铂配位的腺嘌呤质子化的理论研究

用量子化学从头算研究一系列平面四方金属配体作用于腺嘌呤N₇位点对其质子化的影响。计算结果表明气相中，配合物质子化能力主要受长程静电效应影响，不同金属离子的影响差别甚微。综合考虑极性溶剂影响后长程静电效应影响显著降低。NBO电荷布居分析表明质子化位点电子云密度的变化直接影响该位点质子化能力。     

紫外线激活氚原子—制备氚标记单磷酸阿糖腺苷的研究

本文采用紫外线激活氚原子的方法,进行氚-氢同位素交换反应,制得氚标记单磷酸阿糖腺苷(9—~3H—mparaA)。产品的纯度是层析纯;放射性比活度16GBq.m mol~(-1);放射化学纯度92.0%。本法的优点是:交换反应温和、反应时间较短、不易破坏生物活性、引起的副产物少、产品分离和纯化较方便。     

A general approach toward the synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines

An expedient synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines was developed by treating 8-amino-4-[N-(4-aminophenyl)-N-(methyl)amino]pyrazolo[1,5-a]-1,3,5-triazine with various acyl chlorides following by the displacement of the so-formed N-(methyl)-N-[4-(acylamido)phenyl]amino leaving group with various amines. Applications to high-throughput synthesis are suggested.     

Onset of Chiral Adenine Surface Growth

The structure and stability of adenine crystals and thin layers has been studied by using scanning tunneling microscopy, X‐ray diffraction, and density functional theory calculations. We have found that adenine crystals can be grown in two phases that are energetically quasi‐degenerate, the structure of which can be described as a pile‐up of 2D adenine planes. In each plane, the structure can be described as an aggregation of adenine dimers. Under certain conditions, kinetic effects can favor the growth of the less stable phase. These results have been used to understand the growth of adenine thin films on gold under ultra‐high vacuum conditions. We have found that the grown phase corresponds to the α‐phase, which is composed of stacked prochiral planes. In this way, the adenine nanocrystals exhibit a surface that is enantiopure. These results could open new insight into the applications of adenine in biological, medical, and enantioselective or pharmaceutical fields.     

烟酰胺腺嘌呤二核苷酸磷酸与纳米氧化铝和勃姆石的作用

采用多种现代分析手段研究了烟酰胺腺嘌呤二核苷酸磷酸(NADP+)与纳米氧化铝(γ-Al2O3)和纳米勃姆石(γ-AlOOH)的相互作用,结果显示NADP+与γ-AlOOH主要通过静电作用相结合,而在γ-Al2O3表面除了静电和氢键作用外,还存在通过铝与磷酸根中的氧配位形成的内层配合物;在3相似文献   

N-[2,6-二氯-4-(1,2,4-噁二唑-3-基)苯基]-2-甲氧基烟酰胺的合成、晶体结构及抗肿瘤活性研究

报道一种新型1,2,4-噁二唑衍生物,N-[2,6-二氯-4-(1,2,4-噁二唑-3-基)苯基]-2-甲氧基烟酰胺（C15H10Cl2N4O3）的合成,其结构通过1H NMR、13C NMR、HRMS以及X-射线单晶衍射进行表征。该晶体结构属于三斜晶系, P 1(—) 空间群,晶胞参数 a = 7.1291 (9), b = 8.4352 (10), c = 14.0021 (18) ?, α = 73.834 (3), β = 77.407 (3), γ = 70.019 (3)°, Mr = 366.18, V = 752.97 (16) ?3, Z = 2, Dc = 1.611 g/cm3, μ(MoKα) = 0.454 mm-1, F(000) = 372.0 , 晶体尺寸为 0.36 × 0.2 × 0.1 mm,Rint = 0.023。初步活性研究发现,该化合物对LoVo, A549, SK-BR-3, HeLa这四种肿瘤细胞株具有明显的抑制作用,尤其是对HeLa细胞的抑制活性与阳性药物5-氟尿嘧啶 (5-FU)相当。     

微流控芯片简易安培检测器的制作及对烟酰胺片中烟酰胺的测定

搭建了微流控芯片简易安培检测器,并用于市售药品烟酰胺片中烟酰胺含量的测定。由碳纳米管微圆盘电极和钛管组成集成双电极,中间的碳纳米管微圆盘电极作为安培检测的工作电极,外套的钛管既作为安培检测的对极,又充当分离高压电源的地极,使其结构更加简化和微型化。优化了缓冲溶液种类、浓度,分离电压及进样时间等实验条件。结果表明,在10 mmol·L-1磷酸盐缓冲液(pH 7.8)中,进样10 s,在2.0kV电压下分离,烟酰胺在2 min内可实现较好的分离和检测,其线性范围为10~600μmol·L-1,检出限(S/N=3)为5.0μmol·L-1,相对标准偏差(RSD)为3.0%,平均加标回收率为99.1%。该装置实现了微型化和集成化,并具有检测灵敏度较高、选择性好、成本低等特点,可用于药品的质量控制。     

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC₅₀ values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC₅₀ value of 1.4µM, when compared to Olaparib (IC₅₀ = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC₅₀ values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.     

Beyond labels: A review of the application of quantum dots as integrated components of assays, bioprobes, and biosensors utilizing optical transduction

A comprehensive review of the development of assays, bioprobes, and biosensors using quantum dots (QDs) as integrated components is presented. In contrast to a QD that is selectively introduced as a label, an integrated QD is one that is present in a system throughout a bioanalysis, and simultaneously has a role in transduction and as a scaffold for biorecognition. Through a diverse array of coatings and bioconjugation strategies, it is possible to use QDs as a scaffold for biorecognition events. The modulation of QD luminescence provides the opportunity for the transduction of these events via fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), charge transfer quenching, and electrochemiluminescence (ECL). An overview of the basic concepts and principles underlying the use of QDs with each of these transduction methods is provided, along with many examples of their application in biological sensing. The latter include: the detection of small molecules using enzyme-linked methods, or using aptamers as affinity probes; the detection of proteins via immunoassays or aptamers; nucleic acid hybridization assays; and assays for protease or nuclease activity. Strategies for multiplexed detection are highlighted among these examples. Although the majority of developments to date have been in vitro, QD-based methods for ex vivo biological sensing are emerging. Some special attention is given to the development of solid-phase assays, which offer certain advantages over their solution-phase counterparts.