(+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzopyrene | 55097-80-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzopyrene
• 英文别名: (+/-)-trans-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene；(+/-)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene；benzopyrene-trans-7,8-dihydrodiol-9,10-epoxide；(+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene；trans-Anti-benzo(A)pyrene-7,8-diol-9,10-oxide；(6R,7S)-4-oxahexacyclo[11.6.2.02,8.03,5.010,20.017,21]henicosa-1(20),2(8),9,11,13(21),14,16,18-octaene-6,7-diol
• CAS: 55097-80-8；58917-67-2；58917-91-2；60268-85-1；60268-86-2；63323-29-5；63323-30-8；63323-31-9；63357-09-5；64397-28-0；64912-49-8；64912-50-1；82111-22-6
• 化学式: C₂₀H₁₄O₃
• 分子量: 302.329
• InChiKey: DQEPMTIXHXSFOR-WBYGSUFKSA-N

物化性质

• 沸点：
  403.36°C (rough estimate)
• 密度：
  1.1653 (rough estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  53
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

SDS

制备方法与用途

类别：有毒物品

可燃性危险特性：

• 可燃
• 燃烧时产生刺激烟雾

储运特性：

• 通风
• 低温
• 干燥

灭火剂：

• 干粉
• 泡沫
• 沙土
• 二氧化碳
• 雾状水

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzopyrene 在 水 、 sodium cacodylate 、 calf thymus DNA 作用下， 生成 7,8,9,10-四羟基四氢苯并(a)芘
  参考文献：
  名称：

  Photoemission probes of hydrocarbon-DNA interactions: a comparison of DNA influences on the reactivities of (.+-.)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide

  摘要：

  Time-resolved fluorescence and UV photoelectron measurements have been employed to examine the influence of calf thymus DNA on the reactivities of epoxides derived from benzo[a]pyrene (BP) and benz[a]anthracene (BA). By monitoring the increase in fluorescence intensity, which accompanies reaction at 23-degrees-C, overall, pseudo-first-order rate constants have been measured for reactions of the highly carcinogenic bay region epoxide (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and of two less carcinogenic K region epoxides benzo[a]pyrene 4,5-oxide (BPO) and benz[a]anthracene 5,6-oxide (BAO). Overall rate constants for hydrolysis and rearrangement reactions have been measured for BPDE, BPO, and BAO in buffer alone (1.0 mM sodium cacodylate, pH 7.1). The rate constants increase in the order BPO ((3.8 +/- 0.1) x 10(-6) s-1) < BAO ((5.7 +/- 2.6) x 10(-5) s-1) < BPDE ((7.2 +/- 1.0) x 10(-4) s-1). These results have been compared with overall rate constants for reactions, carried out in calf thymus DNA, which result in catalyzed hydrolysis and rearrangement, as well as DNA adduct formation. In DNA, the ordering of the rate constants for BPO and BAO changes from that observed in buffer alone. The rate constants increase in the order BAO ((2.8 +/- 0.1) x 10(-3) s-1) < BPO ((1.2 +/- 0.2) x 10(-2) s-1) < BPDE (approximately 1 x 10(-1) s-1). This ordering is the same as the ordering of association constants for the reversible binding to DNA of the fluorescent diols trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D), trans-4,5-dihydroxy-4,5-dihydro-BP (BP45D) and cis-5,6-dihydroxy-5,6-dihydro-BA (BAD), which are model compounds of BPDE, BPO, and BAO, respectively. For the model compounds, the association constants for intercalation increase in the order BAD ((3.6 +/- 0.9( x 10(2) M-1) < BP45D ((9.6 +/- 0.5) x 10(3) M-1) < BP78D ((3.4 +/- 0.1) x 10(4) M-1). This ordering is consistent with the ordering of the association constants of BPDE ((2.5 +/- 0.3) x 10(4) M-1) and of BPO ((6.0 +/- 1.0) x 10(3) M-1). The temperature dependence of the association constants of the model compounds demonstrates that, for the intercalation of the BP diols into DNA, differences in the enthalpy of binding contribute significantly to differences in the free energy of binding. UV photoelectron data and results from ab initio molecular orbital calculations on BPDE, BPO, and BAO indicate that, for these three epoxides, the association constants increase as the ionization potentials decrease and the polarizabilities increase. The percentage of epoxide reaction that yields DNA adducts has been compared under varying conditions. For long reaction times (> 1 h) in systems containing native, calf thymus DNA at low salt concentrations, the ordering of adduct yields is BPO (14.9 +/- 1.1%) > BPDE (10.1 +/- 3.0%) > BAO (3.6 +/- 0.4%). For short reaction times (10 min) in systems containing native DNA stabilized with 0.10 mM Mg2+, the ordering of adduct yields is BPDE (7.3 +/- 1.9%) > BPO (1.3 +/- 0.1%) > BAO (0.1 +/- 0.1%). These results suggest that the ability of an epoxide to form adducts with exposed DNA during long reaction times is less indicative of the genotoxic potency of the epoxide than its ability to form adducts with stabilized DNA during short reaction times.

