A long-wavelength fluorescent chemodosimeter selective for Cu(II) ion in water
A long-wavelength fluorescent chemodosimeter selective for Cu(II) ion in water
复制标题
DOI：
10.1021/ja971221g
复制
发表时间：
1997-08-06
影响因子：
15
通讯作者：
Czarnik, AW
中科院分区：
文献类型：
--
作者：
Dujols, V;Ford, F;Czarnik, AW
化学剂量计是一种分子大小或更大的装置，它利用非生物受体来实现分析物识别，同时伴有人类可观察到的信号的不可逆转导。在荧光化学剂量计中，这个信号就是荧光。理想的荧光化学剂量计的特性与荧光化学传感器相似，除了实时响应仍然是可取的，该响应反映了对分析物的累积暴露，因此是不可逆转的。在本文中，我们报道了一种新的荧光化学剂量计的设计和合成，该化学剂量计在罗丹明样发射波长下显示出有用的大选择性和信号强度。Cu （II）离子对多种聚aza配体表现出非常高的亲和力（例如，Keq） 6.3× 10 24 M-1在pH为72时对cyclen)，但不幸的是，各种其他过渡金属离子也表现出稍低的亲和力。然而，Cu （II）离子促进r -氨基酸酯(1)水解的速率远高于其他金属离子（方案1），这一反应的一个关键特征是螯合物(2)的中介作用。对于大多数r -氨基酸酯，在室温和中性pH下，在合理的反应物浓度下，水解在几秒钟内完成，产生Cu (II)， r -氨基酸螯合物（3；通常是1:2的化学计量）作为产物。基于时间的选择性，而不是基于结合/自由比，最终更容易降低到剂量学应用的实践中，因为更高浓度的指示剂（导致更大的信号）可以在竞争分析物的条件下使用而不必担心饱和。我们设想类似的分子识别/反应性基序可能被纳入到荧光团衍生物中，这样Cu （II）络合会导致荧光增加。方案2描述了我们的方法。罗丹明B肼(4)由罗丹明B与pocl3反应，收率为80%，未经肼纯化，4由乙腈/水结晶后为无色无荧光物质。我们假设化合物4的肼基可以通过与r -氨基酯的相似行为来识别Cu （II）。酰肼、羟肟酸和o -酰基羟胺都能结合Cu (II)，从而增强转酰基化反应活性。将Cu (OAc) 2加入到无色的肼4乙腈溶液中，罗丹明B的粉红色和荧光特性立即出现。由于两者在加入螯合配体cyclen（过量）后都会消失，我们认为乙腈中的Cu （II）与质子在水中诱导类似的罗丹明B平衡的方式大致相同。
Chemodosimeters are devices, molecule-sized or larger, that utilize abiotic receptors to achieve analyte recognition with concomitant irreversible transduction of a human-observable signal. In fluorescent chemodosimeters, that signal is fluorescence. The properties of ideal fluorescent chemodosimeters are similar to those of fluorescent chemosensors, 1 except that while real-time response remains desirable, that response reflects a cumulative exposure to analyte and is therefore not reversible. In this paper, we report the design and synthesis of a new fluorescent chemodosimeter for Cu (II) ion in water that demonstrates usefully large selectivity and signal strength at a rhodamine-like emission wavelength. Cu (II) ion displays very high affinities for various polyaza ligands (eg, Keq) 6.3× 10 24 M-1 toward cyclen at pH 72), but unfortunately a variety of other transition metal ions also display affinities only somewhat lower. However, the Cu (II) ion has been known for almost 50 years to promote the hydrolysis of R-amino acid esters (1) at rates much greater than those of other metal ions (Scheme 1). 3 A key feature of this reaction is the intermediacy of chelate 2. For most R-amino acid esters, hydrolysis is complete within seconds at room temperature and neutral pH under reasonable reactant concentrations, yielding the Cu (II)‚R-amino acid chelate (3; often 1: 2 stoichiometry) as product. Selectivity based on time, rather than on bound/free ratio, is ultimately easier to reduce to practice for dosimetry applications, as higher concentrations of the indicator (leading to larger signals) can be used without fear of saturation under conditions of competing analytes. We envisioned that a similar molecular recognition/reactivity motif might be incorporated into a fluorophore derivative, such that Cu (II) complexation would lead to a fluorescence increase. Our approach is depicted in Scheme 2. Rhodamine B hydrazide (4), prepared in 80% yield by the reaction of rhodamine B withPOCl3 followed without purification by hydrazine, 4 is a colorless, nonfluorescent substance after crystallization from acetonitrile/water. We hypothesized that the hydrazide group of compound 4 would provide recognition for the Cu (II) by analogy to its behavior with R-amino esters. Hydrazides, hydroxamic acids, and O-acyl hydroxylamines are all known to bind Cu (II) thusly with resulting enhanced transacylation reactivity. 5 Upon addition of Cu (OAc) 2 to a colorless solution of hydrazide 4 in acetonitrile, both the pink color and fluorescence characteristic of rhodamine B appear instantly. Because both disappear upon addition of the chelating ligand cyclen (excess), we propose that Cu (II) in acetonitrile induces a 4 a 6 equilibrium in much the same way that the proton induces an analogous rhodamine B equilibrium in water.