Anomeric 5-Aza-7-deaza-2′-deoxyguanosines in Silver-Ion-Mediated Homo and Hybrid Base Pairs: Impact of Mismatch Structure,Helical Environment,and Nucleobase Substituents on DNA Stability

Nucleoside configuration (α-d vs. β-d ), nucleobase substituents, and the helical DNA environment of silver-mediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silver-mediated base pairs of α-d and β-d anomeric 5-aza-7-deaza-2′-deoxyguanosines and anomeric 2′-deoxycytidines incorporated in 12-mer duplexes. To this end, a new synthetic protocol has been developed to access the pure anomers of 5-aza-7-deaza-2′-deoxyguanosine by glycosylation of either the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography. Thermal stability measurements were performed on duplexes with α-d /α-d and β-d /β-d homo base pairs or α-d /β-d and β-d /α-d hybrid pairs within two sequence environments, positions 6 or 7, of oligonucleotide duplexes. The respective T_m stability increases observed after silver ion addition differ significantly. Homo base pairs with β-d /β-d or α-d /α-d nucleoside combinations are more stable than α-d /β-d hybrid base pairs. The positional switch of silver-ion-mediated base pairs has a significant impact on stability. Nucleobase substituents introduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to a minor extent. Our investigation might lead to applications in the construction of bioinspired nanodevices, in DNA diagnostics, or metal-DNA hybrid materials.     

Quantitation of cytidine-5′-monophospho-N-acetylneuraminic acid in human leukocytes using LC–MS/MS: method development and validation

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP-Neu5Ac as well as N-acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography–tandem mass spectrometry methods. A fit-for-purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol–water mixture and the leukocyte extract was used for LC–MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP-Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.     

Straightforward Ball-Milling Access to Dinucleoside 5′,5′-Polyphosphates via Phosphorimidazolide Intermediates

A solvent-assisted mechanochemical approach to access symmetrical and mixed dinucleoside 5,5′-polyphosphates is reported. Under ball-milling conditions, nucleoside 5′-monophosphates were quantitatively activated using 1,1′-carbonyldiimidazole, forming their phosphorimidazolide derivatives. The addition of a nucleoside 5′-mono-, di- or triphosphate directly led to the formation of the corresponding dinucleotides. Benefits of the reported one-pot method include the use of unprotected nucleotides in their sodium or acid form, activation by the eco-friendly 1,1′-carbonyldiimidazole, non-dry conditions, short reaction time, high conversion rates, and easy setup and purification. This work offers new perspectives for the synthesis of nucleotide conjugates and analogues, combining the phosphorimidazolide approach and milling conditions.     

Design of “smart” segmented polymers by incorporating random copolymers as building blocks

This article is dealing with the design of novel segmented polymers comprising homopolymer and random copolymer building blocks designated as block-random. This type of polymeric materials can be prepared through macromolecular engineering by using controlled polymerization methods. By replacing a homopolymer block with a random one, in block copolymer topologies, further tuning of the copolymer properties can be achieved. The present article highlights the recent developments on block-random segmented macromolecules, bearing building blocks of tunable properties (e.g. thermo-sensitivity (LCST), hydrophobicity) and exhibiting responsive behavior in aqueous environments. Furthermore, preliminary novel results regarding pH-sensitive segmented macromolecules of various topologies, bearing random polyampholyte blocks among others, are also demonstrated and discussed.     

Determination of 5-hydroxymethyl-2′-deoxycytidine in Rice by High-performance Liquid Chromatography–Tandem Mass Spectrometry with Isotope Dilution

5-hydroxymethyl-2′-deoxycytidine (5-hmdC), which plays important roles in the epigenetic remodeling in mammals, has been recently determined in plant genomes at trace concentrations. In this study, a method for the sensitive, specific, and rapid assessment of 5-hmdC in rice is reported using high-performance liquid chromatography–tandem mass spectrometry (HPLC–tandem MS) with isotope dilution. The recovery of this method was from 75.6% to 81.3% for 5-hmdC and the intra- and inter-day precision values were within 5.81%. The quantification limit for 5-hmdC was 5.0?pM. Genomic DNA from rice was extracted and enzymatically digested for nucleotides for the HPLC–tandem MS assay. The 5-hmdC levels were 1.32?±?0.08, 1.64?±?0.12, and 1.98?±?0.07 modifications per million nucleosides in the Shengdao-18, Shengxiang-145, and Jindao-263 rice cultivars. The application of HPLC–tandem MS for 5-hmdC demonstrated its presence in the genomic DNA of rice and is useful in further studying the role of modified cytosine in the epigenetic regulation of rice.     

