^1^4C-加速器质谱法研究NNK与血红蛋白的体内加 合作用

用^1^4C-加速器质谱法(AMS)研究了香烟中尼古丁的亚硝基衍生物4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮(NNK)与小鼠体内血红蛋白(Hb)的加合作用,给出了加合剂量响应曲线。NNK剂量在0.01～0.1μg/kgb.w.范围内,加合水平基本上是一样的;而在0.1～3.0μg/kgb.w.范围内,加合物数量与NNK剂量之间呈1g/1g表示的线性关系。同时研究发现一次性给药的NNK-Hb加合物在小鼠体内的衰减表现为快、慢两个阶段,前3天内衰减很快,3天后衰减不明显。     

异硫氰酸荧光素-人血清白蛋白标记物化学发光反应的研究

采用反相流动注射分析方法,研究了异硫氰酸荧光素（FITC）－人血清白蛋白（HSA）标记物的化学发光性能和反应的最佳条件,建立了化学发光测定人血清白蛋白的新方法。体系的化学发光强度与人血清白蛋白的含量在0．08－16μg/mL内呈线性关系,方法的检出限为0．04μg/mL。讨论了蛋白质标记物化学发光性增强的原因。     

某些变色酸双偶氮染料-蛋白质体系的共振瑞利散射及其分析应用

在PH3．4－4．0的缓冲溶液中， 偶氮胂M（AAM）、偶氮氯膦Ⅲ（CPAⅢ）和氯磺酚S（CSPS）等变色酸双偶氮染料及蛋白质本身的共振瑞利散射（RRS）均十分微弱，但这些染料与蛋白质结合形成复合物时能使RRS急剧增强，在400－470nm的范围内呈现高的散射强度，其最大散射波大均位于470nm处，并且散射强度分别在0．36mg/L（CPAⅢ体系）、0－3．8mg/L(AAM体系）和0－4．8mg/L(CSPS体系）的范围内与牛血清白蛋白（BSA）的浓度成正比，方法具有高灵敏度，对于BSA的检出限（σ=3时）分别为18．5μg/L（CPAⅢ）、13．6μg/L（CSPS）和27．9μg/L（AAM）。考察了共存物质的影响，表明方法具有较好的选择性，此法可用于人血清中蛋白质的测定。     

含氮配体与尾式咪唑基铁（Ⅲ）卟啉轴向加合物的低温EPR研究

研究了氯化５－邻（３－（１－咪唑基）丙氧基）苯基－１０，１５，２０－三苯基卟啉合铁（Ⅲ）（ｏ－ｌｍＰｒＴＰＰＦｅ（Ⅲ）Ｃｌ）与咪唑及吡啶类栩体轴向加合物的低温ＥＰＲ，考察了尾端咪唑基对铁（Ⅲ）自旋态及配位环境的影响，结果表明，ｏ－ｌｍＰｒＴＰＰＦｅ（Ⅲ）Ｃｌ的弱吡啶类配体轴向加合物显示了铁（Ⅲ）离子独特的ＥＰＲ磁性，对各加合物的ＥＰＲ参数进行了晶体场分析，求是晶体场分裂参数，并据此分析了各加合物中     

超高效液相色谱-质谱联用技术快速检测二甲基甲酰胺职业接触者血红蛋白中新型生物标志物

建立了二甲基甲酰胺(N,N-dimethyl formamide,DMF)职业接触者血红蛋白中N-甲基氨甲酰加合物超高效液相色谱-质谱联用(UPLC/MS/MS)快速检测方法。准确称取0.1 g血红蛋白样品置于15 mL离心管中,加入40μmol/L3-甲基-异丁基海因(3-methy-5-isobutylhydantion,MIH)内标溶液250μL,再加入HCl-醋酸(2∶1,V/V)溶液4.75 mL,振荡混匀3 min。将试管置于沸水浴中加热降解1 h,取出冷却。混匀后取200μL到96孔板,加入600μL1%甲酸乙腈溶液,混匀。控制真空泵压力,使样品在2~4 min流出。将净化后样品混匀转移到样品瓶,用UPLC/MS/MS检测N-甲基氨甲酰加合物的降解产物3-甲基-异丙基乙内酸脲(3-Methyl-5-isopropylhydantoin,MVH)。质谱采集方式为多反应监测模式,内标法定量。结果表明,MVH浓度在0.01~1.0μmol/L范围内线性关系良好,相关系数为0.999。空白人群血红蛋白MVH加标回收率为97.3%,相对标准偏差为1.7%,血红蛋白中MVH检出限为0.01μmol/g。本方法能很好地应用于二甲基甲酰胺职业接触者血红蛋白中新型生物标志物N-甲基氨甲酰加合物的快速、准确测定。     

