Synthesis and Rat Liver Microsomal Metabolism of 2-Chlorodibenzo[A,L]Pyrene and 10-Chlorodibenzo[A,L]-Pyrene

Abstract

Chlorinated PAHs have been identified as a class of potent genotoxic environmental contaminants. Dibenzo[a,l]pyrene (DB[a,l]P) is a potent tumorigenic environmental pollutant. In this paper, we report the synthesis, rat liver microsomal metabolism, and determination of the effect of the chloro substituent on metabolism of DB[a,l]P,2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P. The metabolism of DB[a,l]P, 2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P produced trans-8,9-dihydrodiol, trans-11,12-dihydrodiol, and 7-hydroxyl metabolites as major products. The trans-dihydrodiols of DB[a,l]P and 2-Cl-DB[a,l]P preferentially adopt a quasidiequatorial conformation, and the 10-Cl-DB[a,l]P trans-dihydrodiols adopt a quasidiaxial conformation. Based on the yield and conformation of trans-11,12-dihydrodiol, we predict the biological activities of these compounds are: DB[a,l]P > 2-Cl-DB[a,l]P ≫ 10-Cl-DB[a,l]P.

Keywords::

• Dibenzo[a,l]pyrene
• 2-chlorodibenzo[a,l]pyrene
• 10-chlorodibenzo[a,l]-pyrene
• metabolism