稠环芳烃系列化合物化学位移的计算 Ⅱ.甲基稠环芳烃甲基质子化学位移的加合性

本文在稠环芳烃质子化学位移加合性的基础上提出八种类型的结构因素,对11种甲基稠环芳烃的29个非等性甲基质子的化学位移进行了计算.结果表明,甲基稠环芳烃的甲基质子化学位移也相当准确地服从加合性规律.计算值的标准误差为0.12ppm.该计算方法可用于计算稠环芳烃取代基的核磁共振谱。     

1,2-硼氮杂芳烃在中国的研究进展

稠环芳烃及其衍生物在有机光电材料领域具有广泛应用,杂原子掺杂可有效调节稠环芳烃的物理化学性质.用等电子体的硼氮单元取代碳碳单元,在保持稠环芳烃芳香性的连续性的同时,可以调节稠环芳烃的电子结构和分子间相互作用,构建具有独特光电性质和生物活性的新型硼氮杂稠环芳烃,既丰富了稠环芳烃的种类,又促进了硼氮杂芳烃在光电材料、催化和生物医药等领域的应用.近年来,中国有机化学及材料化学领域的学者们积极参与并推动了硼氮杂芳烃的快速发展,在硼氮杂芳烃的种类开发和应用拓展方面开展了一系列原创性的工作,取得了瞩目的成绩.本文综述了基于1,2-硼氮杂苯的稠环芳烃(即1,2-硼氮杂芳烃)的合成发展历史和应用研究拓展,最后对硼氮杂芳烃领域的未来发展与应用进行了展望.通过对硼氮芳烃在中国的发展进行系统的梳理和总结,希望能够引起更多科研工作者对硼氮芳烃的兴趣,期待更多的科研工作者能够加入到硼氮杂芳烃的合成拓展与应用探索中.     

稠环芳烃系列化合物化学位移的计算——Ⅲ.稠环芳烃13C化学位移的加合性

本文在稠环芳烃质子化学位移及甲基稠环芳烃甲基质子化学位移加合性的基础上考虑到稠环芳烃分子中碳原子微环境的特点、π电子环流以及碳原子受到的范德华作用对¹³C化学位移的贡献机理,提出12种类型的六元碳环结构因素,并利用10个化合物的80个¹³C化学位移实验数据得出适合于稠环芳烃¹³C化学位移的普遍公式,按这一公式计算结果的标准误差为lppm,远小于现有的半经验量子力学方法的计算误差.说明稠环芳烃系列分子的¹³C化学位移也存在加合性规律.利用本计算方法可较准确地鉴别和预示已合成的稠环芳烃分子的¹³C化学位移值.本文计算了55个稠环芳烃分子的674个非等性的¹³C化学位移.     

呜拉嗪及其衍生物的合成研究进展

稠环芳烃具有独特的电子性质和光学性质,在有机光电材料领域应用广泛.向稠环芳烃骨架中引入杂原子可改变其电子结构,进而改变其物理、化学、光、电和磁等性质.在众多的杂原子中,氮原子是稠环芳烃中最常见的掺杂原子.呜拉嗪是芘的等电子体,又称吲哚并[6,5,4,3-ija]喹啉,是一种新型氮杂稠环芳烃.近年来,呜拉嗪在染料敏化太阳能电池等领域表现出了潜在应用,随后有关呜拉嗪的合成方法研究备受关注.总结了近年来呜拉嗪及其衍生物的主要合成方法.     

1,4-硼氮杂芳烃在中国的研究进展

稠环芳烃及其衍生物在有机光电材料领域具有广泛应用,杂原子掺杂可有效调节稠环芳烃的物理化学性质.硼氮杂芳烃是稠环芳烃的重要成员.基于硼原子和氮原子的相对位置,硼氮杂芳烃可以分为三种异构体:1,2-硼氮杂芳烃、1,3-硼氮杂芳烃和1,4-硼氮杂芳烃,由于合成上的困难,1,3-硼氮杂芳烃的研究相对较少.近年来,得益于1,4-硼氮杂芳烃在多重共振热活化延迟荧光材料方面潜力的发掘,1,4-硼氮杂芳烃在国内外都取得了飞速发展.我国有机化学及材料化学领域的学者们积极参与并推动了1,4-硼氮杂芳烃的快速发展,在1,4-硼氮杂芳烃的结构开发和应用拓展方面开展了一系列原创性的工作,取得了瞩目的成绩.以1,4-硼氮芳烃的结构作为线索,按照杂原子二元掺杂(B/N)骨架和三元掺杂(X/B/N)骨架分别进行论述,综述了1,4-硼氮杂芳烃的合成发展历史和应用研究拓展,最后对硼氮杂芳烃领域的未来发展与应用进行了展望.     

