Synthesis of 8-(omega-Hydroxyalkyl)-, 8-(omega-hydroxyalk-1-enyl)-, and 8-(omega-hydroxyalk-1-ynyl)adenines using the tert-butyldimethylsilyloxymethyl group, a new and versatile protecting group of adenine

The synthesis of 12 analogues of adenine substituted at C-8 by an omega-hydroxyalkyl, omega-hydroxyalk-1-enyl, or omega-hydroxyalk-1-ynyl chain of various length has been carried out in five or six steps starting from adenine. The analogues were obtained using a new protecting group of adenine, the tert-butyldimethylsilyloxymethyl group. 9-tert-Butyldimethylsilyloxymethyl-adenine is more soluble than adenine in organic solvents. It was prepared regiospecificaly in two steps from adenine and was amenable to C-8 iodination under basic conditions and to subsequent introduction of the various carbon chains at C-8 by palladium-catalyzed cross-coupling reactions (Stille or Sonogashira). The protecting group was removed under acidic conditions, thus demonstrating its versatility.     

基于BCNTs/GC电极的鸟嘌呤与腺嘌呤电化学行为及其同时检测

利用掺硼碳纳米管（BCNTs）/GC电极研究了鸟嘌呤（G）和腺嘌呤（A）的电化学氧化行为. 与GC和CNTs/GC电极相比,BCNTs/GC电极具有更强的电催化活性,且响应电流明显增加. 两混合样品在BCNTs/GC电极上的氧化峰间隔较大,可实现对A和G的同时检测.     

Novel electrochemical sensor based on functionalized graphene for simultaneous determination of adenine and guanine in DNA

A nano-material carboxylic acid functionalized graphene (graphene-COOH) was prepared and used to construct a novel biosensor for the simultaneous detection of adenine and guanine. The direct electrooxidation behaviors of adenine and guanine on the graphene-COOH modified glassy carbon electrode (graphene-COOH/GCE) were carefully investigated by cyclic voltammetry and differential pulse voltammetry. The results indicated that both adenine and guanine showed the increase of the oxidation peak currents with the negative shift of the oxidation peak potentials in contrast to that on the bare glassy carbon electrode. The electrochemical parameters of adenine and guanine on the graphene-COOH/GCE were calculated and a simple and reliable electroanalytical method was developed for the detection of adenine and guanine, respectively. The modified electrode exhibited good behaviors in the simultaneous detection of adenine and guanine with the peak separation as 0.334V. The detection limit for individual determination of guanine and adenine was 5.0×10(-8)M and 2.5×10(-8)M (S/N=3), respectively. Furthermore, the measurements of thermally denatured single-stranded DNA were carried out and the value of (G+C)/(A+T) of single-stranded DNA was calculated as 0.80. The biosensor exhibited some advantages, such as simplicity, rapidity, high sensitivity, good reproducibility and long-term stability.     

Controlled aggregation of adenine by sugars: physicochemical studies, molecular modelling simulations of sugar-aromatic CH-pi stacking interactions, and biological significance

CH-Pi stacking interactions between carbohydrates and aromatic compounds play a central role in biomolecular recognition, especially in lectin-sugar and protein-glycolipid systems. In the present study, we have measured the solubility of the sparingly soluble aromatic base adenine in presence of various saccharides as an approach to investigate the interaction between adenine and sugars. Above 82.5 mM, adenine solutions gradually formed a crystalline precipitate which could be quantified by spectrophotometric turbidity measurements. Precipitation of adenine was increased by salts (NaCl and NaF) whereas it was prevented by DMSO, in agreement with the involvement of hydrophobic interactions (pi-pi stacking) in the vertical stacking of adenine molecules. Several monosaccharides and disaccharides were found to increase adenine solubility, with the following order: D-galactose = D-lactose > D-sucrose > D-glucose = D-maltose > D-ribose > D-fructose. Molecular mechanics simulations indicated that the potent cosolvent effect of beta-D-galactopyranose was probably mediated by CH-pi stacking interactions between its apolar surface and the aromatic structure of adenine. The polar OH groups of the sugars interacted with surrounding water molecules, ensuring the solubility of sugar-adenine complexes. In contrast, beta-D-fructofuranose, which has two polar faces, did not stack onto adenine and had a weak cosolvent effect. CH-pi stacking interactions were also demonstrated between 6-methylpurine and the sugar head group of glycolipids (glucosyl-, galactosyl- and lactosylceramide) but not with the charged head group of phosphatidylinositol-4,5-diphosphate. These data indicate that galactose-containing molecules have a high stacking propensity for aromatic compounds such as adenine, due to the specific structure of the galactose cycle.     

