Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II
Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II
复制标题
DOI：
10.1021/ja011034p
复制
发表时间：
2001-10-03
影响因子：
15
通讯作者：
Christianson, DW
中科院分区：
文献类型：
--
作者：
Kim, CY;Chandra, PP;Christianson, DW
在Phe-131-->瓦尔碳酸酐酶II的晶格骨架内探测了11种不同的氟代芳香族抑制剂的分子间相互作用。缓蚀剂苄基环上氟取代的程度和模式调节其大小、形状和电子特性。反过来，这些特性影响晶格中结合的两种不同抑制剂分子的氟芳环之间的分子间相互作用的几何形状，如通过X射线晶体学所确定的。根据氟取代的程度和模式，我们观察到面对面（芳香族-芳香族）的相互作用，原子面对面（羰基-芳香族）的相互作用，或根本没有相互作用。这些相互作用的几何形状进行了分析方面的货车范德华，静电，和可能的电荷转移效应。对于在这项研究中的芳香族-芳香族相互作用的研究，与芳香环四极专门“调谐”的程度和模式的双极性，结构的结果表明，伦敦力和电荷转移络合占主导地位的弱极性静电相互作用的芳香环对协会。
Intermolecular interactions of eleven different fluoroaromatic inhibitors are probed within the scaffolding of the crystal lattice of Phe-131-->Val carbonic anhydrase II. The degree and pattern of fluorine substitution on the inhibitor benzyl ring modulate its size, shape, and electronic character. In turn, these properties affect the geometry of intermolecular interactions between the fluoroaromatic rings of two different inhibitor molecules bound in the crystal lattice, as determined by X-ray crystallography. Depending on the degree and pattern of fluorine substitution, we observe a face-to-face (aromatic-aromatic) interaction, an atom-to-face (carbonyl-aromatic) interaction, or no interaction at all. These interaction geometries are analyzed with regard to van der Waals, electrostatic, and possible charge-transfer effects. For the aromatic - aromatic interactions investigated in this study, with aromatic ring quadrupoles specifically "tuned" by the degree and pattern of fluorination, the structural results suggest that London forces and charge-transfer complexation dominate over weakly polar electrostatic interactions in the association of aromatic ring pairs.