稠环芳烃在烷基膦酸改性锆镁复合氧化物固定相上的反相液相色谱保留行为

以稠环芳烃为探针 ,考察了烷基膦酸改性锆镁复合氧化物材料的反相色谱性能。研究了稠环芳烃类化合物的结构与其保留值的关系 ,比较了烷基膦酸改性锆镁复合氧化物固定相和十八烷基键合硅胶 Zorbax ODS对稠环芳烃异构体的选择性 ,并对可能的保留机理进行了讨论。以甲醇 -水 (体积比为 75∶ 2 5)为流动相 ,在烷基膦酸改性锆镁复合氧化物固定相上分离了 8种稠环芳烃类化合物     

对稠环烃命名的几点修改建议

基于由纯苯环稠合的稠环芳烃的所有碳原子以sp2杂化不存在额外氢的事实,建议废除对由纯苯环稠合的稠环芳烃额外氢的标明;建议将稠环烃编号从右上方第一个环最上方的自由角开始修改为从右上方第一个环最左方的自由角开始;对文中一些例子命名错误给予了纠正。     

稠环芳烃在烷基膦酸改性锆镁复合氧化物固定相上的反相液相色谱保留行为

 以稠环芳烃为探针,考察了烷基膦酸改性锆镁复合氧化物材料的反相色谱性能。研究了稠环芳烃类化合物的结构与其保留值的关系,比较了烷基膦酸改性锆镁复合氧化物固定相和十八烷基键合硅胶ZorbaxODS对稠环芳烃异构体的选择性,并对可能的保留机理进行了讨论。以甲醇-水(体积比为75∶25)为流动相,在烷基膦酸改性锆镁复合氧化物固定相上分离了8种稠环芳烃类化合物。     

从含有八元环的稠环芳烃到具有负曲率的碳纳米结构:进展与展望

完全由sp²杂化的碳原子所构成的同素异形体呈现出或平坦或弯曲的面,该表面的曲率反映了碳纳米结构的整体几何特性。完全由六元环构成的石墨烯的曲率为零;由六元环和五元环共同构成的富勒烯的曲率为正;向碳原子的六边形网格中引入七元环或八元环则产生形如马鞍的面,其曲率为负。具有负曲率的三维周期性碳结构被命名为马凯晶体或碳施瓦茨体,是碳纳米科学研究长期追寻的目标,然而至今仍未被确定无疑地合成出来。为精确合成具有负曲率的碳纳米结构,一种至下而上的策略是先合成具有负曲率的稠环芳烃,再以其为模板或单体来制备更大的碳纳米结构。具有负曲率的稠环芳烃可以通过向稠环骨架中引入七元或八元环来设计、合成,表现出一些平面稠环芳烃所不具有的结构特征与性质。本文以包含八元环的稠环芳烃为例,介绍具有负曲率的稠环芳烃的设计、合成、立体动力学及其他特征,并展望具有负曲率的碳纳米结构的新研究方向。     

稠环芳烃的化学通式以及其芳香性与休克尔规则的关联

为了阐明稠环芳烃的芳香性, 通过一个简单的数学模型推导出稠环芳烃的分子通式为C4R+2-IH2R+4-I。以此分子通式外推则可以很好地解释为什么任意一个稠环芳烃均符合4n+2的休克尔规则, 并且其中n=R-I/2。利用数学模型得到的这个分子通式提供了一种新的理解芳香性问题的科学思路。     

Multilabeled pyrene-functionalized 2'-amino-LNA probes for nucleic acid detection in homogeneous fluorescence assays

