Subject: conformational isomers - annotated synopsis

From: Mick Kappler <[email-masked]>
Date: Thu, 23 Feb 1995 13:58:25 PST

On Tue, 21 Feb 95 4:08:12 EST, Dongchul Lim wrote:

> Is there a simple way of testing if two given conformational isomers
> are equiva
lent?

This question can be interpreted in two ways, as Joel Polowin indicated.

On Wed, 22 Feb 95 10:29:54 -0500, Joel Polowin wrote:

> I don't think the situation is quite so simple -- possibly depending on
> what is meant by conformers being "the same".

If one is interested in structural equivalency independent of conformation,
the SEMA algorithm (JACS, 96, 4834, 1974) is a solution.  If one is interested
in structural equivalency dependent of conformation, the solution is more
complex, as Marvin Waldman pointed out.

On Wed, 22 Feb 1995 14:47:42 -0800, Marvin Waldman wrote:

> This is, in fact, quite a difficult and subtle question.  The SEMA
> algorithm which Mick Sappler proposed can be used to detect if
> two CONFIGURATIONAL isomers are equivalent (ie. they have the
> same or different stereochemistry).  However, it will not detect
> if the same configurational isomers are equivalent or not in
> a CONFORMATIONAL sense.  SEMA cannot detect the difference between
> the gauche and trans forms of n-butane.  These are CONFORMATIONAL
> isomers.

This is correct.  The ultimate solution to the structural equivalency dependent
of conformation problem will depend on analytical features of the two
structures only.

On Thu, 23 Feb 1995 01:47:29 EST, CBAS25 ::P_BLADON ::CBAS25 wrote:

> There are several points to consider.
>
> (1) If the problem involves small molecules like butane where the number
> of stable conformers is known...

We can not assume we have anything but the two conformations that we wish to
compare.  Given a hypothetical structure, who knows the set of stable
conformers?

> (2) If the structures are more complex... then the number of conformers
> could be large.  But suppose that you have a set of such structures...

Again, let's not assume we know.

> (3) To do the matching you could use atom to atom matching...

This could take a long time, considering the size of the set of structures to
compare.  Is time an issue?  I imagine it is if you have a large set of
structures to compare.

On Wed, 22 Feb 1995 23:36:21 -0800, Victor M. Rosas Garcia wrote:

> ...The best implementation I have seen to solve this problem is in the
> program GMMX, a global minimum search utility by Serena Software.

If this works for you, this is great.  Unfortunately, this technique is only
as good as the software and comparison of conformation A by software X to
conformation B by software Y is impossible.  Hence, comparisons between
research groups may be a problem.  This is not to mention the multiple minima
problem, as E. Lewars pointed out.

On Wed, 22 Feb 1995 17:10:28 -0500, E. Lewars wrote:

> ...enantiomers have precisely the same energies...

On Wed, 22 Feb 1995 23:32:59 -0500, Graham Hurst wrote:

> The Conformational Search module of the ChemPlus set of extensions
> for HyperChem uses energy and RMS compairisons of topologically
> equivalent atom pairings.

RMS comparisons look promising at first.  Unfortunately, before the comparison
can be made, the conformations need to be superimposed, which is independent of
the conformation itself.  Although the superimposition can be solved
analytically, it is sometimes solved iteratively, and can be a source of
contention.  Can we solve this problem indepedent of transformation?

I would love to hear more from experts in this field.  This is an interesting
problem and this discussion has increased our interest in publishing our latest
work relating to conformational comparisons.

                                        Mick Kappler
                                        Molecular Engineering Laboratory
                                        W. T. Wipke Group
                                        Univ. of California, Santa Cruz