DNA分子“光开关”含钌多吡啶络合物细胞摄取、胞内分布及毒性机理研究

DNA作为遗传信息的载体,了解在细胞核内的组装和结构具有非常重要的意义。目前,使用能够与DNA结合的细胞膜渗透性良好的有机荧光分子作为DNA标记探针是实现这一目标的主要手段。自Barton实验室发现阳离子Ru（Ⅱ）络合物[Ru（bpy）₂（dppz）]²⁺（bpy=2,2'-联吡啶,dppz=多吡啶并吩嗪）能够作为DNA分子"光开关"以来,d⁶八面体多吡啶金属络合物与DNA的结合特性及相关研究,尤其是对这类金属络合物作为高灵敏度和结构特异性DNA探针的研究,便吸引了人们极大的关注。由于这类物质较低的膜渗透性,先前多数研究都只是局限于细胞外,活细胞内DNA直接显像成功的实例较为少见。本课题组发现五氯酚（PCP）和另外两类结构不相关的生化试剂能促进Ru（Ⅱ）多吡啶络合物的细胞特别是细胞核的摄取,[Ru（bpy）₂（dppz）]²⁺/PCP之间的协同核摄取机理可能是形成了较稳定的亲脂性离子对复合物。Ru（Ⅱ）络合物的两种对映异构体在活细胞内与DNA结合后表现出了明显的手性选择性。这是我们首次发现通过以形成离子对复合物的方式将DNA分子"光开关"Ru（Ⅱ）络合物转入活细胞核内并维持其"光开关"效应,可为研究将其他潜在的具有生物医疗效应的细胞膜不通透金属络合物转入细胞内提供一种全新的方法。     

Volumetric behavior of aqueous NaF and KF solutions up to 350‡C and 30 MPa

The volumetric behavior of NaF(aq) and KF(aq) has been studied as a function of temperature up to 627 K and pressures up to 30 MPa using a vibrating-tube flow densitometer. The measured densities were used to derive apparent molar volumesVΦ at concentrations up to 0.9 mol-kg^-1 for NaF and up to 3mol-kg^-1 for KF. Standard partial molar volumes V ₂ ⁰ (NaF)-and V ₂ ⁰ (KF) were obtained by extrapolating VΦ values to infinite dilution using the Pitzer equation truncated at the second virial coefficient. Comparison with related 1:1 and 1:2 electrolytes allows examination of the extent to which the concentration and temperature dependence of the volumes is linked with the size and charge of ions. A semiquantitative estimate of association based on the close similarity of fluorides and hydroxides is made to evaluate the effect of ion-pairing on the volumetric behavior of the fluorides. On leave from the Department of Physical Chemistry, Institute of Chemical Technology, 166 28 Prague 6, Czech Republic.     

Determination Of Chlorpromazine And Its Sulfoxide And 7-Hydroxy Metabolites By Ion-Pair High Pressure Liquid Chromatography

Abstract

An ion-pair HPLC approach with ordinary silica has been applied, with detection by ultraviolet absorption, to the assay of plasma for chlorpromazine and its sulfoxide on the one hand, and for 7-hydroxychlorpromazine (an active metabolite) on the other hand. The respective sample-preparation procedures entail extraction of the plasma with heptane at strongly alkaline pH, or else with diethyl ether at a less alkaline pH and with ensuing back-extraction and re-extraction. For each of the compounds, levels as low as 10 ng. ml^?1 are measurable. The conditions adopted are such that specificity and reproducibility are satisfactory although chlorpromazine and its various metabolites, especially 7-hydroxychlorpromazine, are chemically unstable and, moreover, are readily lost onto glass. With the unorthodox separation system adopted, adsorption rather than partition appears to be the dominant mechanism.     

A direct nitrogen-15 NMR study of praseodymium(III)-nitrate complex formation in aqueous solvent mixtures

A direct, low-temperature nitrogen-15(¹⁵N) NMR technique has been applied to the study of inner-shell complex formation between praseodymium(III) and nitrate ion in aqueous solvent mixtures. In water-acetone mixtures at –95°C, ligand exchange is slow enough to permit the observation of¹⁵N NMR signals for uncomplexed and coordinated nitrate ion, but satisfactory resolution is obtained only by the addition of Freon-12 to these systems for study at –110 to –115°C. Four coordinated nitrate signals are generally observed and a very small signal for an additional complex, or an isomer of one of the others, appears at the highest nitrate concentrations. Signals for the mono-and dinitrato complexes are unambiguously identified, but with the exception of the trinitrato complex, several possibilities exist for the remaining peaks. To overcome excessive viscosity signal broadening, measurements in methanol and ethanol are possible only with praseodymium trifluoromethanesulfonate (triflate). Coordinated nitrate signals in aqueous and anhydrous methanol are observed only for the mono-and dinitrato species, and signal areas indicate a maximum of two moles of nitrate per Pr(III) are complexed. A third signal is evident in the ethanol solution spectra, and the presence of this higher complex was confirmed by area measurement of the fraction of bound nitrate. The extent of complex formation in these solvent systems is attributed to differences in the dielectric constant. A comparison of the complexing tendencies of Pr(III) to other ions studied by this NMR method suggests the possibility of a coordination number change across the lanthanide series. Preliminary¹⁵N NMR results for metal-ion complexes with the isothiocyanate ion are presented.