Subject: CCL:Quantum charges: an opinion

From: <[email-masked]>
Date: Mon, 26 Jun 1995 12:04:00 -0400

> I would like to know what is the current opinion concerning the atomic 
> charges calculated by the quantum-chemical methods, especially for the 
> charged species. I mean their strong tendency to produce over-pronounced 
> charge separation. I might even try to reconcile myself with slight 
> negative charge on nitrogen in ammonium, but rather high POSITIVE charge 
> on carbon in (fluorinated) carbANIONS absolutely kills me.
>
> I wonder whether it might actually be computational artifact induced 
> by, for instance, improper basis set selection or atom partitioning?

>From what I can glean from the literature, most researchers seem to agree 
that HF/6-31G* MEP charges are "best" or "good" or at least adequate in 
determining atom-centered charges and there is little benefit (significant 
change in atom-centered charges) in going to MP2/6-31G* MEP charges.  
Alternatively, to save time, scaled MNDO MEP charges may be used since they 
have been shown to have a high correlation correlation to HF/6-31G* MEP 
charges, at least for CHNO compounds.  MEPs are generally preferred since 
it is argued that they reflect what is "seen", i.e., the Coulombic 
interaction experienced, by other molecules.  Atom-centered charges derived 
by partitioning methods, including emprical electronegativity balancing 
schemes such as Del Re's (avialble QCPE) and Gasteiger methods and 
semiemprical or ab initio natural atomic or Mulliken charges, are 
considered to be inferior if not unreliable.  However, recently, Cramer has 
introduced a modified Mulliken method, for, I believe AM1, which is claimed 
to reproduce MEP HF/6-31G* charges at a substantially lower computational 
cost and leading to an improved semiempirical solvation model.

As for "their strong tendency to produce over-pronounced charge separation" 
and apparently odd charges, certainly MEP HF/6-31G* charges appear to 
display more highly polarized molecules (larger atom-centered charges) than 
the partitioning methods and one may see signifcant differences in 
predicted relative charges and even charge sign changes.  But which method 
is correct?  How can one tell?  I am not aware of any correlations of 
predicted/derived atom-centered charges with direct measurements, though 
chemically modified STM may provide an opportunity to do so if the 
resolution is fine enough.  Alternatively, one might look at NMR shift 
data, but this too, includes solvation effects.  Might it be possible to 
combine NMR with MS to measure gas phase atomic environments and therefore 
the charge?  I beleive some work has been done trying to correlate electron 
denisty maps from X-ray studies with charge, but this too has a 
partitioning problems and involves crystal lattice effects.  To complicate 
matters further, derived atom-centered charges may also be conformationaly 
dependent! [There have been a few references on modifying empirical 
partitioning methods either to include through space interactions 
(Gasteiger published a variation of his method) or, I believe, to include 
conformationally dependent paramters, e.g., similar to molecular mechanics 
1-4 interactions.  Efforts have also been made to solve such equations 
directly rather than by itterative schemes so that charges may be updated 
more frequently in molecular dynamics studies].

Many would say that atom-centered charges aren't very meaningfull anyway so 
ignore them or don't worry too much.  They are an artificial, albeit 
methodical and reproducible construct, a convenience for counting or 
partitioning electrons.  But choice of charge models can have a signficant 
impact on studies particularly in molecular mechanics and molecular 
dynamics calculations in which accurate representation of intermolecular 
potentials is crucial.  

So what is a reasearcher to do?  First be consistent;  don't mix charge 
models.  Next, from a completely pragmatic standpoint, use the charge model 
which best fits your set of data.  Don't be overly concerned with absolute 
values unless there is corroborative direct or indirect evidence that they 
are "wrong" or inconsitent with other observations.

What's wrong with a negative charge on N in amonnium compounds?  That is, 
why is it important and what significance does it have?  Does it lead to 
incorrect conformations?  Presumably one might be more interested in the 
charge on the -N+H protons which might be expected to reflect H-bonding 
potential and acidity, i.e., compared with water, methanol, etc., and that, 
no doubt, has to be more positive to compensate for the negative N.

Positive C-charge on flourinated carbanions?  Why is this a problem?  Does 
it disagree with chemical reactivity, i.e., nuclephilicity of the 
carbanion?  Is it more positive than the neutral compound?

In my own work, I have also observed "bothersome" charges but more often 
than not such observations are distractions and not relevant to the study.

In the end, there is no easy answer.  This controversy is likely to go on 
for some time until methods permit us to reliably measure charges of 
individual atoms.

My appologies for not referencing the many researchers who have made 
valuable contributions to this area of research.

Karl
 _______________________________________________________________________
/                                                                       \ 
| Comments are those of the author and not Unilever Research U. S.      |
|                                                                       |
| Karl F. Moschner, Ph. D.                                              | 
|                                                                       | 
| Unilever Research U. S.      e-mail: [email-masked] | 
| 45 River Road                Phone:  (201) 943-7100 x2629             | 
| Edgewater, NJ 07020          FAX:    (201) 943-5653                   | 
\_______________________________________________________________________/