Luminescent probes of crystal growth: Surface charge and polar axis sense in dye-doped potassium hydrogen phthalate
Luminescent probes of crystal growth: Surface charge and polar axis sense in dye-doped potassium hydrogen phthalate
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DOI：
10.1002/anie.200453839
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Rohl, AL
中科院分区：
文献类型：
--
作者：
Barbon, A;Bellinazzi, M;Rohl, AL
发光标记一直是生物化学家渴望阐明特定非共价相互作用的支柱。[1]溶液中的晶体生长也受特定的非共价相互作用的控制，但发光探针还没有被同样使用。与罗丹明或绿色荧光蛋白共价连接到细胞中的蛋白质并悬挂在细胞质中不同，根据传统智慧，紧密堆积的晶体没有空间容纳这些标签。现在已经确定，即使当客体分子比主体分子大许多倍时，远离平衡的晶体生长也可以驱动混合晶体的形成。[2]我们利用发光探针来可视化客体对邻苯二甲酸氢钾（通常缩写为邻苯二甲酸氢钾）晶面生长的特异性。我们用计算的分子静电势表面（EPS）解释了我们的实验观察结果，这是生物化学家广泛使用的另一种设备，在这种情况下用于评估配体对接位点，[3]很少[4]在晶体生长的研究中应用，因为与评估周期性表面的静电势相关的困难。使用实验和理论串联，我们展示了染料如何响应KAP的表面电荷，同时建立其极轴的绝对意义。KAP晶体在室温下通过自发成核从水溶液中生长为{010}板，具有以下附加形式：{111}，{111}，{110}，偶尔{121}。[5]它们是由钾离子和邻苯二甲酸氢离子的极性人字形阵列交替双层堆叠在空间群Pca 21中的沿着[010]（图1）。所有（hkl）指数所指的极[001]轴的方向已由X射线的异常散射指定。[6]Bijvoet方法类似地应用于本文所述的所有混合晶体。KAP晶体取向并过度生长超过100种微摩尔浓度的染料。[7，8]染色的晶体通常显示出与对发光体具有不同亲和力的小平面一致的颜色图案。因此，染料包含在多面体生长扇区中，通过特定面生长的晶体的子体积。[2]图1显示了两种含有碱性品红（1）和磺酰罗丹明101（2）的代表性混合晶体。我们已经观察到，阳离子如1主要识别{111}生长扇区，而阴离子如2倾向于识别{111}。这些发现不能被简化为严格的规则。已经观察到几个令人困惑的例外，最值得注意的是3，6-二氨基吖啶（3），这是这项工作的重点，它装饰KAP形成显着的“三色”晶体。对于1和2，每个KAP混合晶体只有一端发光（图1），这表明存在极轴。确定极轴方向的其他化学方法包括与气体的反应，[9]热释电晶体中的孔特粉末测试，[10]以及晶体习性，表面形貌和对称性的变化与已知活性的所谓“定制添加剂”。[11]鉴于发光的敏感性，用荧光探针形成混合晶体是一种有吸引力的选择。为了理解1和2对KAP的选择性，我们首先确定了对应于（111）、（111）和（110）面的能量稳定表面。对于任何给定的指数集（hkl），可以有许多离散表面，特别是
Luminescent labels have been a mainstay of biological chemists eager to illuminate specific noncovalent interactions.[1] Crystal growth from solution is also controlled by specific noncovalent interactions, but luminescent probes have not been used likewise. Unlike rhodamine or green fluorescent protein covalently tethered to a protein in a cell and dangled into the cytoplasm, close packed crystals do not have the space, according to conventional wisdom, to accommodate such labels. It is now well established that crystal growth far from equilibrium can drive mixed crystal formation even when guest molecules are many times larger than those of the host.[2] We take advantage of a luminescent probe to visualize the specificity of a guest for growing crystal faces of potassium hydrogen phthalate (commonly abbreviated as KAP for potassium acid phthalate). We have interpreted our experimental observations with calculated molecular electrostatic potential surfaces (EPS), yet another device widely used by biochemists, in this case to evaluate ligand docking sites,[3] that has rarely [4] found application in studies of crystal growth because of the difficulties associated with evaluating the electrostatic potential of a periodic surface. Using experiment and theory in tandem, we show how dyes respond to the surface charges of KAP while at the same time establishing the absolute sense of its polar axis. KAP crystals grow from aqueous solution by spontaneous nucleation at room temperature as {010} plates with the following additional forms:{111},{111},{110}, and occasionally {121}.[5] They are built of alternating bilayers of potassium ions and polar herringbone arrays of hydrogen phthalate ions stacked along [010] in the space group Pca21 (Figure 1). The sense of the polar [001] axis, to which all (hkl) indices refer, has been assigned by anomalous scattering of X-rays.[6] The Bijvoet method was similarly applied to all of the mixed crystals described herein.KAP crystals orient and overgrow more than 100 dyes in micromolar concentrations.[7, 8] Dyed crystals typically show patterns of color consistent with facets that have different affinities for the luminophores. Dyes are thus contained in polyhedral growth sectors, subvolumes of the crystals that have grown through particular faces.[2] Two representative mixed crystals containing basic fuchsin (1) and sulforhodamine 101 (2) are shown in Figure 1. We have observed that cations such as 1 primarily recognize {111} growth sectors while anions such as 2 tend to recognize {111}. These findings cannot be reduced to firm rules. Several puzzling exceptions have been observed, most notably 3, 6-diaminoacridine (3), the focus of this work, that decorates KAP to form remarkable “tricolore” crystals. With 1 and 2, only one end of each KAP mixed crystal is luminescent (Figure 1), which reveals the presence of a polar axis. Other chemical methods for assigning the sense of a polar axis include reactions with gases,[9] the Kundt powder test in pyroelectric crystals,[10] and changes in crystal habit, surface topography, and symmetry with so-called “tailormade additives” of known activity.[11] Given the sensitivity of luminescence, mixed crystal formation with fluorescent probes is an attractive alternative. To understand the selectivity of 1 and 2 for KAP, we first determined the energetically stable surfaces that correspond to the (111),(111), and (110) faces. For any given set of indices (hkl), there can be a number of discrete surfaces, especially