Homogeneous fluorescence assays for detection of nucleic acids are widely used in biological sciences. Typically, probes such as molecular beacons that rely on distance-dependent fluorescence quenching are used for such assays. Less attention has been devoted to tethering a single kind of fluorophores to oligonucleotides and exploiting hybridization-induced modulation of fluorescence intensity for nucleic acid detection. Herein, thermal denaturation experiments and fluorescence properties of oligodeoxyribonucleotides containing one or more 2'-N-(pyren-1-yl)carbonyl-2'-amino-LNA monomer(s) X are described. These pyrene-functionalized 2'-amino-LNAs display large increases in thermal stability against DNA/RNA complements with excellent Watson-Crick mismatch discrimination. Upon duplex formation of appropriately designed 2'-N-(pyren-1-yl)carbonyl-2'-amino-LNA probes and complementary DNA/RNA, intensive fluorescence emission with quantum yields between 0.28 and 0.99 are observed. Quantum yields of such magnitudes are unprecedented among pyrene-labeled oligonucleotides. Molecular modeling studies suggest that the dioxabicyclo[2.2.1]heptane skeleton and amide linkage of monomer X fix the orientation of the pyrene moiety in the minor groove of a nucleic acid duplex. Interactions between pyrene and nucleobases, which typically lead to quenching of fluorescence, are thereby reduced. Duplexes between multiple modified probes and DNA/RNA complements exhibit additive increases in fluorescence intensity, while the fluorescence of single stranded probes becomes increasingly quenched. Up to 69-fold increase in fluorescence intensity (measured at lambda(em) = 383 nm) is observed upon hybridization to DNA/RNA. The emission from duplexes of multiple modified probes and DNA/RNA at concentrations down to less than 500 nM can easily be seen by the naked eye using standard illumination intensities.     

Self-duplex formation of an A(py)-substituted oligodeoxyadenylate and its unique fluorescence

Unexpected homoadenine self-duplexes are formed when pyrene units are bound covalently to the deoxyadenosine bases at specific distances (1,4 relationships). This discovery illustrates how small-molecule pyrene intercalators can be used to drive unknown nucleic acid assembly with a concomitant change in fluorescence. When a pair of pyrene fluorophore units is located within an oligodeoxyadenylate chain, the system can display three different colors (reddish-orange, green, or blue) depending on the relative location of the fluorophores. A unique fluorescence signal, a reddish band peaking at 580 nm, appears when the oligomers possess more than two spacers between the pyrene fluorophores(1,4 relationships). Several spectroscopic experiments, for example, recording variable-concentration spectra, CD, UV, melting temperature, and gel electropherogram, indicate that this new reddish band came from an intermolecular homoadenine self-duplex. Time-resolved fluorescence measurements using both TCSPC and upconversion methods indicate that this unique fluorescence has a long lifetime.     

Fluorescence studies on binding of pyrene and its derivatives to humic acid

Binding of pyrene (PyH) and its derivatives to humic acid (HA) has been studied by fluorescence spectroscopy. The nature of the interaction between HA and pyrene derivatives are extensively investigated by employing three derivatives ranging from anionic to cationic compounds: 1-pyrenebutylic acid (PyA), 1-pyrenemethanol (PyM), and 1-pyrenebutyltrimethylammonium bromide (PyB). Binding constants between HA and PyX (X=H, A, M, B) are obtained by steady-state fluorescence quenching techniques, and it is found that PyB has a markedly large binding constant among the pyrene family. This is attributed to a strong electrostatic interaction between cationic PyB and anionic HA. The result suggests that an electrostatic interaction plays a dominant role in binding of pyrenes to humic acid. The importance of electrostatic interaction was also confirmed by a salt effect on the binding constant. Influence of collisional quenching on the binding constant, which causes overestimation of the binding constant, was examined by time-resolved fluorescence spectroscopy as well as temperature effect in steady-state fluorescence measurements. It is elucidated that collisional quenching does not much bring overestimation into the binding constants.     

Probing solubilization sites in block copolymer micelles using fluorescence quenching

The solubilization sites provided by micelles formed by a diblock copolymer with one neutral hydrophobic block, polystyrene, and one charged hydrophilic block, poly(acrylic acid) or poly(methacrylic acid), have been studied by fluorescence quenching of pyrene by polar and nonpolar quenchers. Pyrene solubilized into these micelles is distributed between the inner corona and the micelle core. The fraction of pyrene residing in the inner corona is almost unity for star micelles, where the corona-forming blocks are larger than the core-forming blocks, and around 0.5 for crew-cut micelles where the opposite situation prevails. The kinetics of the quenching process depends on the pyrene location, i.e. is static in the micelle core, and largely dynamic in the inner corona at low quencher concentration. The rate constants for fluorescence quenching by nitromethane are shown to increase with increasing pH.     