π堆积的腺嘌呤-胸腺嘧啶体系激发态电荷转移和无辐射失活的半经典动力学模拟

采用半经典电子-辐射-离子动力学(SERID)模型模拟了π堆积的腺嘌呤-胸腺嘧啶(A-T)体系激发态的光物理失活过程. 设置激光脉冲仅作用于T, 模拟发现电子由A转移到T, 形成(A⁺T^-)^*激基缔合物(exciplex). 当分子间距缩短至0.300 nm时, 由于轨道离域效应产生电荷重组, 体系恢复电中性; 当A分子的C4'－C5'扭曲程度最大时, 体系通过避免交叉点衰减至基态. Exciplex 的失活途径由分子间距离和A分子的变形程序两个因素决定. 由于A分子的C4'、C5'原子位阻较大, 难以达到失活所必需的强烈扭曲, 因此(A-T)^*的寿命比胸腺嘧啶堆积体系(T-T)^*显著增长.     

腺嘌呤电化学氧化及反应速度常数测定

腺嘌吟(6-氨基嘌呤)的初级电解氧化过程即由化合物Ⅰ氧化至化合物Ⅱ是一个多步的、高度不可逆的六电子转移过程已为周期伏安法(简称CV实验所证实,其限速步骤电子转移数n_b=2^[1],在线性扩散条件下,完全不可逆电极过程CV氧化峰电位时的异相反应速度常数为^[2]。     

Voltammetric Characteristics of Adenine and Adenosine at a Copper Electrode and Their Application to End-Column Amperometric Detection for Capillary Zone Electrophoresis

Abstract

The voltammetric characteristics of adenine and adenosine at a copper electrode were investigated in different supporting electrolytes. It was found that citric acid had some activating effect at the copper electrode and the oxidation reaction of adenine and adenosine at the copper electrode could be observed in the solution, if PO₄ ^3? and citric acid exist simultaneously. The oxidation reaction of adenine and adenosine could be applied to capillary zone electrophoresis with end column amperometric detection for their determination. The method was applied to the determination of adenine in yeast-RNA.     

Synthesis of adenine derivatives containing an amino alcohol fragment

The alkylation of adenine and N(in6)-substituted adenine derivatives by 1, 2-dihaloethanes and the production of 9-(2-haloethyl)derivatives of adenine were studied. 1n the reaction of the derivatives with amino alcohols a series of adenine derivatives containing an amino alcohol fragment was synthesized.Latvian Institute of Organic Synthesis, Riga, LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 386–390, March, 1996. Original article submitted March 7, 1995.     

Functional monomers and polymers. XCIV. Photochemical reactions on the synthetic polymers containing thymine bases in the presence of adenine derivatives

Photodimerization reactions of polyacrylate and polymethacrylate derivatives and the dimer model compound containing thymine bases were studied in the presence of adenine derivatives in dimethyl sulfoxide; N,N-dimethylformamide; and dimethyl sulfoxide–ethylene glycol solutions. The photodimerization of thymine bases both in the polymers and in the dimer model compound was found to be quenched by the addition of adenine derivatives. Base-base interaction in the ground state was also studied by ultraviolet (UV) spectroscopy in the three solvents. The quenching of the photodimerizationof thymine bases in the presence of adenine derivatives was discussed in terms of the specific interaction between adenine and thymine bases both in ground and excited states.     