2＇-脱氧胞苷-5＇-磷酸羟基加合物的分子结构与电子结构

使用密度泛函理论（DFF）的B3LYP／DZP＋＋研究了羟基自由基与2＇-脱氧胞苷-5’-磷酸（dCMP）的胞嘧啶环加成产物的分子结构与电子结构．结果表明,dCMP胞嘧啶环中各C原子上的单羟基加合物的相对稳定性顺序为C5〉C6≥C4≥C2．加合物的稳定性、自旋密度、静电势以及dCMP的电子密度、静电势、电荷分布分析表明,dCMP遭遇多个羟基自由基攻击时,第一个羟基自由基加在dCMP的C5上,而C6则成为第二个羟基自由基的进攻目标．反应中一旦形成了C2-位单羟基加合物,则极有可能在DNA复制过程中引起致命的基因突变,也可能诱发DNA—DNA以及DNA-蛋白质的链问交联,引起更复杂的损伤．相反,C5、C6-位上单羟基加合物的形成对DNA的稳定性不构成直接威胁．     

铌-桑色素荧光探针猝灭法测定核酸

探讨了应用铌－桑色素（MR）络合物作为荧光探针测定核酸的方法，最大激发峰与发射峰分别位于428nm与497nm；测定的线性范围分别为：HS DNA 10－110μg/L，CT DNA 0-30μg/L,SM DNA 5-60μg/L与Yeast RNA 200-600mg/L；相应的检出限分别为3．8、1．7、0．96与60μg/L，对络合物与DNA的吸收光谱、荧光偏振与热变性行为进行了测量。结果指出：Nb(V)-MR络合物嵌入DNA的双螺旋结构中。     

蛋白质-钼(Ⅵ)-邻苯二酚紫-OP显色体系的研究及应用

建立了一种测定蛋白质的蛋白质－钼（Ⅵ）-邻苯二酚紫－OP显色体系光度法,蛋白质含量在0－50.0μg/mL范围内符合比尔定律。方法已应用于尿液、血清和豆浆中总蛋白测定,加标回收率90％－108％,相对标准偏差1．8％－3．0％（n=5),检出限4．0μg/mL。     

异硫氰酸荧光素-牛血清白蛋白标记物的化学发光反应

采用反相流动注射法，系统地研究了碱性介质中和阳性离子在表面活性剂CTMAB存在下，NaClO氧化异硫氰酸荧光素－牛血清白蛋白标记物的化学发光行为和化学发光反应的条件，提出了反相流动注射化学发光测定牛血清白蛋白的新方法，该法测定牛血清白蛋白线性范围为0．08－16mg/L；检出限为0．032mg/L.。讨论了蛋白质标记物化学发光增强作用的原因。     

灿烂甲酚蓝共振光谱散射法测定脱氧核糖核酸

研究了灿烂甲酚蓝与脱氧核糖核酸（DNA）作用的共振光散射光谱,在pH＝10．8－11．5的范围内,DNA的加入导致灿烂甲酚蓝共振光散射的增强,在347nm处,存在一共振光散射增强峰,其强度与DNA的浓度呈线性关系,据此建立了一种测定DNA的共振光谱散射法。该方法的线范围为80－100μg/L,检出限为23．3μg/L.     

铂配合物与DNA碱基对间相互作用的理论研究

用量子化学方法研究一系列Pt(II)配合物作用于嘌呤碱基N7位点后对Watson-Crick碱基对AT、GC的影响. 计算结果显示铂配体与碱基对AT、GC的作用以静电作用为主，同时极化作用也是影响GC碱基对的重要因素. 静电作用极大地增强了铂化嘌呤碱基与嘧啶碱基间的相互作用，而嘌呤碱基与嘧啶碱基间作用与未铂化碱基对作用相近. Pd(II) 和 Ni(II)的相关研究得到类似的结果. 碱基对间氢键作用“二阶微扰能”分析结果与氢键强弱变化一致.     

