Department of Organic Chemistry, Southern Federal University, Zorge 7, 344090 Rostov-on-Don, Russian Federation.
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
J Org Chem. 2020 Oct 2;85(19):12468-12481. doi: 10.1021/acs.joc.0c01697. Epub 2020 Sep 22.
For the first time, systematic studies of 8-aryl and 8-pyrrolyl derivatives of 1-aminonaphthalene as simple, synthetically available, and nicely preorganized models were conducted for a better understanding the properties of NH···π interactions involved in the stabilization of the secondary and tertiary protein structures as well as the recognition of guest molecules by biological receptors. It was shown that the NH···π binding is especially effective when the NH-donor is a positively charged group, for example, MeNH, and the π-donor is an electron-rich aromatic substituent, in particular, the 1-pyrrolyl or the 4-hydroxyphenyl group. Using protonated tetrafluoroborate salts, a strong counterion effect was demonstrated by means of theoretical calculations. Through several mechanisms, including short CH···F contacts, bifurcation, and long-range dispersion, the counterion promotes considerable structural changes and weakens the NH···π interactions from 12-15 kcal mol in "naked" cations to 5-9 kcal mol in the salts. To this end, 8-(2,5-dimethylpyrrol-1-yl)-,-dimethylnaphthalene-1-ammonium tetrafluoroborate, with the record linearity and shortness (2.07 Å) of the NH···π-centroid bond, was recognized as the most appropriate model with the strongest NH···π interaction ever described.
首次对 1-氨基萘的 8-芳基和 8-吡咯基衍生物进行了系统研究，这些衍生物是简单、可合成且组织良好的模型，以更好地理解涉及二级和三级蛋白质结构稳定以及生物受体对客体分子识别的 NH···π 相互作用的性质。结果表明，当 NH 供体是带正电荷的基团（例如 MeNH），而π 供体是富电子芳香取代基（特别是 1-吡咯基或 4-羟基苯基）时，NH···π 键合特别有效。通过理论计算，使用质子化四氟硼酸盐盐证明了强抗衡离子效应。通过几种机制，包括短 CH···F 接触、分叉和远程分散，抗衡离子促进了相当大的结构变化，并使 NH···π 相互作用从“裸露”阳离子中的 12-15 kcal/mol 减弱到盐中的 5-9 kcal/mol。为此，8-(2,5-二甲基吡咯-1-基)-,-二甲基萘-1-铵四氟硼酸盐，具有记录的线性度和 NH···π-质心键的短度（2.07 Å），被认为是具有最强 NH···π 相互作用的最适宜模型。