腺嘌呤与富马酸共晶体的太赫兹光谱分析

利用太赫兹时域光谱(THz-TDS)技术在室温下对腺嘌呤、富马酸及两者的共晶体进行测量, 实验结果显示腺嘌呤与富马酸共晶体在0.92、1.24、1.52 THz处有明显的吸收峰, 与腺嘌呤和富马酸不同, 表明共晶体物相结构不同于原料. 根据腺嘌呤分子氢键供体与受体的结构特点, 使用密度泛函理论(DFT)对腺嘌呤与富马酸三种可能的共晶体结构进行模拟. 结果显示其中一种可能的共晶体结构在0.89、1.16、1.41 THz处存在特征吸收峰, 与实验结果较好吻合. 由此判断腺嘌呤与富马酸共晶体氢键形成位置为腺嘌呤的氨基与富马酸其中一个羧酸的碳氧双键形成氢键, 而此羧酸的羟基与腺嘌呤六元环上的邻位氮原子形成第二处氢键. 本文还结合理论模拟的结果对腺嘌呤与富马酸共晶体的特征吸收峰对应的相关振动模式进行了归属.     

Fabrication of Cu−CeO2 Coated Multiwall Carbon Nanotube Composite Electrode for Simultaneous Determination of Guanine and Adenine

A copper nano particles and cerium (IV) oxide modified carbon nanotube based composite on glassy carbon electrode (Cu−CeO₂/MWCNT/GCE) was fabricated for simultaneous determination of guanine and adenine. The surface morphology, chemistry and conductance of the prepared electrodes were characterized by scanning electron microscopy (SEM), energy dispersion X‐ray (EDX), X‐Ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). The Cu−CeO₂/MWCNT/GCE improved electrochemical behaviour of guanine and adenine compared to other electrodes. The modified electrode was also used for individual and simultaneous determination of guanine and adenine. Under optimized conditions, the calibration curves were obtained linearly in the range of 0.20 to 6.00 μM for the guanine and 0.10 to 8.0 μM for the adenine by differential pulse voltammetry. The limits of detection of guanine and adenine were calculated as 0.128 and 0.062 μM, respectively. Interferences studies were also performed in the presence of inorganic and organic compounds. Moreover, the determination of guanine and adenine contents were carried out in a calf thymus DNA sample by the developed method with satisfactory results.     

碱基腺嘌呤与多肽酰胺间氢键作用的最佳位点

正确理解核酸碱基和蛋白质多肽间的作用机制有助于人们利用这些生物分子有效地进行分子设计,进而制备具有特殊纳米结构和功能的生物分子材料.本文优化得到了碱基腺嘌呤与N-甲基乙酰胺、甘氨酸二肽、丙氨酸二肽形成的20个氢键复合物的结构并计算了结合能,探讨了腺嘌呤与多肽酰胺间氢键作用的最佳位点.研究发现:腺嘌呤可以使用两个不同位点(A1位点和A2位点)与N-甲基乙酰胺形成N―H…N型或者N―H…O=C型氢键复合物,腺嘌呤使用A1位点与N-甲基乙酰胺形成的N―H…N型氢键复合物更稳定;二肽分子可以使用主链上两个不同位点(丙氨酸的Ala7位点和Ala5位点或者甘氨酸的Gly7位点和Gly5位点)与腺嘌呤形成含有N―H…N和N―H…O=C两条氢键的复合物,二肽分子使用Ala7或Gly7位点与腺嘌呤形成的氢键复合物更稳定;腺嘌呤与多肽间的氢键作用强于其与N-甲基乙酰胺的作用.基于分子中的原子理论与自然键轨道计算结果分析了氢键作用的本质.     

Eigenvector mapping: a method for discerning solvent effects on vibrational spectra

