The cation-π interaction.
The cation-π interaction.
复制标题
DOI：
10.1021/ar300265y
复制
发表时间：
2013-04-16
影响因子：
18.3
通讯作者：
Dougherty, Dennis A.
中科院分区：
文献类型：
--
作者：
Dougherty, Dennis A.
化学界现在认识到阳离子-π相互作用是分子识别的主要力量，在决定大分子结构和药物-受体相互作用中加入疏水效应，氢键和离子对。这个帐户提供了作者对阳离子-π相互作用的知识起源和基本性质的看法。早期对环番的研究表明，如果疏水空腔与π系统排列在一起，水溶性阳离子分子将放弃水溶剂化而进入疏水空腔。重要的气相研究确立了阳离子-π相互作用的基本性质。阳离子-π相互作用的强度- Li+以38 kcal/mol的结合能与苯结合; NH 4+以19 kcal/mol-将其与在苯二聚体或水-苯络合物中观察到的较弱的极性-π相互作用区分开来。除了在气相研究中阳离子-π相互作用的实质性内在强度之外，阳离子-π相互作用在水性介质和生物条件下仍然具有能量显著性。许多研究表明，阳离子-π相互作用可以使结合能提高2 - 5 kcal/mol，使其在药物-受体和蛋白质-蛋白质相互作用中与氢键和离子对竞争。与涉及芳族系统的其他非共价相互作用一样，阳离子-π相互作用包括大量的静电分量。像苯（乙烯）这样的分子的六（四）个Cδ−-Hδ+键偶极联合收割机在π系统的表面上产生一个负静电势区域。简单的静电促进了阳离子对表面的自然吸引。（气相）结合能的趋势是Li+>Na+>K+>Rb+：随着离子变大，电荷分散在更大的球体上，结合相互作用减弱，这是经典的静电效应。另一方面，极化率并不能定义这些相互作用。环己烷比苯更易极化，但阳离子粘合剂明显较差。许多研究已经记录了蛋白质结构中的阳离子-π相互作用，其中Lys或Arg侧链与Phe，Tyr或Trp相互作用。此外，无数的研究已经确立了阳离子-π相互作用在一系列生物过程中的重要性。我们的工作集中在分子神经生物学上，我们已经证明神经递质通常使用阳离子-π相互作用来结合它们的受体。我们还表明，许多药物-受体相互作用涉及阳离子-π相互作用。阳离子-π相互作用在尼古丁与大脑中ACh受体的结合中起着关键作用，这是一个特别重要的案例。其他研究人员已经在识别“组蛋白密码”、萜烯生物合成、化学催化和许多其他系统中建立了重要的阳离子-π相互作用。
The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author’s perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forgo aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction – Li+ binds to benzene with 38 kcal/mol of binding energy; NH4+ with 19 kcal/mol– distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2 – 5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) Cδ−–Hδ+ bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li+>Na+>K+>Rb+: as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is more polarizable than benzene, but a decidedly poorer cation binder. Many studies have documented cation-π interactions in protein structures, where Lys or Arg side chains interact with Phe, Tyr, or Trp. In addition, countless studies have established the importance of cation-π interaction in a range of biological processes. Our work has focused on molecular neurobiology, and we have shown that neurotransmitters generally use a cation-π interaction to bind to their receptors. We have also shown that many drug-receptor interactions involve cation-π interactions. A cation-π interaction plays a critical role in the binding of nicotine to ACh receptors in the brain, an especially significant case. Other researchers have established important cation-π interactions in the recognition of the “histone code,” in terpene biosynthesis, in chemical catalysis, and in many other systems.
登录
查看更多内容
影响因子：
3.5
作者：
BURLEY, SK;PETSKO, GA
通讯作者：
PETSKO, GA
影响因子：
5.6
作者：
LEVITT, M;PERUTZ, MF
通讯作者：
PERUTZ, MF
影响因子：
15
作者：
Mecozzi, S;West, AP;Dougherty, DA
通讯作者：
Dougherty, DA
影响因子：
2.9
作者：
Crowley, PB;Golovin, A
通讯作者：
Golovin, A
影响因子：
15
作者：
HUNTER, CA;SANDERS, JKM
通讯作者：
SANDERS, JKM