Abstract

We have focused our attention on the electrostatic properties of a set of PCDDs, polychlorinated dibenzo- p-dioxins, of known binding affinities for the Ah receptor. In this paper we analyze the molecular electrostatic potential (MEP) of the six selected isomers, 2,3,6-TrCDD, 1,2,4,7,8-PeCDD, 1,2,3,4-TCDD, 1,2,3,4,7-PeCDD, 1,2,4-TrCDD and 1-MCDD, in order to validate the results previously obtained on a test set of eight PCDDs. A visual analysis of the MEP distributions shows that the stepwise differentiation from the electrostatic characteristics typical of the most active isomers is associated with a decrease in binding affinity; however, the simultaneous occurrence of different trends for different electrostatic requirements for activity does not make for a simple definition of the relationships between MEP patterns and affinities for the whole set of isomers. The information retained in the overall MEP distributions is summed up in a few carefully chosen descriptors, i.e. the MEP values in particular points located around the molecules. A statistical analysis performed by linear and non-linear methods elucidates the electrostatic requirements effective in the recognition process with the Ah receptor; from this there also emerges a physical interpretation of the process. In particular, two different types of electrostatic feature associated with two subsets of PCDD isomers appear to be recognized by the Ah receptor.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call