This paper reports a density functional theory (DFT) analysis of the adenine spectra in a hydrogen-bonding environment. We compare the theoretical vibrational spectra of 26 model systems in which water has been hydrogen bonded to adenine with the experimental frequencies of the solid state infrared spectra (150-1700 cm(-1)) of polycrystalline adenine and the experimental frequencies observed in matrix isolation spectra of adenine [J. Phys. Chem. 100 (1996) 3527]. The vibrational eigenvectors of adenine are compared by taking the dot product to determine how the normal modes of the 15-adenine atoms are affected by different hydrogen bonding geometries. Using the isolated adenine molecule as a reference permits a comparison of different calculated spectra in terms of the projections of various normal modes and the determination of the potential energy redistribution among normal modes. This method creates a map of the normal modes using the isolated adenine molecule as a reference. Improvement in agreement between the polycrystalline data and a model of adenine with four waters is most striking. The improvement in the fit between matrix isolation data and a model of adenine with a single water was not as dramatic as the fit seen for the polycrystalline data, but the fact that a single hydrogen-bonded water shifted the spectra of the model to a closer fit than that of isolated adenine is important. We call this method eigenvector mapping. The eigenvector mapping method can be used to extract the normal modes of a parent molecule from a solvent model system. The application of this method is important because it aids in the interpretation of complex molecular interactions in terms of the spectrum of an isolated molecule. The eigenvector mapping procedure will be shown to greatly improve the correspondence between the model and the experimental data.     

Fabrication of poly(2,6-pyridinedicarboxylic acid)/MWNTs modified electrode for simultaneous determination of guanine and adenine in DNA

The fabrication of poly(2,6-pyridinedicarboxylic acid)/MWNTs modified glass electrode(PPDA/MWNTs/GCE) was proposed and used for individual or simultaneous determination of guanine and adenine.The performances of the PPDA/MWNTs/GCE were characterized with cyclic voltammetry(CV).The modified electrode exhibited enhanced electrocatalytic behavior and good stability for the detection of guanine and adenine.Differential pulse voltammetry(DPV) was used to determine the concentration of guanine,adenine.The detection limit(S/N = 3) for guanine and adenine was 0.045μmol/L and 0.05μmol/L,respectively.The electrochemical method for the measurement of guanine and adenine in calf thymus DNA was also developed with this modified electrode and the result was satisfactory.     

腺嘌呤和质子化腺嘌呤的结构和振动光谱

用密度泛函方法B3LYP/aug-cc-pVTZ分析了腺嘌呤和质子化腺嘌呤的低能稳定异构体的结构和振动光谱. 结果发现, 对于中性腺嘌呤分子, 腺嘌呤的异构体N9H比N7H的能量低32.76 kJ·mol-1(在极化连续模型下为6.28 kJ·mol-1). 基于标度量子力场方法所得到的势能分布, 对异构体N9H的部分振动基频重新进行了归属. 在极化连续模型下, 质子化腺嘌呤分子有5种低能稳定构型, 其中N1位质子化的9-位氢腺嘌呤最为稳定. 基于振动模式分析, 对这种最稳定构型的振动基频进行了归属, 并对腺嘌呤在pH=1的高氯酸溶液中的实验拉曼光谱进行了指认.     

Adenine radicals in the gas phase: an experimental and computational study of hydrogen atom adducts to adenine

The elusive hydrogen atom adduct to the N-1 position in adenine, which is thought to be the initial intermediate of chemical damage, was specifically generated in the gas phase and characterized by neutralization-reionization mass spectrometry. The N-1 adduct, 1,2-dihydroaden-2-yl radical (1), was generated by femtosecond electron transfer to N-1-protonated adenine that was selectively produced by electrospray ionization of adenine in aqueous-methanol solution. Radical 1 is an intrinsically stable species in the gas phase that undergoes specific loss of the N-1-hydrogen atom to form adenine, but does not isomerize to the more stable C-2 adduct, 1,2-dihydroaden-1-yl radical (5). Radicals 1 that are formed in the fifth and higher electronically excited states of DeltaE > or = 2.5 eV can also undergo ring-cleavage dissociations resulting in expulsion of HCN. The relative stabilities, dissociation, and transition state energies for several hydrogen atom adducts to adenine have been established computationally at highly correlated levels of theory. Transition state theory calculations of 298 K rate constants in the gas phase, including quantum tunnel corrections, indicate the branching ratios for H-atom additions to C-8, C-2, N-3, N-1, and N-7 positions in adenine as 0.68, 0.20, 0.08, 0.03, and 0.01, respectively. The relative free energies of adenine radicals in aqueous solution point to the C-8 adduct as the most stable tautomer, which is predicted to be the predominating (>99.9%) product at thermal equilibrium in solution at 298 K.     