  DOI：

  10.1021/ja00010a033
• 作为产物：
  描述：

  7,8-二羟基-7,8-二氢-苯并(a)芘 、 间氯过氧苯甲酸 以56%的产率得到
  参考文献：
  名称：

  MCCAUSTLAND D. J.; ENGEL J. F., TETRAHEDRON LETT. , 1975, NO 30, 2549-2552

  摘要：

  DOI：

文献信息

• Method for the Rapid Detection and Molecular Characterization of DNA Alkylating Agents by MALDI-TOF Mass Spectrometry
  作者：Ignazio Garaguso、Roman Halter、Jacek Krzeminski、Shantu Amin、Jürgen Borlak

  DOI：10.1021/ac101568h

  日期：2010.10.15

  Metabolic activation of polycyclic aromatic hydrocarbons (PAH) may cause DNA adduct formation. While these are commonly detected by the 32P-postlabeling assay, this method is not informative on the chemical nature of the alkylating agent. Here we report a simple and reliable method that employs MALDI-TOF-MS with 2,5-dihydroxybenzoic acid (DHB) matrix layer (ML) sample preparations for the detection and structural characterization of PAH-DNA adducts. The method involves the enzymatic digestion of DNA to 2′-deoxynucleotides followed by solid phase extraction to remove salt and other contaminants prior to MALDI-MS analysis. By collision induced dissociation (CID) structurally relevant fragments are obtained to permit characterization of the alkylating molecules and the adducted nucleotide. Next to guanosine, adenosine and cytidine adducts formed from reactions with (±)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE) are identified at a sensitivity of <100 fmol and a mass accuracy of <10 ppm. Studies with (±)-anti-benzo[c]chrysene-9,10-diol-11,12-epoxide (B[c]ChDE) further document the versatility and usefulness of the method. When compared with the 32P-postlabeling assay MALDI-MS only indentified deoxycytidine as well nucleoside and dinucleotides adducts. Therefore, this sensitive method enables molecular specification and characterization of adducted nucleotides and of the alkylating agent, and thus, provides comprehensive information that is beyond the 32P-postlabeling assay.