C_（60）与含烯丙基胺聚合物加成物的荧光行为

Ｃ_（６０）与含烯丙基胺聚合物加成物的荧光行为田慧洁，陈立桅，姚光庆，金朝霞，李福绵（北京大学化学系北京１００８７１）关键词脂肪胺，Ｃ_（６０），聚烯丙基胺，荧光Ｃ６０是一高度对称的笼状碳簇分子，室温下难以观察到荧光现象［１］，但我们发现它与聚烯丙基胺...     

Synthesis and characterization of a tetramethyl furanone functionalized diiminedioxime,a potential ligand for Cu radiopharmaceuticals,and its copper(II) and nickel(II) complexes

As part of our on-going effort to develop ⁶⁴Cu-based radiopharmaceuticals for PET (positron emission tomography) imaging of multidrug resistance in cancer, we prepared a tetramethylfuranone-functionalized diiminedioxime ligand, TMFPreH (TMFPreH = 4-[3-(4-hydroxyimino-2,2,5,5-dimethyl-dihydro-furan-3-ylideneamino)-propylimino]-2,2,5,5-tetramethyl-dihydrofuran-3(2H)-one oxime) and its Cu(II) and Ni(II) complexes. When the copper(II) complex was prepared from Cu(ClO₄)₂ in ethanol, it was isolated as a Cu(II)-bridged dimer, but when it was prepared from Cu(OAc)₂ and heated in acetone, an unusual example of an acetone adduct of the ligand is formed by reduction of one of the imine double bonds by the solvent. The Ni(II) complex is square pyramidal with the perchlorate counterion at the apex.     

Synthesis and Crystal Structure of Bis[O,O'-di(2-phenylethyl) dithiophosphato](α,α'-bipyridine)copper(Ⅱ)

A ternary adduct Cu[S2P(OCH2CH2Ph)2]2·bipy (bipy=a,a'-bipyridine) was syn-thesized and characterized by elemental analysis,IR and single-crystal X-ray diffraction.The crystal belongs to the trielinic system,space group P(1) with a=10.2320(2),b=11.5249(3),c=18.0916(3) (A),α=98.95(1),β =103.601(1),γ= 91.272(2)°,V= 2044.49(7) (A)3,Z=2,Dc=1.453 g/cm3,T= 153(2) K,C42H44CuN2O4P2S4,Mr= 894.51,λ(MoKa)=0.71073 (A),μ=0.86 mm-1,S=0.999,(△/σ)max=0.002,the final R=0.0243 and wR=0.0704.A total of 9221 unique reflections were collected,of which 8573 with I>2σ(I) were observed.The Cu(Ⅱ) atom is five-coordinated in a rather distorted trigonal bipyramidal geometry (r value=0.537).The Cu-S distances range from 2.3491(4) to 2.4829(4) (A),and the Cu-N distances are 1.9987(12) and 2.0584(11) (A),respectively.An interesting feature of this adduct resides in its two-dimensional (2D) open framework constructing through hydrogen bonding and π-π interactions.     

Synthesis and bioactivity of novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing acrylate and acrylonitrile derivatives

Fifteen novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing Baylis-Hillman adduct derivatives were designed and synthesized. Evaluation of their biological activities showed that methyl 2-((3-(3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenoxy)(phenyl)methyl)acrylate (2g) exhibited efficient broad-spectrum fungicidal activity, with 100% control of wheat powdery mildew and cucumber downy mildew and 98% control of cucumber anthracnose at 400 g ai/ha. Some of the other title compounds 2, 3 and two Baylis-Hillman bromide intermediates (11a, 11b) had moderate to good fungicidal activity.     

A solvent-free synthesis of (dichloroiodo)arenes from iodoarenes

An efficient solid-state oxidation of iodoarenes, ArI, is described using the urea-hydrogen peroxide adduct (UHP), a stable, inexpensive, and easily handled oxidant. The reactions were complete in 15 min at 85 °C. The melts thus obtained were reacted with excess hydrochloric acid to afford crude (dichloroiodo)arenes, ArICl₂, in 64-98% yields.     

