Subject: pKa Calculation summary

From: "CBAS25 ::P_BLADON ::CBAS25" <[email-masked]>
Date: Mon, 30 Jan 1995 15:28:20 EST

Dear Colleagues,
	Here as promised is the summary of the responses I got from the
enquiry on calculation of pKa values.   Very many thanks to all who replied
to this.  I had looked at the archives but it is obvious that I missed the
recent enquiry on a similar topic.  I shall be looking into the the avenues
afforded by the replies. 
Yours sincerely
Peter Bladon

First the enquiry I made:
______________________________________________________________________________
>Dear Colleagues,
>I am writing to ask if anyone knows of software for calculation of pKa 
>values of organic compounds.  Ideally I would like to calculate the full 
>range of organic structures, but if necessary it could be applicable
>to structures with conventional ionizable groups.  Methods using
>addition of functional group parameters would be ideal.
>
>If there is any interest in this topic I will summarise for the group.
>Yours sincerely
>Peter Bladon

>Department of Pure and Applied Chemistry
>University of Strathclyde
>Glasgow G1 1XL   Scotland   UK
>[email-masked]
>Phone/Fax (+44)(0)141-776-1718
______________________________________________________________________________
From:	MX%"[email-masked]" 

Dear colleague,
please try the demo version on
gopher://www.ccl.net:73/11/software/MS-WINDOWS/pKa_logP_logD-demo
This can also be reached via WWW as http://www.ccl.net/chemistry.html
(software archive MS-Windows).
Kind regards,
Christine Rudolph

Dr. Christine Rudolph				phone: ++49 - 6130 - 911 - 403
Molecular Modelling				fax:   ++49 - 6130 - 911 - 113
Cyanamid Forschung GmbH				e-mail:[email-masked]
Zur Propstei
55270 Schwabenheim
Germany
______________________________________________________________________________
From:	MX%"[email-masked]" 

I asked the same question a few months ago and I am forwarding you a reply (the
only one) that I got. Hope this helps.

		Ela Wilinska
""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""
>From:	MAIL1::"[email-masked]" 

>If you can send the structures, we have a reasonable 
>pKa calculator (pka's in water). The SMILES string 
>if you're familiar with it would be best.

>Butch Carreira                             [email-masked]
Department of Chemistry                    (706) 542-2050 or 2051
>The University of Georgia                 (706) 542-9454 FAX
>Athens, GA  30602
""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""
______________________________________________________________________________
From:	MX%"[email-masked]" 

Dear Peter,
        There is a peer-reviewed  pKa calculater appropriately called pKalc
by CompuDrug.  I will be sending you a demonstration diskette as well as
marketing and spec information to your adress posted.  This package is
available to ACs members for 695 through the ACS order department.  I will
send you a complete catalog and ordering information as well. Hope this
helps!  NB
______________________________________________________________________________
From:	MX%"[email-masked]"

Peter,

	Check the archives of this list. I think that this was discussed
not too long ago. I think that the best one for your purposes is CAMEO
written by the Jorgensen group at Yale University.

Adi T.

______________________________________________________________________________
From:	MX%"[email-masked]"

Dear Peter,

I don't know of software, but here are two references
of possible interest.  I would guess that the authors
could make their programs available.

@Article{dixon_pka,
  author = 	 "Steven J. Dixon and Peter C. Jurs",
  title = 	 "Estimation of p{K}a for Organic Oxyacids using
		  calculated atomic charges",
  OPTcrossref =  "",
  OPTkey = 	 "",
  journal = 	 "J. Comput. Chem.",
  year = 	 "1993",
  volume = 	 "14",
  OPTnumber = 	 "",
  pages = 	 "1460-1467",
  OPTmonth = 	 "",
  OPTnote = 	 "",
  OPTannote = 	 ""
}
@Article{pka_qsar1,
  author = 	 "Gilles Klopman and Dan Fercu",
  title = 	 "Application of the {M}ultiple {C}omputer {A}utomated
		  {S}tructure {E}valuation methodology to a
		  quantitative structure-activity relationship study
		  of acidity",
  OPTcrossref =  "",
  OPTkey = 	 "",
  journal = 	 "J. Comput. Chem.",
  year = 	 "1994",
  volume = 	 "15",
  OPTnumber = 	 "",
  pages = 	 "1041-1050",
  OPTmonth = 	 "",
  OPTnote = 	 "",
  OPTannote = 	 ""
}

Good luck,

Mike Gilson
Center for Advanced Research in Biotechnology
[email-masked]
______________________________________________________________________________
From:	MX%"[email-masked]"

Peter,

I would appreciate hearing any replies that you get to your message
about pKa calculations.  Thanks.

Ed Jaeger ..... em: [email-masked] -- 
______________________________________________________________________________
From:	MX%"[email-masked]"

Let me know what you find.  The one thing I know about is CAMEO from Bill
Jorgensen's group. I haven't tried it out, but am about to do so.