  多环芳烃（PAH）的代谢活化可能会导致DNA加合物形成。虽然这些通常可以通过32P后标记检测法检测到，但这种方法并不能提供烷基化剂的化学性质信息。在此，我们报告了一种简单可靠的方法，该方法利用MALDI-TOF-MS与2,5-二羟基苯甲酸（DHB）基质层（ML）样品制备，用于检测和结构表征PAH-DNA加合物。该方法包括将DNA酶解为2′-脱氧核苷酸，然后进行固相萃取以去除盐和其他污染物，再进行MALDI-MS分析。通过碰撞诱导解离（CID），获得结构相关的片段，从而表征烷基化分子和加合的核苷酸。与鸟苷类似，与（±）-反式苯并[a]芘-7,8-二醇-9,10-环氧化物（B[a]PDE）反应形成的腺苷和胞苷加合物，其识别灵敏度小于100 fmol，质量精度小于10 ppm。与（±）-反式苯并[c]屈-9,10-二醇-11,12-环氧化物（B[c]ChDE）的研究进一步证明了该方法的多功能性和实用性。与32P
• Photoemission probes of catalysis of benzo[a]pyrene epoxide reactions in complexes with linear, double-stranded and closed-circular, single-stranded DNA
  作者：Chao Ran Huang、Ann Milliman、Harry L. Price、Shigeyuki Urano、Sharon M. Fetzer、Pierre R. LeBreton

  DOI：10.1021/ja00070a028

  日期：1993.8

  Fluorescence intensity measurements of overall, pseudo-first-order rate constants for two epoxide-containing metabolites of benzo[a]pyrene (BP) were carried out in Tris, EDTA buffer (pH 7.3) without DNA, and in buffer with double-stranded calf thymus DNA (DS ctDNA) and with closed-circular, single-stranded viral M13mp19 DNA (SS M13 DNA). Highly purified SS M13 DNA was employed in order to avoid polymeric contamination which is present in DNA samples obtained using a standard preparation method relying on phenol extraction and which influences results from measurements of DNA-ligand interactions. The BP metabolites examined were highly carcinogenic (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and less genotoxic benzo[a]pyrene 4,5-oxide (BPO). Without DNA, BPDE hydrolyzes to 7,8,9,10-tetrahydroxytetrahydro-BP, while BPO hydrolyzes to trans-4,5-dihydroxy-4,5-dihydro-BP(BP45D) and rearranges to 4-hydroxy-BP. With DNA, BPDE and BPO hydrolysis and rearrangement are catalyzed, and DNA modification occurs. In DS ctDNA, previous kinetic and binding measurements indicate that catalysis occurs primarily at intercalation sites. In SS M13 DNA (0.20 mM), BPDE has overall, pseudo-first-order rate constants (k) of (12 +/- 1) X 10(-3) and (2.8 +/- 0.5) X 10(-3) s-1, at Na+ concentrations of 2.0 and 100 mM, respectively. At these Na+ concentrations, values of k measured in SS M13 DNA are 3-16 times larger than values measured without DNA, but smaller than values measured in DS ctDNA. For BPO, the ordering of k values without DNA, with SS M13 DNA, and with DS ctDNA is the same as for BPDE. At 2.0 mM Na+, the nonreactive diols, trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D) and BP45D, which are model compounds for BPDE and BPO, respectively, have SS M13 DNA association constants [(7.2 +/- 0.5) X 103 and (2.7 +/- 0.5) X 10(3) M-1] that are 2.3 times smaller than DS ctDNA association constants. In contrast, at 100 mM Na+, association constants for SS M13 DNA are 2.9-3.1 times larger than for DS ctDNA. Fluorescence lifetime measurements indicate that, in SS M13 DNA, reversible binding involves intercalation into local duplex regions. Estimated catalytic rate constants (k(cat)) for BPDE hydrolysis in SS M13 DNA, obtained from BP78D association constants and from k values measured with and without DNA, are (22.8 +/- 2.5) X 10(-3) and (3.5 +/- 0.7) X 10(-3) s-1, at 2.0 and 100 mM Na+, respectively. For this Na+ concentration range, the ratio of k(cat) values for DS ctDNA versus SS M13 DNA is almost constant (1.7 +/- 0.6) even though the absolute k(cat) values vary by more than a factor of 5. The similar magnitudes of k(cat) values for SS M13 DNA and DS ctDNA provide evidence that catalytic sites in SS M13 DNA are similar to intercalated catalytic sites in DS ctDNA.
• Photoemission probes of hydrocarbon-DNA interactions: a comparison of DNA influences on the reactivities of (.+-.)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide
  作者：Shigeyuki Urano、Harry L. Price、Sharon M. Fetzer、Anita V. Briedis、Ann Milliman、Pierre R. LeBreton

