The chemical cell biology of zinc: structure and intracellular fluorescence of a zinc-quinolinesulfonamide complex
The chemical cell biology of zinc: structure and intracellular fluorescence of a zinc-quinolinesulfonamide complex
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DOI：
10.1007/s007750050350
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发表时间：
1999-12-01
影响因子：
3
通讯作者：
O'Halloran, TV
中科院分区：
文献类型：
--
作者：
Nasir, MS;Fahrni, CJ;O'Halloran, TV
基于6-甲氧基-8-对甲苯磺酰氨基喹啉的荧光透性化合物TSQ是潜在的细胞内锌化学的强有力探针;然而，金属配合物的结构、热力学和化学计量以及Zn（II）识别的分子基础仍然是开放的问题。为了解决这些问题，我们报道了TSQ衍生物的Zn（II）配合物的第一个结构表征，即2-甲基-6-甲氧基-8-对甲苯磺酰氨基-喹啉（3），并描述了其不寻常的配位化学。3与锌的荧光络合物的晶体结构揭示了2：1的化学计量比，其中来自每个配体的两个氮的二齿配位产生高度扭曲的四面体Zn（II）中心。锌络合物中的两个磺酰胺基都从锌上倾斜，为酰胺氮的配位腾出空间。Zn-O（2）和Zn-O（4）的距离基本上是非键合的（分别为3.06和3.10埃）。相对于理想四面体中心的109度角，键角[N（1）Zn-N（2）83.5度和N（3）-Zn-N（4）83.0度]相当小。该结果提供了对TSQ衍生物锌喹的锌结合模式的洞察，其中甲基取代喹啉环的2-位中的氢。甲基和磺酰胺氧原子明显阻碍了正方形平面和八面体配合物的形成。我们还表明，在DMSO-水（80/20 w/w）中3的Zn（II）络合物表现出与锌喹类似的总体结合稳定性（log β（2）=18.24+/-0.02）。荧光显微镜检查表明，每个家庭的这些成员区分一组类似的锌（II）富集的车厢，是常见的所有真核细胞检查到目前为止，并进一步表明，酯功能是不需要观察这些无处不在的锌负载的车厢。结合的结构，热力学和生理的结果提供了一个基础设计的其他Zn（II）特异性膜渗透探针与一系列的Zn（II）的亲和力和生物物理性质。
Fluorescent cell-permeant compounds based on 6-methoxy-8-p-toluenesulfonamido-quinoline, TSQ, are potentially powerful probes of intracellular zinc chemistry; however, the structure, thermodynamics, and stoichiometry of the metal complexes, and the molecular basis of Zn(II) recognition, remain open issues, To address these, we report the first structural characterization of a Zn(II) complex of a TSQ derivative, namely 2-methyl-6-methoxy-8-p-toluenesulfonamido-quinoline (3) and describe its unusual coordination chemistry. The crystal structure of the fluorescent complex of 3 with zinc reveals a 2:1 stoichiometry wherein bidentate coordination of two nitrogens from each ligand gives rise to a highly distorted tetrahedral Zn(II) center. Both sulfonamido groups in the zinc complex are tilted away from zinc to make room for coordination of the amide nitrogens. Zn-O(2) and Zn-O(4) distances are essentially nonbonding (3.06 and 3.10 Angstrom, respectively). The bond angles [N(1)Zn-N(2) 83.5 degrees and N(3)-Zn-N(4) 83.0 degrees] are quite small relative to the 109 degrees angle of an ideal tetrahedral center. This result provides an insight into the zinc-binding mode of the TSQ derivative zinquin, in which a methyl group replaces the hydrogen in the 2-position of the quinoline ring. The methyl group and sulfonamide oxygen atoms clearly hinder formation of both square planar and octahedral complexes. We also show here that the Zn(II) complex of 3 in DMSO-water (80/20 w/w) exhibits an overall binding stability (log beta(2)=18.24+/-0.02) similar to zinquin. Fluorescence microscopy suggests that each of these members of this family demarks a similar set of Zn(II)-enriched compartments that are common to all eukaryotic cells examined to date, and further shows that the ester function is not required for observation of these ubiquitous Zn-loaded compartments. The combined structural, thermodynamic, and physiological results provide a basis for design of other Zn(II)-specific membrane permeant probes with a range of Zn(II) affinities and photophysical properties.