Subject: Re: CCL:MM calc's of stereoisomers

From: "Dr. Tom Pierce" <[email-masked]>
Date: Tue, 19 Apr 1994 16:11:07 +22305458 (EDT)

Previously, Matthew Stahl wrote:
> 	Is it appropriate to apply molecular mechanics to the
> determination of the relative stability of two stereoisomers?
Yes. And the results had better be identical. If they are
mirror-images then the energies should be exactly the same. 

Assuming your minimizer minimizes correctly.

> words, if a single stereocenter is inverted, should I be able to calculate
> which one is more stable? 

Potentially a different question. If a sterocenter is inverted,
then you do not necessarily have a mirror image. And you may
get different energies. Mechanics is normally applied to R and S
isomers. 

> Mechanics is normally applied to conformational
> isomers, but not configurational isomers.  Where do stereoisomers fit into
> the picture? 

They are the analyzed the same way. Note that small differences in 
conformational energies are probably not accurate in MM forcefields. 
(say .5 kcal or less) 

Fancier calculations (semi-empirical or QM ) without using 
symmetry might give better answers. 

-- 
Sincerely, Thomas Pierce - [email-masked]  -  Computational Chemist
"These opinions are those of the writer and not the Rohm and Haas Company."

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From: tj ODonnell <[email-masked]>
Date: Tue, 19 Apr 1994 15:22:07 -0500 (CDT)

There can be no difference in energy between stereoisomers in the
molecular mechanics approximation.  Think of it like this:
all energies depend on pairs of interatomic distances and
the inversion of a center does not change (the matrix of)
interatomic distances.

TJ O'DOnnell
[email-masked]

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From: David Maxwell <[email-masked]>
Date: Wed, 20 Apr 94 1:02:55 EDT

Yes, it is appropriate to apply molecular mechanics to the determination of
the relative stability of two stereoisomers.  However, you will form the
entantiomer if there is only one stereocenter and it is inverted.  "Enantiomers
have identical chemical properties except toward optically active reagents"
-Morrison & Boyd.  By definition, they will have the same internal energy.  If
there are other stereocenters present, then the physical properties can change.

Please refer to a chapter on stereochemistry in a suitable chemistry book for
more information.

-Dave Maxwell ([email-masked])

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From: Rami Osman <[email-masked]>
Date: Wed, 20 Apr 1994 10:04:54 -0400 (EDT)

Hi Mathew,
   Naturally, the answer is NO. You will not be able to distinguish between two
stereoisomers, because the energy expression does not depend on the streochem-
istry of a single chiral atom. It actually doesn't matter which Hamiltonian
you use, i.e., quantum mechanical or molecular mechanics. The only thing that
distinguishes btween the steroisomers (I assume they are enantiomers) is their
interaction with polarized light, and this is not part of the Hamiltonian.
   Good Luck with the rest of the calculation,
                                              Roman Osman

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From: [email-masked]
Date: Wed, 20 Apr 1994 10:40:05 -0400 (EDT)

Hi Matt,

You've probably received a bunch of replies to your question already, but
I'll put my 2 cents in anyway.

If the isomers in question are true mirror images, then their physical
properties (heat of formation, boiling point, etc.) are identical, so the
stabilities of the two stereoisomers are the same.  This is due to
symmetry, and has nothing to do with what computational method you happen
to be using.

Regards,
Greg

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