Subject: Re: CCL:Energies of conformations

From: "Peter Shenkin" <[email-masked]>
Date: Thu, 12 May 1994 11:39:07 -0400

On May 10,  4:58pm, Wilson_Bruce wrote:
> Subject: CCL:Energies of conformations

> Patrick Bultinck asks:
> > I would like to hear different opinions to how to more or less draw a
> > line between confomers that may show an ***important*** occupation at a
> > temperature T, and which conformers do not show any ***important***
> > occupation! I have thusfar found a number of quite contradictory
> > statements, and would like to hear other peoples opinions.

> Sure, I'll wade in with a very equivocal answer:  "It depends!".
> Seriously.  If the Boltzman distribution shows a 1% population of
> a conformer level, that may be insignificant for some applications, but
> it may be highly significant for others.  But the simple answer is that
> I'll do a Boltzman analysis...

Another thing that people sometimes forget:  this depends on the density
of states as well as the energy difference.  For example, suppose in
a conformational search one locates a particular conformer which is
kT in energy above the minimum found;  let's also assume that the
search was exhaustive, and the the minimum found really is the global
minimum.

All one can deduce from the information I've given so far is that
the higher energy conformer is present to the extent of about 37%
(that is, exp(-1) ) of the lower-energy conformer.  If these were the
only two conformers present the two percentage occurrences would
be 1/1.37 and 0.37/1.37, or 73% and 27%.  I have seen people make
statements like, "This conformer had energy kT above the global
minimum, and is therefore present 27% of the time."

Of course, if there are many other conformers, all of them will be
populated to some extent, and the figure of 27% will be a gross
overestimate;  this is particularly true when the region between
the global minimum and kT above it is densely populated.

Bruce's Bolzmann analysis would take this into account; I mention
it because in casual discussion it is sometimes forgotten.

Also, a comment on Patrick's term, "*** important ***".  When trying
to figure out what is important, it is best to think in terms of
experiment.  If you are looking at proton NMR data, then each proton
has the same "extinction coefficient", and a species present at less
than 1% in total concentration may not even be visible if there are
several other species present.  Thus, if you are comparing your
computation with NMR data, 1% might be unimportant.  But if you are
using UV spectroscopy, that species might have an extinction coefficient
1000 times greater than some other species which is present at 100 times
its concentration -- so here, that 1% would be highly important.
Similarly, if the assay is biological, a low-concentration isomer might
be the only one that is active.

	-P.

-- 
*********** After the revolution, everyone will have a home page. ***********
Peter S. Shenkin, Box 768 Havemeyer Hall, Dept. of Chemistry, Columbia Univ.,
New York, NY  10027;     [email-masked];     (212) 854-5143
*****************************************************************************

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From: Gustavo Mercier <[email-masked]>
Date: Thu, 12 May 1994 13:27:28 -0400 (EDT)

One final comment ...

If you wish to compare with experiments, you must use the appropriate
Free Energy in your Boltzman population analysis. It is "common" to
compute internal energy and "forget" about the entropy.

gus mercier
[email-masked]