138606-34-5Relevant articles and documents
Synthesis of adducts formed by iodine oxidation of aromatic hydrocarbons in the presence of deoxyribonucleosides and nucleobases
Hanson, Aaron A.,Rogan, Eleanor G.,Cavalieri, Ercole L.
, p. 1201 - 1208 (2007/10/03)
Polycyclic aromatic hydrocarbons (PAH) undergo two main pathways of metabolic activation related to the initiation of tumors: one-electron oxidation to give radical cations and monooxygenation to yield bay-region diol epoxides. Synthesis of standard adducts is essential for identifying biologically formed adducts. Until recently, radical cation adducts were synthesized by oxidation of the PAH in an electrochemical apparatus, not readily available in many organic chemistry laboratories. We have developed a convenient and efficient method for synthesizing PAH-nucleoside adducts by using I2 as the oxidant. Adducts of benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DB[a,l]P), and 7,12-dimethylbenz[a]anthracene were synthesized with deoxyguanosine (dG), deoxyadenosine, guanine (Gua), or adenine in either Me2SO or dimethylformamide (DMF) with or without AgC104. When, for example, the potent carcinogen BP was dissolved in DMF in the presence of 3 equiv of I2, 5 equiv of dG, and 1 equiv of AgC104, 45% of the BP was converted to BP-6-N7Gua. When BP was placed under the same reaction conditions in the absence of AgC104, the extent of formation of BP-6-N7Gua decreased to 30%. When the potent carcinogen DB[a,l]P was dissolved in DMF in the presence of 3 equiv of I2, 5 equiv of dG, and 1 equiv of AgC104, 43% of the DB[a,l]P was converted to DB[a,l]P-10-N7Gua. In the more polar solvent Me2SO under the same reaction conditions, however, the yield of DB[a,l]P-10-N7Gua was only 20%. Synthesis of adducts with the oxidant I2 is more convenient and, in some cases, more efficient than synthesis by electrochemical oxidation. This method simplifies the synthesis of PAH-nucleoside and nucleobase adduces that are essential for studying biologically formed PAH-DNA adducts.
Synthesis and structure determination of the adducts of the potent carcinogen 7,12-dimethylbenz[a]anthracene and deoxyribonucleosides formed by electrochemical oxidation: Models for metabolic activation by one-electron oxidation
Ramakrishna,Cavalieri,Rogan,Dolnikowski,Cerny,Gross,Jeong,Jankowiak,Small
, p. 1863 - 1874 (2007/10/02)
Anodic oxidation of 7,12-dimethylbenz[a]anthracene (7,12-DMBA) in the presence of dG yields four adducts and one oxygenated derivative of 7,12-DMBA: 7-methylbenz[a]anthracene (MBA)-12-CH2-C8dG (13%), 7-MBA-12-CH2-N7Gua (55%), 12-MBA-7-CH2-N7Gua (12%), 7-MBA-12-CH2-C8Gua (10%), and 7,12-(CH2OH)2-BA (10%). The first three are primary products of the electrochemical reaction, whereas the last two are secondary products. Binding occurs predominantly at the 12-CH3 group of 7,12-DMBA and specifically to the N-7 and C-8 of Gua. On the other hand, anodic oxidation of 7,12-DMBA in the presence of dA gives only two detectable adducts: 7-MBA-12-CH2-N7Ade (45%) and 12-MBA-7-CH2-N3Ade (55%). Binding at the 12-CH3 group is specific for the N-7 of Ade, whereas the 7-CH3 group of 7,12-DMBA is specific for the N-3 of Ade. Structures of the adducts were elucidated by NMR and fast atom bombardment tandem mass spectrometry (FAB MS/MS). The adducts were also investigated by fluorescence line narrowing spectroscopy (FLNS). Both the FAB MS/MS and FLNS techniques can be used to distinguish between the adducts formed at the 7-CH3 and 12-CH3 groups of 7,12-DMBA (i.e., between 7-MBA-12-CH2-N7Gua and 12-MBA-7-CH2-N7Gua and between 7-MBA-12-CH2-N7Gua and 7-MBA-12-CH2-C8Gua). FLNS can distinguish 12-MBA-7-CH2-N3Ade from 7-MBA-12-CH2-N7Ade. On the other hand, the distinction between 7-MBA-12-CH2-C8Gua and 7-MBA-12-CH2-C8dG is straightforward by FAB MS but very difficult by FLNS. The electrochemical synthesis not only provides a demonstration of the specific reactivity of nucleosides and 7,12-DMBA under oxidizing conditions but is also a source of the necessary reference materials for studying the 7,12-DMBA-DNA adducts formed in biological systems. Furthermore, the analytical methodology is now appropriate for supporting in vivo studies of 7,12-DMBA-DNA adducts. A mechanism is proposed, although there are not sufficient data to prove it.
