Re: QSAR - Looking for a pKa Prediction Program

Hi Mark et al.,

> 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....)

Tough problem. I hope that one day ab initio methods will be up to
the task on a practical timeframe.

Take a (critical) look at
http://www.schrodinger.com/Products/pka.html

Here was one of my attempts at characterising a series of multi-protic
heterocycles by this kind of technique...
http://compchem.dfh.dk/Jeremy/eccc7/

Cheers,

Jeremy
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Jeremy Greenwood jeremy#greenwood.net
Department of Medicinal Chemistry bh +45 35306117
The Danish University of Pharmaceutical Sciences fx +45 35306040
Universitetsparken 2, DK-2100 Copenhagen, Denmark ah +45 32598030
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Received on 2003-02-21 - 11:49 GMT