Measurement of adenine nucleotide levels with an adenine analyser as an index of freshness of porgy

In a prototype of an adenine analyser, adenosine and adenine nucleotides were derivatized with a fluorescent reagent, bromoacetaldehyde, after separation on a Hitachi gel No. 3012-N column by high-performance liquid chromatography. The previous analyser was improved by using a shorter reaction coil and by introduction of a Hitachi gel No. 3013-N with 5-microns particles of porous polystyrene-divinylbenzene, and applied to estimate the freshness of porgy. Total amounts of ATP, ADP and AMP in an isolated muscle just after death gradually decreased to 60% of the original amount after 5 h, and the ATP content rapidly decreased to 20% after 1 h. A good correlation was found between the levels of total adenine compounds and the energy charge values obtained from nineteen porgies frozen at a prerigour state. On the other hand, there existed no relationship between total adenine levels and the K values, which were indices for estimating freshness of fish. The analyser will be useful to evaluate the freshness of tissues and cells based on the higher contents of total adenine compounds, especially ATP.     

Intrinsic acidity and redox properties of the adenine radical cation

The intrinsic chemical properties of the gaseous adenine radical cation were examined by using dual cell Fourier transform ion cyclotron resonance mass spectrometry. The adiabatic recombination energy of the radical cation (ionization energy of neutral adenine) was found by bracketing experiments to be 8.55 ± 0.1 eV (at 298 K; earlier literature values range from 8.3 to 8.9 eV). Based on this value, the heat of formation (ΔH_f²⁹⁸) of the adenine radical cation is estimated to be 246 ± 3 kcal/mol. The acidity (ΔH_acid²⁹⁸) of the adenine radical cation was bracketed to be 221 ± 2 kcal/mol. These thermochemical values suggest that the adenine radical cation reacts with neutral guanine by electron abstraction or proton transfer, with neutral cytosine by proton transfer, and via neither pathway with neutral thymine, molecular water or a sugar moiety of DNA (modeled by tetrahydrofuran). Experimental examination of the gas-phase reactivity of the adenine radical cation revealed a slow deuterium atom abstraction from perdeuterated tetrahydrofuran. Hence, in the absence of a nearby guanine or cytosine, the adenine radical cation may be able to abstract a hydrogen atom from a sugar moiety of DNA.     

Copolymers containing alternating sequences of nucleic acid base pairs. II. Polymerization studies

The objective of this project was to utilize the alternating copolymerizability of electrondonor monomers with electron-acceptor monomers to selectively introduce nucleic acid bases into copolymers in a controlled sequence distribution. To this end, maleimide monomers containing the adenine, thymine, cytosine, and 6-chloropurine moieties were converted to their hompolymers. The homopolymer of 1-(vinyloxyethoxy)thymine was also prepared. Alternating copolymers of the adenine maleimide monomer and the corresponding 6-chloropurine maleimide monomer with 1-(vinyloxyethoxy)thymine were prepared. The latter copolymer was converted to the alternating adenine–thymine copolymer by reaction with ammonia. Characterization of the polymers and copolymers via spectroscopic methods and physical measurements confirm their proposed structures. Monomer syntheses and characterization, as well as studies designed to establish the extent and nature of adenine–thymine interactions in the copolymers, are reported in accompanying papers.     

Bis-phenanthridinium–adenine conjugates as fluorescent and CD reporters for fine structural differences in ds-DNA/RNA and ss-RNA structures

Two structurally similar bis-phenanthridinium–adenine conjugates (equipped with one or two adenines, respectively), exhibiting strong ds-DNA/RNA groove binding, revealed ratiometric fluorescent recognition of alternating AT-DNA with respect to other ds-DNA/RNA and ss-RNA. Further, CD spectra pattern of adenine–bis-phenanthridinium conjugate/polynucleotide complexes strongly depended on polynucleotide secondary structure. Attached adenine was essential for spectrophotometric recognition response, ds-DNA stabilisation and orientation of compounds regarding chiral DNA helix.