How to calculate the Woodward Height of pyramid parameter 'h' for N-atom and Cohen parameter 'c' for beta-lactam rings and their derivatives? Is there any software or web resource to get the information for any newly designed derivatives?
Dear Nagendra,
Two structural features of β-lactam antibiotics have been correlated with their antibiotic potency. The first is known as "Woodward's parameter", h, and is the height (in angstroms) of the pyramid formed by the nitrogen atom of the β-lactam as the apex and the three adjacent carbon atoms as the base. The second is called "Cohen's parameter", c, and is the distance between the carbon atom of the carboxylate and the oxygen atom of the β-lactam carbonyl. This distance is thought to correspond to the distance between the carboxylate-binding site and the oxyanion hole of the PBP enzyme. The best antibiotics are those with higher h values (more reactive to hydrolysis) and lower c values (better binding to PBPs).
To calculate h and c, you should use one of the quantum mechanics methods such as ab initio, semi-empirical or DFT methods. Alternatively, you can conduct molecular mechanics calculations (Allinger's MM).
Personally, I use DFT methods at a basis set of B3LYP/6-31G (d,p) installed in Gaussian 09 for the calculation of penicillin derivatives.
For such calculations, you need to install G 09, GaussView (ArgusLab) and Molden.
Hoping this will be helpful,
Rafik
Professor Rafik Karaman:
Thank you very much for the information on resources to calculate the h & c parameters for beta-lactams. Yes, surely this will be helpful for me. Thanks for your time once again Professor.
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