Fluorescence-labelled DNA probes to detect complementary sequences in homogeneous media

Sensitive, safe and easy-to-use probes for the detection of nucleic acids are urgently called for. To this end we are in the process of developing a fluorescence-based technique to work in homogeneous assay media. We have examined pyrene and fluorescein as fluorescent labels for natural DNA probes. A fraction of the cytosine residues of a single-stranded cDNA was randomly labelled with either pyrene or fluorescein using the bisulfite-catalyzed diamine reaction. Both fluorophores showed fluorescence quenching when the labelled probe was hybridized with its complementary strand and we describe the changes in steady-state fluorescence intensity that occurred upon hybridization. Our results demonstrate that pyrene quenching is more efficient than fluorescein quenching and thus pyrene-labelled probes are more sensitive for detecting and quantifying DNA from natural sources.     

Pyrene excimer signaling molecular beacons for probing nucleic acids

Molecular beacon DNA probes, containing 1-4 pyrene monomers on the 5' end and the quencher DABCYL on the 3' end, were engineered and employed for real-time probing of DNA sequences. In the absence of a target sequence, the multiple-pyrene labeled molecular beacons (MBs) assumed a stem-closed conformation resulting in quenching of the pyrene excimer fluorescence. In the presence of target, the beacons switched to a stem-open conformation, which separated the pyrene label from the quencher molecule and generated an excimer emission signal proportional to the target concentration. Steady-state fluorescence assays resulted in a subnanomolar limit of detection in buffer, whereas time-resolved signaling enabled low-nanomolar target detection in cell-growth media. It was found that the excimer emission intensity could be scaled by increasing the number of pyrene monomers conjugated to the 5' terminal. Each additional pyrene monomer resulted in substantial increases in the excimer emission intensities, quantum yields, and excited-state lifetimes of the hybridized MBs. The long fluorescence lifetime ( approximately 40 ns), large Stokes shift (130 nm), and tunable intensity of the excimer make this multiple-pyrene moiety a useful alternative to traditional fluorophore labeling in nucleic acid probes.     

Polyelectrolyte effects on the quenching of pyrene fluorescence in solutions of a pyrene substituted poly(acrylic acid)

The quenching of pyrene fluorescence by nitromethane, Tl⁺, Cu²⁺, I^?, and 4-dimethylaminopyridine (DMAP) in aqueous solutions of a pyrene substituted poly(acrylic acid) ( 1 ) was influenced by the “polyelectrolyte effect” of 1 . The efficiency of quenching in solutions of 1 was measured in terms of the Stern–Volmer constants for dynamic and static quenching which were obtained from comparison of the intensity and lifetime of pyrene fluorescence in solutions of 1 and a monomer model compound. The efficiency of quenching in solutions of 1 was always greater at high pH ( 9 ) in comparison to that at low pH ( 4 ). The ionization of carboxylic groups in 1 caused an expansion of the polymer mainchain and concomitant exposure of the pyrene molecules to the aqueous phase and quencher. The polyanion domain of 1 favored the condensation of cationic quenchers and could account for very efficient quenching in case of Cu²⁺ and Tl⁺. A very efficient quenching of pyrene fluorescence in solutions of 1 by DMAP at high pH was attributed to the hydrophobic interactions of DMAP and pyrene moiety. The iodide ions were less efficient quenchers of pyrene fluorescence due to electrostatic repulsion from the polyanion. The efficiency of quenching by nitromethane was not significantly affected by ionization of the carboxylic groups in 1 .     

FLUORESCENCE STUDY OF THE PHYSICO-CHEMICAL PROPERTIES OF A BENZO(A)PYRENE7,8-DIHYDRODIOL9,10-OXIDE DERIVATIVE BOUND COVALENTLY TO DNA

Abstract— Covalent complexes between 7 ,8-dihydrodiol 9.10-oxide benzo(a)pyrene (BPDE) and DNA with a modification of one BPDE molecule per 1000 DNA bases were prepared in vitro . The same stereoselective and chemically homogeneous binding of BPDE to native DNA was observed, as reported earlier for human and bovine bronchial explants. The fluorescence of the pyrene-like aromatic moiety of BPDE bound to DNA in vitro was used as a probe of the microenvironment of the BPDE molecule in order to obtain information about the structure of the BPDE-DNA complex dissolved in aqueous solution. Fluorescence techniques, based on the quenching of the singlet excited states by metal ions such as Ag⁺, by iodide ions, and by molecular oxygen are described, which provide a method for differentiating between external and internal (intercalation) binding of polycyclic aromatic molecules to DNA. Silver ions, which bind specifically to DNA bases, exhibit a strong quenching effect on noncovalently bound, intercalated benzo(a)pyrene; on the other hand, there is no quenching effect on the fluorescence of BPDE in the covalent DNA adduct. Quenchers such as O₂ and iodide ions, which do not specifically bind to DNA and are dissolved in the solution external to the DNA molecule, exhibit a quenching effect on the BPDE chromophore. Furthermore, the fluorescence yield of the BPDE-DNA complex decreases with increasing DNA concentration, an effect which is not observed with non-covalently bound intercalated benzo(a)pyrene-DNA complexes, and which is attributed to intermolecular DNA-DNA interactions. The results of these studies indicate that the pyrene-like chromophore in the covalent BPDE-DNA complex is not intercalated between the base pairs, and that it is located in an accessible region external to the DNA helix. Possible structures are discussed.     