Yvonne Martin
Abbott Laboratories
______________________________________________________________________________
From:	MX%"[email-masked]"

This topic was discussed and I believe summarized recently on this list
(in the last 6 mos?).  Check the archives.

Kimberley Cousins
Department of Chemistry
California State University, San Bernardino
5500 University Parkway
San Bernardino, CA  92407

(909)880-5391
[email-masked]
______________________________________________________________________________
From:	MX%"[email-masked]" 

Peter 

I would like to have a copy of your responses to the pKa question.

Thanks
__________________________________________________________
Jerry L. Born Ph. D.
Professor of Pharmacy			Voice (505) 277-3657
The College of Pharmacy			Fax     (505) 277-6749
The University of New Mexico		Email   [email-masked]
Albuquerque, NM 87131
__________________________________________________________
From:	MX%"[email-masked]" 

There was a request for info on the calc of pKa on the Comp Chem Net about 6-
12 months ago; the results may be in the archives, which you can search.
I have some refs to the calc of pKa, and will be happy to send them to you
if you're interested: M. J. S. Dewaret al used AM1 to calc scidities, i.e.
pKa, in a paper in JACS ca. 1986.  Also, the calc of pKa is described in
*Experiments in Computational Organic Chemistry*, byHehre, Burke,
Shusterman and Pietro, published by Wavefunction, Inc, the company that 
makes the Spartan computational chemistry program.  If you have Spartan,
calculating pKa from electrostatic potentials should be quite easy.  Try
to get hold of Spartan and this book.  If you can't get the book, I 
could send you Xerox copies of the relevant parts.
Good Luck
(Prof) Errol Lewars
[email-masked]
______________________________________________________________________________
From:	MX%"[email-masked]" 

Please do summarize...I would be interested in seeing it.  Thank you.

Wally

Walter E. Reiher III, Ph.D.                            [email-masked]
Consultant in Computational Chemistry
P.O. Box 61056                                        voice 408-720-0240
Sunnyvale, CA 94088                                     fax 408-720-0378
______________________________________________________________________________
From:	MX%"[email-masked]" 

You may want to try CompuDrug Chemistry Ltd in Budapest.

Their e-mail address is [email-masked]

and the programme they sell is called pKalc.  I've looked at a demo 
version and it seems very useful.

Prof. Helder M. Marques, Department of Chemistry
University of the Witwatersrand, P.O. Wits
2050 Johannesburg,
South Africa
Fax: Int + 27 + 11 + 339-7967
______________________________________________________________________________
From:	MX%"[email-masked]" 

Peter, 

Our group has been working on a program to calculate ionization pKa's.
Currently the only module we have is a PC-Windows winsock client that
accesses a server in our dept. We have tested the system on ~4000 IUPAC
approved pKa's with an RMS of ~0.36. The program can also calculate all
possible microconstants and generate speciation as a fn of pH curves.
I can 
   1) Send you the testing results and references to the calculator.
   2) If the number of molecules is less than 20-30, I would
      be willing to do the calculations and/or speciation plots
      for you.
   3) Make the winsock client available to you for testing.

Let me know if you are interested.

Butch Carreira
Department of Chemistry                    (706) 542-2050 or 2051
The University of Georgia                  (706) 542-9454 FAX
Athens, GA  30602
______________________________________________________________________________
From:	MX%"[email-masked]"

This is a real problem for us, and I would appreciate a summary of any 
replies you get.  My own experience:

_Delta_ pKa can be estimated in the DelPhi module marketed by Biosym, if 
their advertising can be believed.  I haven't experience with this program, 
but the blurbs sent out are reasonably impressive.

We have in the past tried to use a correlation approach, using a number of 
model compounds of known pKa, and calculating and correlating these with 
heats of formation of the acid and anion.  I usually use AM1 for this, but 
the results are at best mixed, and for the most part, I don't consider them 
reliable (these are all gas phase).  We are extending some studies to the 
AMSOL SM2 model, and I am optimistic that this will be more successful.  In 
neither case, however, do I expect an absolute pKa to be obtained, but only 
grist for a correlation.

sb
  Stephen B. Bowlus, Ph.D.                Computer-Aided Molecular Design 
                                          Research Division
  e-mail: [email-masked]               Sandoz Agro, Inc.
  Phone:  + 1 415 354 3904                975 California Ave.
  Fax:    + 1 415 857 1125                Palo Alto, CA 94304
______________________________________________________________________________
From:	MX%"[email-masked]"

Dear Dr. Bladon,

I am responding to let you know that I am interested in the summary that
you suggested.

Thank You,
John West
[email-masked]
______________________________________________________________________________
From:	MX%"[email-masked]"

Please summarize!  Thanks.

* D. Eric Walters, Ph.D., Associate Professor, Biological Chemistry
* Finch University of Health Sciences/The Chicago Medical School
* 3333 Green Bay Road, North Chicago, IL  60064
* ph 708-578-3000, x-498;fax 708-578-3240; email: [email-masked]
______________________________________________________________________________