Subject: Re: CCL:Interaction energy in host-guest complex

From: [email-masked] (Per-Ola Norrby)
Date: Fri, 23 Feb 1996 10:43:12 +0100

Dear Paolo,

        The comparison you want to make is correct, as long as no new
covalent bonds are formed between the guest and host.  The bond-specific
enthalpy contributions will all cancel out.  As you stated, you will only
get the steric component in the gas phase from this comparison (closely
related, but not identical to the enthalpic component).  My gut feeling in
this is that the most serious error in this would be the neglect of
solvation.  However, you should also be aware of the risk of
entropy-enthalpy compensation:  To make it short, the entropy difference
will probably give a significant contribution OPPOSITE to that of the
enthalpy.  For a short summary on this subject, see: J.D.Dunitz, Chemistry
& Biology, 2(11), 709-712, 1995.
        If you are comparing to experimental enthalpies, you mainly have to
worry about the solvation part (there are several good computational
approaches), but if you are trying to correlate binding constants at one
temperature, you will definitely have to take a look at the above article.
The really bad part of this is that it's pretty hard to estimate the
entropy contribution from a weak interaction computationally.

        PeO Norrby

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 *  Per-Ola Norrby
 *  The Royal Danish School of Pharmacy, Dept. of Med. Chem.
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