  DOI：10.1021/ja00010a033

  日期：1991.5

  Time-resolved fluorescence and UV photoelectron measurements have been employed to examine the influence of calf thymus DNA on the reactivities of epoxides derived from benzo[a]pyrene (BP) and benz[a]anthracene (BA). By monitoring the increase in fluorescence intensity, which accompanies reaction at 23-degrees-C, overall, pseudo-first-order rate constants have been measured for reactions of the highly carcinogenic bay region epoxide (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and of two less carcinogenic K region epoxides benzo[a]pyrene 4,5-oxide (BPO) and benz[a]anthracene 5,6-oxide (BAO). Overall rate constants for hydrolysis and rearrangement reactions have been measured for BPDE, BPO, and BAO in buffer alone (1.0 mM sodium cacodylate, pH 7.1). The rate constants increase in the order BPO ((3.8 +/- 0.1) x 10(-6) s-1) < BAO ((5.7 +/- 2.6) x 10(-5) s-1) < BPDE ((7.2 +/- 1.0) x 10(-4) s-1). These results have been compared with overall rate constants for reactions, carried out in calf thymus DNA, which result in catalyzed hydrolysis and rearrangement, as well as DNA adduct formation. In DNA, the ordering of the rate constants for BPO and BAO changes from that observed in buffer alone. The rate constants increase in the order BAO ((2.8 +/- 0.1) x 10(-3) s-1) < BPO ((1.2 +/- 0.2) x 10(-2) s-1) < BPDE (approximately 1 x 10(-1) s-1). This ordering is the same as the ordering of association constants for the reversible binding to DNA of the fluorescent diols trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D), trans-4,5-dihydroxy-4,5-dihydro-BP (BP45D) and cis-5,6-dihydroxy-5,6-dihydro-BA (BAD), which are model compounds of BPDE, BPO, and BAO, respectively. For the model compounds, the association constants for intercalation increase in the order BAD ((3.6 +/- 0.9( x 10(2) M-1) < BP45D ((9.6 +/- 0.5) x 10(3) M-1) < BP78D ((3.4 +/- 0.1) x 10(4) M-1). This ordering is consistent with the ordering of the association constants of BPDE ((2.5 +/- 0.3) x 10(4) M-1) and of BPO ((6.0 +/- 1.0) x 10(3) M-1). The temperature dependence of the association constants of the model compounds demonstrates that, for the intercalation of the BP diols into DNA, differences in the enthalpy of binding contribute significantly to differences in the free energy of binding. UV photoelectron data and results from ab initio molecular orbital calculations on BPDE, BPO, and BAO indicate that, for these three epoxides, the association constants increase as the ionization potentials decrease and the polarizabilities increase. The percentage of epoxide reaction that yields DNA adducts has been compared under varying conditions. For long reaction times (> 1 h) in systems containing native, calf thymus DNA at low salt concentrations, the ordering of adduct yields is BPO (14.9 +/- 1.1%) > BPDE (10.1 +/- 3.0%) > BAO (3.6 +/- 0.4%). For short reaction times (10 min) in systems containing native DNA stabilized with 0.10 mM Mg2+, the ordering of adduct yields is BPDE (7.3 +/- 1.9%) > BPO (1.3 +/- 0.1%) > BAO (0.1 +/- 0.1%). These results suggest that the ability of an epoxide to form adducts with exposed DNA during long reaction times is less indicative of the genotoxic potency of the epoxide than its ability to form adducts with stabilized DNA during short reaction times.
• MCCAUSTLAND D. J.; ENGEL J. F., TETRAHEDRON LETT. <TELE-AY>, 1975, NO 30, 2549-2552
  作者：MCCAUSTLAND D. J.、 ENGEL J. F.

  DOI：——

  日期：——