Synthesis and photoirradiation of isomeric ethylchrysenes by UVA light leading to lipid peroxidation.

Hui-Chan Chen,Shoujun Chen,Shu-Hui Cherng,Qingsu Xia,Ching-Cheng Lai,Hongtao Yu,Peter P Fu

doi:10.3390/ijerph2007040009

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental pollutants. We have recently demonstrated that photoirradiation of PAHs leads to cytotoxicity, DNA damage, and induction of lipid peroxidation. In this paper we report the synthesis of all the six isomeric ethylchrysenes and the study of light-induced lipid peroxidation by these ethylchrysenes. 5-Ethylchrysene was synthesized by reaction of 5-keto-5,6,6a,7,8,9,10,10a-octahydrochrysene with CH3CH2MgBr followed by dehydration catalyzed by p-toluenesulfonic acid and dehydrogenation with DDQ in benzene. 1- and 4-Ethylchrysenes were similarly prepared by reaction of 1-keto-1,2,3,4,5,6-hexahydrochrysene and 4-keto-1,2,3,4-tetrahydrochrysenes, respectively with CH3CH2MgBr followed by dehydration and dehydrogenation. Direct acetylation of chrysene followed by Wolff-Kishner or Clemmensen reduction resulted in the formation of 2-, 3-, and 6-ethylchrysenes in 4%, 16%, and 43% yields, respectively. Photoirradiation of these compounds with 7 and 21 J/cm2 UVA light in the presence of methyl linoleate all resulted in lipid peroxidation. For comparison, photoirradiation of 4-methylchrysene and 5-methylchrysene was similarly conducted. For irradiation at a UVA light dose of 21 J/cm2, the level of induced lipid peroxidation is in the order 4-methylchrysene = 5-methylchrysene = 5-ethylchrysene = 4-ethylchrysene = chrysene > 1-ethylchrysene = 2-ethylchrysene > 3-ethylchrysene > 6-ethylchrysene. Compared with chrysene, these results indicate that the ethyl group at C4 or C5 position either slightly enhances or has no effect on the light-induced lipid peroxidation, while at C1-, C2-, C3-, or C6 position reduces light-induced lipid peroxidation.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental pollutants [1,2,3]
We determined that the photoinduced lipid peroxidation by PAH is mediated by reactive oxygen species (ROS), singlet oxygen and superoxide, which are generated during the photoirradiation of PAHs [13]
We determined that the photoinduced lipid peroxidation is mediated by reactive oxygen species (ROS), singlet oxygen and superoxide, which are generated during the photoirradiation of PAHs [13]

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental pollutants [1,2,3]. Since skin is the largest body organ in humans and is unavoidably exposed to light, it is of particular importance and significance to investigate human health risks posed by exposure to the combination of PAHs and light This activation pathway has received relatively much less attention [12]. The study of the twelve isomeric methylbenz[a]anthracenes determined that the level of lipid peroxidation induced by methylbenz[a]anthracenes does not correlate with energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). These results indicate that lipid peroxidation induced by the twelve methylbenz[a]anthracenes is not directly related to their excited-state properties [13]. The results indicate that under experimental conditions, all the tested PAHs induce lipid peroxidation and the potency of lipid peroxidation depends on the position of the ethyl substitution

Methods

Results

Conclusion