Stable ion study of benzo[a]pyrene (BaP) derivatives: 7,8-dihydro-BaP, 9,10-dihydro-BaP and its 6-halo derivatives, 1- and 3-methoxy-9,10-dihydro-BaP-7(8H)-one, as well as the proximate carcinogen BaP 7,8-dihydrodiol and its dibenzoate, combined with a comparative DNA binding study of regioisomeric (1-, 4-, 2-) pyrenylcarbinols.
A stable ion study of a series of BaP derivatives is reported. 7,8-Dihydro-BaP 1 gives a persistent bay-region benzyliclike carbocation which shows extensive charge delocalization into the pyrene moiety. In contrast, a "benzylic" carbocation can not be generated from 9,10-dihydro-BaP 2. Introduction of bulky substituents at peri C-6 of 9,10-dihydro-BaP (as in 4 and 5) prevents side reactions (dimerization) to the extent that the initially formed carbocation undergoes rearrangement to generate the corresponding bay-region "benzylic" carbocation as a persistent species. Introduction of methoxy substituents into the 1- or 3-positions of 9,10-dihydro-BaP-7(8H)-one (6,7) increases its electrophilic reactivity to the extent that stable carboxonium-arenium dications are produced in FSO3H-SO2ClF. A detailed NMR study (at 500 MHz) of the resulting mono- and dications is reported, and charge delocalization mode (as well as conformational aspects) are addressed. Other oxidized derivatives of BaP such as the 7,8-dihydrodiol 9 and the 7,8-dihydrodibenzoate 8 are not suitable models for stable ion study because of competing O-protonation (and elimination). Energies for various possible arenium ions and regioisomeric "benzylic" cations were computed by the DFT method at the B3LYP/6-31G(d)//B3LYP/6-31G(d) level or by AM1 for comparison with the experimental results. These findings provide further evidence in support of the stability sequence: 1-pyrenyl > 4-pyrenyl > 2-pyrenyl in alpha-pyrene-substituted carbocations as models for the intermediates arising from BaP-epoxide ring opening. In an effort to provide a parallel, a series of alpha-pyrenylcarbinols were subjected to a DNA binding study using human MCF-7 cells. The results/trends are discussed and compared with the stable ion data.
Okazaki
Takao
T
Department of Chemistry, Kent State University, Kent, OH 44242, USA.
Laali
Kenneth K
KK
Zajc
Barbara
B
Lakshman
Mahesh K
MK
Kumar
Subodh
S
Baird
William M
WM
Dashwood
Wan-Mohaiza
WM
D000818:Animals; D018383:Bay-Region, Polycyclic Aromatic Hydrocarbon; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives* / Q000378:metabolism*; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism; D002412:Cations; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism; D000432:Methanol / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D002412:Cations; D018736:DNA Adducts; D004852:Epoxy Compounds; D007364:Intercalating Agents; D001564:Benzo(a)pyrene; D004247:DNA; D000432:Methanol