(15N5)-adenine | 77910-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (15N5)-adenine
• 英文别名: Adenine-15N5；7H-purin-6-(15N)amine
• CAS: 77910-29-3
• 化学式: C₅H₅N₅
• 分子量: 140.095
• InChiKey: GFFGJBXGBJISGV-CIKZIQIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (15N5)-adenine 在 溴 作用下， 以 水 为溶剂， 以83%的产率得到(15N5)-8-bromo-adenine
  参考文献：
  名称：

  (¹⁵N₅)-Labeled Adenine Derivatives:  Synthesis and Studies of Tautomerism by ¹⁵N NMR Spectroscopy and Theoretical Calculations

  摘要：

  Since the nitrogens of nucleosides and nucleotides play an important role in the molecular recognition of these compounds, N-15 NMR became a method of choice in this field. Fully N-15-labeled adenine, required in the latter studies, was obtained in four synthetic steps, in a good yield. Likewise, (N-15(5))-2-hexylthioether-adenine and (N-15(5))-8-Br-adenine were obtained in five synthetic steps from the relatively inexpensive N-15 sources: N-15-NH4Cl, N-15-NH4OH, N-15-NaNO2. Full N-15 labeling of these adenine prototypes enabled to obtain high-resolution 15N NMR spectra of these bases at 60.8 MHz. Furthermore, the spectra suggested the existence of the N3-H species in the tautomeric mixtures of these compounds in solution, in addition to the well-reported N9-H (major) and N7-H (minor) tautomers. These observations were also supported by quantum mechanical calculations of the tautomeric equilibria in the gas phase and in solution of the above-mentioned adenine compounds. The gas-phase tautomeric equilibria were estimated using density functional theory and second-order perturbation theory methods. Solvent effects were included by means of both continuum and discrete solvation models. The observation of the existence of the N3-H tautomer has a clear impact on the possible H-bonding patterns of these adenine prototypes and on their molecular recognition by various biological macromolecules. The above(15)N-labeled analogues are expected to find use as N-15 NMR probes for numerous biochemical studies.

  DOI：

  10.1021/jo010344n
• 作为产物：
  描述：

  [15N5]-adenosine triethylamine salt 在 盐酸 作用下， 反应 2.0h， 生成 (15N5)-adenine
  参考文献：
  名称：

  Detection and Quantification of 1,N⁶-Ethenoadenine in Human Placental DNA by Mass Spectrometry

  摘要：

  Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N-6-ethenoadenine (epsilon Ade) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/P-32-postlabeling method. This study reports detection and quantification of the endogenous epsilon Ade adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H. -J. C., et al. (1998) Chem. Res. Toxicol. 11, 1.474], the level of epsilon Ade in human placental DNA from a commercial source was found to be 2.3 adducts per 10(6) Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for epsilon dAdo. With this LC/MS assay, epsilon dAdo was detected at the level of 2.5 adducts per 10(6) dAdo nucleosides in the same human placental DNA. The stable isotopes of epsilon Ade and epsilon dAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of epsilon Ade in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2,3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The epsilon Ade level, in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since epsilon Ade is a potential mutagenic lesion, analysis of epsilon Ade by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.

  DOI：

  10.1021/tx990074s

文献信息

• Molecular Recognition of Adenosine Deaminase:¹⁵N NMR Studies
  作者：Avital Laxer、Hugo E. Gottlieb、Bilha Fischer

