macroscopic pKa's of multi-protic compounds
that is receiving some attention is through the use of the Ising
model. The Ising model is a statistical mechanical approach originally
developed to treat gas adsorption phenomena to solid surfaces. It has been
extended to describe the acid-base behavior of linear and non-linear
polyelectrolytes. In general its application has been limited to compounds
with a uniform type of functional group, but has also been extended to
treat more complex cases. The interested reader can view the following
references for greater detail:

1) Borkovec et al. Proc. Natl. Acad Sci. 94: 3499-3503 1997

available at http://www.clarkson.edu/~borkovec/daicic1.pdf

2) van Duijvenbode et al. Phys Chem Chem Phys 1: 5649-5652 1999

available at http://www.stanford.edu/~duijvenb/pccp.pdf

3) van Duijvenbode et al. Macromolecules 33: 46-52 2000.

available at http://www.stanford.edu/~duijvenb/macromolecules.pdf

4) Borkovec M. Langmuir 13:2608-2613 (1997).

  Available at http://www.unige.ch/cabe/borkovec/preprints.htm

At 11:52 AM 2/21/2003 +0000, you wrote:
>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
>--
>-----------------------------------------------------------------------------------
>Mark Earll CChem MRSC Umetrics
>Senior Consultant (Scientific Data Analysis)
>Umetrics UK Ltd
>Woodside House, Woodside Road,
>Winkfield, Windsor, SL4 2DX
>
>Phone: 01344 885615 Mobile: 07765 402673
>Email: mark.earll###umetrics.co.uk
>Fax: 01344 885410
>Web: <http://www.umetrics.com/>http://www.umetrics.com
>--------------------------------------------------------------------------------------
>
>-----Original Message-----
>From: Lipnick.Robert],[epamail.epa.gov [mailto:Lipnick.Robert|epamail.epa.gov]
>Sent: 19 February 2003 19:15
>To: qsar_society+/-accelrys.com
>Cc: 'qsar_society() 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
>ICC Building
>1201 Constitution Ave., N.W.
>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%abbott.com [mailto:yvonne.c.martin:+:abbott.com]
>Sent: 13 February 2003 17:33
>To: qsar_society . 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

Regards,
Mario J. Citra Ph.D.
Syracuse Research Corporation
(315) 452-8406
citra:-:syrres.com
http://esc.syrres.com/
Received on 2003-02-27 - 07:33 GMT