Subject: hydrogen bonding...

From: Kevin Moore <[email-masked]>
Date: Mon, 3 May 93 16:17:39 EDT

Hello-
     I am doing some ab initio calculations on a couple of molecules to
determine the chemical shifts of a few protons. The results for one molecule
are not coming as close to experiment as I had expected. In response to
this, I was hoping to strategically position one or two waters in a manner
that would satisfy the H-bonding that the system is probably doing in
solution. I know that some work has been done on looking at water x-mers
and related, but was wondering if there has been any work looking at
secondary amines? On a more fundamental level, how would one approach the
problem of best orienting one or two waters in relation to a molecule
such as pyrrolidine. I have received suggestions of sticking it in
a water box, minimize and then do dynamics and look at which h2o seem to
stick closest to the molecule in the dynamics. Any other ideas? Is this a
reasonable way to get started? I am trying to minimize the CPU time involved
with generating the HF minimized structure for this type of system (the
actual molecule is larger than pyrrolidine).

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
||  Kevin Moore                      North Carolina Supercomputing Center   ||
||  Scientific Support Analyst       3021 Cornwallis Rd.                    ||
||  (919) 248-1179                   Research Triangle Park, NC 27709       ||
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

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From: "DR. DOUGLAS A. SMITH, UNIVERSITY OF TOLEDO" <[email-masked]>
Date: Mon, 03 May 1993 23:06:41 -0500 (EST)

>actual molecule is larger than pyrrolidine).

We recently published a paper (JACS 1993, 115, 2912) entitled "Theoretical
Studies on Hydration of Pyrrole, Imidazole, and Protonated Imidazole in the
Gas Phase and Aqueous Solution".  While these compounds are not secondary
amines but rather aromatic, the general approach is, I think, what you 
are after.  We looked at these molecules at the HF/6-31G* and MP2/6-31G*
levels for total geometry optimization both in gas phase and hydrated
(one molecule of water per solute, position optimized either in the plane
or above the plane of the solute; two molecules of water as well for 
imidazole).  Single point calculations were carried out at the MP2/6-311++G**
//MP2/6-31G* level and combined with frequency analyses and BSSE corrections
at the MP2/6-31G* level to calculate the free energies of hydration.

In addition, we carried out Monte Carlo simulations using Jorgensen's Boss
3.1 program for dilute aqueous solutions in order to determine the hydrogen
bonding geometries and free energies.  The MC results were also analyzed
using radial distribution functions.

To answer your question as to how to best orient one or two water molecules
around such molecules, the best answer is 1) look at what is already in the
literature, such as our paper or others with more relevant systems to your
own, and start from the reported optimized positions; 2) take your best 
guess based on solid chemical intuition, then optimize both in plane and
out of plane; 3) triple check everything.  For instance, we tried to look
at imidazole with one water in the plane making a sigma hydrogen bond and
a second water in the pi region.  However, all attempts led to a structure
in which one water formed a sigma hydrogen bond while the second water
formed a hydrogen bond to the first water.

We are now writing up our results of similar studies on histamine.

Last piece of advice - these are big, _expensive_ calculations if done right,
which includes perturbation or correlation during the optimization, and
at a basis set level sufficient to describe hydrogen bonding, i.e. at least
6-31G* or DZP, with at least one set of diffuse functions.  The latter
are extremely important, as shown by our results and those of others,
such as Janet Del Bene.

On another note, let me plug the symposium on Modeling the Hydrogen Bond, 
which I am chairing at the Chicago ACS meeting in August.  It will run
two full days, Sunday and Monday, and will include a number of big names
and forefront research in this area.

Doug

Douglas A. Smith
Assistant Professor of Chemistry
The University of Toledo
Toledo, OH  43606-3390

voice    419-537-2116
fax      419-537-4033
email    [email-masked]

P.S.  reprints of our article are available by request - email or US mail.