  DOI：10.1080/15257770601112713

  日期：2007.3

  The elucidation of the molecular recognition of adenosine deaminase (ADA), the interpretation, of the catalytic mechanism, and the design of novel inhibitors are based mostly on data obtained for the crystalline state of the enzyme. To obtain evidence for molecular recognition of the physiologically relevant soluble enzyme, rue studied its interactions with the in situ formed inhibitor; 6-OH-purine riboside (HDPR), by 1D-N-15- and 2D-(H-1-N-15)- NMR using the labeled primary inhibitor [N-15(4)]-PR. We synthesized both [N-15(4)]-PR and an [N-15(4)]-HDPR model, from relatively inexpensive N-15 sources. The (N-15(4))-HDPR model was used to simulate H-bonding and possible Zn2+-coordination of HDPR with ADA. We also explored possible ionic interactions between PR and ADA by N-15-NMR monitored pH-titrations of (N-15(4))-PR. Finally, we investigaled the [N-15(4)]-PR-ADA 1:1 complex by 2D-(H-1-N-15) NMR. We found that HDPR recognition determinants in ADA do not include any ionic-interactions. HDPR NI H is an H-bond acceptor, and not an H-bond donor: Despite the proximity of N7 to the Zn2+-ion, no coordination occurs; instead, N7 is an H-bond acceptor. We found an overall agreement between the crystallographic data for the crystallized ADA:HDPR complex anal the N-15-NMR signals for the corresponding soluble complex. This finding justifies the use of ADA's crystallographic data for the design of novel inhibitors.
• Detection and Quantification of 1,<i>N</i>⁶-Ethenoadenine in Human Placental DNA by Mass Spectrometry
  作者：Hauh-Jyun Candy Chen、Li-Chang Chiang、Ming-Chung Tseng、Lei L. Zhang、Jinsong Ni、Fung-Lung Chung

  DOI：10.1021/tx990074s

  日期：1999.12.1

  Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N-6-ethenoadenine (epsilon Ade) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/P-32-postlabeling method. This study reports detection and quantification of the endogenous epsilon Ade adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H. -J. C., et al. (1998) Chem. Res. Toxicol. 11, 1.474], the level of epsilon Ade in human placental DNA from a commercial source was found to be 2.3 adducts per 10(6) Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for epsilon dAdo. With this LC/MS assay, epsilon dAdo was detected at the level of 2.5 adducts per 10(6) dAdo nucleosides in the same human placental DNA. The stable isotopes of epsilon Ade and epsilon dAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of epsilon Ade in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2,3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The epsilon Ade level, in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since epsilon Ade is a potential mutagenic lesion, analysis of epsilon Ade by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.
• (¹⁵N₅)-Labeled Adenine Derivatives:  Synthesis and Studies of Tautomerism by ¹⁵N NMR Spectroscopy and Theoretical Calculations
  作者：Avital Laxer、Dan T. Major、Hugo E. Gottlieb、Bilha Fischer

  DOI：10.1021/jo010344n

  日期：2001.8.1

  Since the nitrogens of nucleosides and nucleotides play an important role in the molecular recognition of these compounds, N-15 NMR became a method of choice in this field. Fully N-15-labeled adenine, required in the latter studies, was obtained in four synthetic steps, in a good yield. Likewise, (N-15(5))-2-hexylthioether-adenine and (N-15(5))-8-Br-adenine were obtained in five synthetic steps from the relatively inexpensive N-15 sources: N-15-NH4Cl, N-15-NH4OH, N-15-NaNO2. Full N-15 labeling of these adenine prototypes enabled to obtain high-resolution 15N NMR spectra of these bases at 60.8 MHz. Furthermore, the spectra suggested the existence of the N3-H species in the tautomeric mixtures of these compounds in solution, in addition to the well-reported N9-H (major) and N7-H (minor) tautomers. These observations were also supported by quantum mechanical calculations of the tautomeric equilibria in the gas phase and in solution of the above-mentioned adenine compounds. The gas-phase tautomeric equilibria were estimated using density functional theory and second-order perturbation theory methods. Solvent effects were included by means of both continuum and discrete solvation models. The observation of the existence of the N3-H tautomer has a clear impact on the possible H-bonding patterns of these adenine prototypes and on their molecular recognition by various biological macromolecules. The above(15)N-labeled analogues are expected to find use as N-15 NMR probes for numerous biochemical studies.