Subject: Semi-empirical S-charge: 'right' or 'wrong' ?

From: "E.E.Moret" <[email-masked]>
Date: Sun, 26 Jun 94 13:41:40 METDST

Dear colleagues,

A good scientific discussion is appropriate and let me be the first to
say that I am aware of the fact that my subject line is questionable.
There is no right or wrong charge. Atomic point charges are merely a useful
concept in computational chemistry. However, the semi-empirical charges
I have obtained for the hypervalent S atom are a problem. They disrupt
molecular mechanics calculations that I want to perform. I face the
problem of accepting these charges or considering them useless for
my purpose (docking). Here is my dilemma:

We are currently studying molecules with around 100 atoms of which
a sulfonamide group is of relevance. Apart from a geometry that does not 
correpond to X-ray and ab initio information, we observe large positive
charges on the S atoms. 
Some calculation results on the molecule CH3-SO2-NH-CH3 follow.
The C-S-N-C torsion angle in the input file was close to the
ab initio and X-ray data of 70 or -70.

I used MINDO3,MNDO,AM1,PM3 Hamiltonians in Ampac 2.1, Mopac 5, Mopac 6 and 
Mopac 93. The partial charge on the S atom varied between 1.6 and 2.6 !
Fortunately, there was no programme dependency, apart from programmes that
explicitly mentioned the use of a different Hamiltonian for one element.

This would be a typical result for the S-charge (Mopac93):

sulfa_opt_MINDO3:        6          S           1.849085     
sulfa_opt_MNDO:          6          S           1.632472      
sulfa_opt_AM1:           6          S           2.526724    
sulfa_opt_PM3:           6          S           2.159568       

The input-file with cartesian coordinates is appended at the bottom.
Besides interesting geometry and charge, the bond orders for the bonds from
S to C or N are typically 0.7, whereas the bond orders for the bonds
from S to O are 1.15.

I consider the system size prohibitive for ab initio calculations and I hesitate
to use an empirical charge calculation. I would value your input
on the following questions:
- am I wrong in considering the current results conspicuous?
- should I accept the current charges, geometry and bond orders?
- should I turn to more rigorous or more empirical methods?
- should I fiddle the current charges (i.e. changing the S valency by hand and
substracting some pos. charge of S and some neg. charge of its neighbouring
atoms, which would be a manual reduction?
- are their experimental data which would allow me to check whether the current
results predict the right interaction or behaviour of S-containing compounds.
- will the P atom give comparable results?

For those who noticed that I avoided naming P and S. Is it a phosphorus atom and
a sulphurous atom or is sulphur and phospor correct english?

I am looking forward to your ideas on this topic.

With best regards,
Ed Moret
-------------------------------------------------------------------------
E.E. Moret	(@more@)			    [email-masked]
Computational Medicinal Chemistry/Department of Pharmaceutical Chemistry
Faculty of Pharmacy/Utrecht University/the Netherlands
Telephone	(31-30)536979/536958        Facsimile      (31-30)516674
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AM1 T=3600 NOINTER PRECISE BONDS 
./sulfa_opt_AM1.dat
 
0001 0.0000    0000 0.0000    0000 0.0000    0000 0000 0000 0000
0001 1.7964    0000 0.0000    0000 0.0000    0000 0000 0000 0000
0001 1.4572    0000 3.3222    0000 0.0000    0000 0000 0000 0000
0001 3.5945    0000 3.7754    0000 0.5259    0000 0000 0000 0000
0006 0.8982    0000 0.1420    0000 0.6190    0000 0000 0000 0000
0016 0.8981    0000 1.7989    0000 1.3224    0000 0000 0000 0000
0007 1.6790    0000 3.0433    0000 1.0195    0000 0000 0000 0000
0006 3.1526    0000 2.9846    0000 1.1500    0000 0000 0000 0000
0001 0.8982    0000 -0.5819   0000 1.4472    0000 0000 0000 0000
0001 3.5287    0000 2.0089    0000 0.8086    0000 0000 0000 0000
0001 3.4511    0000 3.1472    0000 2.1961    0000 0000 0000 0000
0008 0.4152    0000 1.4318    0000 2.6394    0000 0000 0000 0000
0008 -0.3714   0000 2.2528    0000 0.7887    0000 0000 0000 0000