Stabilization of parallel triplexes by twisted intercalating nucleic acids (TINAs) incorporating 1,2,3-triazole units and prepared by microwave-accelerated click chemistry

A highly efficient method for postsynthetic modification of unprotected oligonucleotides incorporating internal insertions of (R)-1-O-(4-ethynylbenzyl)glycerol has been developed through the application of click chemistry with water-insoluble pyren-1-yl azide and water-soluble benzyl azide and acceleration by microwave irradiation. The twisted intercalating nucleic acids (TINAs) obtained in these reactions, possessing bulged insertions of (R)-3-O-{4-[1-(pyren-1-yl)-1H-1,2,3-triazol-4-yl]benzyl}glycerol (7), formed parallel triplexes with thermal stabilities of 20.0, 34.0, and 40.0 degrees C at pH 7.2 in the cases of one, two, or three insertions of 7, respectively, separated by three nucleic bases. An oligonucleotide with four insertions of 7--each between three nucleic bases in the sequence--was unable to form complexes with complementary single- or double-stranded DNAs, as a result of self-aggregation of the pyrene moieties. This assumption was supported by the formation of a very strong excimer band at 460 nm in the fluorescence spectra. Molecular modeling of the parallel triplex with bulged insertion of the monomer 7 in the triplex-forming oligonucleotide (TFO) showed that only the pyrene moiety was stacking between the bases of the dsDNA, whereas 1,2,3-triazole did not participate in the triplex stabilization. Thermal denaturation studies of the duplexes and triplexes, as well as the fluorescence properties of TINA-triazole 7, are discussed and compared with previous studies on TINA.     

MECHANISMS OF QUENCHING OF THE FLUORESCENCE OF A BENZO[a]PYRENE TETRAOL METABOLITE MODEL COMPOUND BY 2'-DEOXYNUCLEOSIDES

Abstract— The hydrophobic interactions of bulky polycyclic aromatic hydrocarbons with nucleic acid bases and the formation of noncovalent complexes with DNA are important in the expressions of the mutagenic and carcinogenic potentials of this class of compounds. The fluorescence of the polycyclic aromatic residues can be employed as a probe of these interactions. In this work, the interactions of the (+)-trans stereoisomer of the tetraol 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT), a hydrolysis product of a highly mutagenic and carcinogenic diol epoxide derivative of benzo[a]pyrene, were studied with 2′-deoxynucleosides in aqueous solution by fluorescence and UV spectroscopic techniques. Ground-state complexes between BPT and the purine derivatives 2′-deoxyguanosine (dG), 2′-deoxyadenosine (dA), and 2′-deoxyinosine (dI) are formed with association constants in the range of ～40–130 M^?1 Complex formation with the pyrimidine derivatives 2′-deoxythymidine (dT), 2′-deoxycytidine (dC), and 2′-deoxyuridine (dU) is significantly weaker. Whereas dG is a strong quencher of the fluorescence of BPT by both static and dynamic mechanisms (dynamic quenching rate constant k_dyn= [2.5 ± 0.41 × 10⁹M¹ s ¹, which is close to the estimated diffusion-controlled value of ～ 5 × 10⁹M^{? 1} s^?1), both dA and dI are weak quenchers and form fluorescenceemitting complexes with BPT. The pyrimidine derivatives dC, dU, and dT are efficient dynamic fluorescence quenchers (K_dyn～ [1.5–3.0] × 10⁹M^?1 s^?1), with a small static quenching component due to complex formation evident only in the case of dT. None of the four nucleosidcs dG, dA, dC and dT are dynamic quenchers of BPT in the triplet excited state; the observed lower yields of triplets are attributed to the quenching of single excited states of BPT by 2′-deoxynucleosides without passing through the triplet manifold of BPT. Possible fluorescence quenching mechanisms involving photoinduced electron transfer are discussed. The strong quenching of the fluorescence of BPT by dG, dC and dT accounts for the low fluorescence yields of BPT-native DNA and of pyrene-DNA complexes.