Subject: ZINDO/1 estimation of delta E on bond compression

From: "Helder Marques" <[email-masked]>
Date: Mon, 21 Feb 2000 07:06:48 +0200

Dear CCLers,

It is postulated that one of the mechanisms used by the 
coenzyme B12(AdoCbl)-dependent enzymes to catalyse the 
homolysis of the Co-C bond (the first step in the catalytic cycle) 
is mechanochemical triggering where upward flexing of the corrin 
ring by compression of the Co-N axial bond to the base 
benzimidazole in the class II enzymes (or His in the class I 
enzymes) causes weakening of the Co-C bond.  There are two 
possibilities here.  Either the enzyme destabilises the ground state 
by upward flexing of the corrin ring so sterically weakening the 
Co-C bond, or stabilises the transition state.  In the transition 
state version of mechanochemical triggering, the axial Co-N 
bond is sterically compressed in the transition state, to provide 
electronic stabilization through increased ligand-metal orbital 
overlap.

The strain energy consequences of stretching the Co-C bond in 
AdoCbl to simulate the approach to the transition state, and of 
compressing the Co-Nax bond can be determined using 
molecular mechanics methods with a force field that we have 
developed and extensively tested and which accurately and 
reliably reproduces many of the structural features of these 
compounds.

In order to estimate the electronic effect of Co-Nax bond 
shortening in the transition state we proceeded as follows.  I would 
like your comments on our approach.  Are the energy values we 
obtain likely to be reliable?  In particular, I would be grateful if you 
could point me to appropriate references.

To save computational time, AdoCbl was edited to truncate all 
side chains of the corrin ring to methyl groups, and a proton was 
substituted for the ribose at the non-coordinated N of the 
benzimidazole axial base.  Hydrogens were placed in standard 
positions and the structure was energy minimized using the 
molecular mechanics force field. 

The Co-C bond length was then fixed at 2.5, 2.8, or 3.2 A (to 
simulate possible positions of the transition state for Co-C bond 
homolysis), while the Co-Nax bond length was varied from ca. 
2.35 to 1.70 A by changing the strain-free bond length.  Each 
model was energy-minimised using molecular mechanics.  A single 
point calculation was then performed on each model using the 
ZINDO/1 semi-empirical molecular orbital method.  The heat of 
formation of each model was obtained from this calculation and 
normalized against the minimum heat of formation found for the 
series of models with each fixed Co-C bond length.	We find that 
the relative (but not absolute, of course) heats of formation are 
quite insensitive to the Co-C bond distance.  The minimum in the 
potential energy curves is at a Co-Nax bond length of 1.96 A and 
this is also independent of the trans Co-C bond length.  From 
these data, we estimate that compression of the Co-Nax bond 
from 2.23 (the value in the ground state, obtained from the X-ray 
structure) to 1.96 A in the transition state for AdoCbl homolysis 
results in a stabilization of about 10 kcal mol-1  due to improved 
overlap between the metal and the coordinated nitrogen. 

With thanks

Helder Marques

__________________________________________________________
Professor Helder M Marques
Head: Department of Chemistry
University of the Witwatersrand
PO Wits
Johannesburg
2050 South Africa
Tel +27+11+716-2303
Fax +27+11+339-7967
http://www.chem.wits.ac.za