Chemo-, regio- and stereoselective addition of triorganoindium reagents to acetates of Baylis-Hillman adducts: a new strategy for the synthesis of (E)- and (Z)-trisubstituted alkenes

The addition of several trialkyl or triarylindium reagents to the acetates of Baylis-Hillman adducts proceeds readily under the catalysis of copper and palladium derivatives. The reactions of trialkylindiums are catalyzed efficiently by CuI whereas additions of triarylindiums produce better results with Pd(PPh₃)₄. The reactions with 3-acetoxy-2-methylenealkanoates provide (E)-alkenes, whereas similar reactions with 3-acetoxy-2-methylenealkanenitriles lead to (Z)-alkenes. All the reactions are highly regio- and stereoselective and high yielding.     

1H,4H-1,4-diborabuckminsterfullerene with pyridine molecules and ytterbium endo-atom

The competition between the ytterbium endo-atom and the pyridine exo-molecules as nucleophiles interacting with the electron-deficient 1H,4H-1,4-diborabuckminsterfullerene was studied using the quantum chemical DFT PBE0 method. The equilibrium structural parameters, dipole moments, IR spectra, and exothermic effects of the formation of the C₅₈B₂•Py₂ adduct and the endohedral Yb@C₅₈B₂•Py₂ complex were determined. The concept of the state of oxidation/reduction of an atom in a chemical compound has been clarified. The localization of the ytterbium(II) under a pair of equivalent carbon atoms bonded to boron(III) atoms is predicted. The introduction of ytterbium(II) into the adduct cavity weakens exo-bonds with pyridine molecules without changing the oxidation state of boron(III). Each nitrogen atom retains a lone electron pair, coordinated by a boron(III). The ytterbium(II) endo-atom retains 14 electrons in f states.     

Kinetics and mechanism of interaction of Pt(II) complex with bio-active ligands and in vitro Pt(II)-sulfur adduct formation in aqueous medium: bio-activity and computational study

Kinetics of interaction between [Pt(pic)(H₂O)₂](ClO₄)₂, 2 (where pic = 2-aminomethylpyridine) with the selected ligands DL-methionine (DL-meth) and DL-penicillamine (DL-pen) have been studied spectrophotometrically in aqueous medium separately as a function of [2] as well as [ligand], pH and temperature at constant ionic strength. The association equilibrium constants (K_E) for the outer sphere complex formation have been evaluated together with the rate constants for the two subsequent steps. Activation parameters (enthalpy of activation ΔH^≠ and entropy of activation ΔS^≠) were calculated from the Eyring equation. An associative mechanism of substitution is proposed for both reactions on the basis of the kinetic observations, evaluated activation parameters, and spectroscopic data. Structural optimizations, HOMO-LUMO energy calculation, and Natural Bond Orbital (NBO) analysis of 2–4 were carried out with Density Functional Theory. Bonding mode of thiol and thio-ether is confirmed by spectroscopic analyses and NBO calculation. Cytotoxic properties of 2–4 were explored on A549 carcinoma cell lines; DNA-binding properties of the complexes were also investigated by gel electrophoresis.     

Luminescence Properties and Analytical Figures of Merits of Benzo(a)Pyrene Guanosine Adduct Adsorbed on α- β- and γ-Cyclodextrin/NaCl,and Trehalose/NaCl Solid Matrices

Abstract

Several cyclodextrin/NaCl and trehalose/NaCl mixtures were investigated as solid matrices for obtaining room-temperature luminescence from a benzo(a)pyrene (B(a)P) guanosine adduct. Room-temperature fluorescence (RTF) and room-temperature phosphorescence (RTP) intensities from the B(a)P-guanosine adduct were compared for different solid matrices. These results showed that 25% trehalose/NaCl, 1% α-cyclodextrin/NaCl, and 1% γ-cyclodextrin/NaCl solid matrices yielded strong fluorescence signals and moderately strong phosphorescence signals at room temperature from the B(a)P-guanosine adduct. In addition, the luminescence properties of pyrene, guanosine, guanosine 3′ -monophosphate free acid and guanosine 3′-monophosphate sodium salt on 1% α-, β-, and γ- cyclodextrin/NaCl solid matrices were obtained.