Base catalyzed unexpected rearrangement of isatin-derived N,N′-cyclic azomethine imines and Michael addition to hindered vinylidene bisphosphonates: Access to 3,3-disubstituted oxindole-fused pyrazolidin-3-one derivatives containing bisphosphonates

A new rearrangement of isatin-derived N,N′-cyclic azomethine imines to afford intermediate 3-hydroxy-1H-pyrazole -substituted oxindole was found, and then Michael addition of them to a vinyl bisphosphonate ester provided 3,3-disubstituted oxindole-fused pyrazolidone derivatives containing bisphosphonates in the presence of the readily available DMAP. This transformation is particularly attractive due to features such as unexpected rearrangement, mild conditions, atom economy, the ready availability of the starting materials.     

N,N'-双(4-氯苄基)-1,2-丙二胺合铜(Ⅱ)配合物的合成、晶体结构、抑菌活性及与BSA的相互作用

合成了N,N'-双(4-氯苄基)-1,2-丙二胺铜(Ⅱ)配合物·(NH₄)·Cl₂, 通过元素分析和IR光谱对其进行了表征, 并通过X射线单晶衍射确定了其晶体结构. 晶体结构分析表明, 该晶体属于三斜晶系, P1空间群, 晶胞参数a=1.35222(16) nm, b=1.37899(17) nm, c=1.39806(19) nm; α=60.954(1)°, β=87.502(2)°, γ=65.970(1)°, V=2.0424(4) nm³, D_c=1.357 g/cm³, Z=2, F(000)=862, R₁=0.0925, wR₂=0.2668, S=1.001. 配合物的金属中心与来自2个配体的4个氮原子和1个末端氯原子配位, 形成了轻微扭曲的四方锥几何构型, 扭曲指数τ=0.04(1). 抗菌实验结果显示, 配合物对大肠杆菌、 枯草杆菌和金色葡萄球菌均表现出良好的抑菌作用. 采用荧光光谱研究了不同温度下配合物与牛血清白蛋白(BSA)的相互作用, 结果表明, 配合物对BSA 的荧光猝灭属于静态猝灭. 计算了不同温度下配合物与BSA间的结合常数(K_a), 结合位点(n≈1)及相关热力学参数(ΔH＞0, ΔS＞0, ΔG＜0), 结果表明, 二者主要靠疏水作用力结合. 依据Föster的非辐射能量转移理论, 求得给体(BSA)与受体(配合物)间的距离r=2.56 nm, 说明配合物与BSA 之间可能发生了非辐射能量转移.     

Ruthenium Nanoparticles Loaded on Carbon as Effective Catalyst for Highly Selective Hydrogenation of 4,4′-Methylenedianiline

Supported Ru-based catalysts, prepared by a surfactant-stabilized colloidal method, exhibited a good selectivity to bis(4-aminocyclohexyl)methane via the hydrogenation of 4,4′-methylenedianiline. Transmission electron microscopy(TEM) and X-ray diffraction(XRD) characterization showed Ru nanoparticles were well-dispersed on activated carbon, leading to the high activity and selectivity to the product.     

POLYMERIZATION OF N,N′-(PYROMELLITOYL)-BIS-L-LEUCINE DIACID CHLORIDE WITH HYDANTOIN DERIVATIVES BY MICROWAVE IRRADIATION

Facile and rapid polycondensation reactions of N,N′-(pyromellitoyl)-bis-L-leucine diacid chloride 1 with eight different derivatives of hydantoin compounds 2a-h were developed by using a domestic microwave oven in the presence ora small amount of polar organic medium such as o-cresol. The polycondensation reactions proceeded rapidly, compared with the conventional solution polycondensation, and was completed within 7-10 min, producing a series of novel optically active poly(amide-imide)s 3a-h with high yield and inherent viscosity of 0.35-0.65 dL/g. All of the above polymers were fully characterized by FT-IR, elemental analyses, inherent viscosity (ηiaa), solubility test and specific rotation. Some structural characterization and physical properties of these optically active poly(amide-imide)s are reported.     

利用插值法证明推广的柯西中值定理

借助插值的思想 ,首先给出函数 f( x)的泰勒公式的行列式表达式 ,推广了柯西中值定理 .据此拉格朗日中值定理、泰勒公式、罗必塔法则均是该结论的推论 ,从而对经典的中值定理、泰勒公式、罗必塔法则给出了统一证明