Siu Fung Ming, Ma Ngai Ling, Tsang Chun Wai
Department of Applied Biology and Chemical Technology and Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Chemistry. 2004 Apr 19;10(8):1966-76. doi: 10.1002/chem.200305519.
To understand the cation-pi interaction in aromatic amino acids and peptides, the binding of M(+) (where M(+) = Li(+), Na(+), and K(+)) to phenylalanine (Phe) is studied at the best level of density functional theory reported so far. The different modes of M(+) binding show the same order of binding affinity (Li(+)>Na(+)>K(+)), in the approximate ratio of 2.2:1.5:1.0. The most stable binding mode is one in which the M(+) is stabilized by a tridentate interaction between the cation and the carbonyl oxygen (O[double bond]C), amino nitrogen (--NH(2)), and aromatic pi ring; the absolute Li(+), Na(+), and K(+) affinities are estimated theoretically to be 275, 201, and 141 kJ mol(-1), respectively. Factors affecting the relative stabilities of various M(+)-Phe binding modes and conformers have been identified, with ion-dipole interaction playing an important role. We found that the trend of pi and non-pi cation bonding distances (Na(+)-pi>Na(+)-N>Na(+)-O and K(+)-pi>K(+)-N>K(+)-O) in our theoretical Na(+)/K(+)-Phe structures are in agreement with the reported X-ray crystal structures of model synthetic receptors (sodium and potassium bound lariat ether complexes), even though the average alkali metal cation-pi distance found in the crystal structures is longer. This difference between the solid and the gas-phase structures can be reconciled by taking the higher coordination number of the cations in the lariat ether complexes into account.
为了理解芳香族氨基酸和肽中的阳离子-π相互作用，我们在目前报道的密度泛函理论的最佳水平上研究了M⁺（其中M⁺ = Li⁺、Na⁺和K⁺）与苯丙氨酸（Phe）的结合。M⁺的不同结合模式显示出相同的结合亲和力顺序（Li⁺>Na⁺>K⁺），近似比例为2.2:1.5:1.0。最稳定的结合模式是阳离子通过与羰基氧（O[双键]C）、氨基氮（--NH₂）和芳香π环之间的三齿相互作用而稳定；理论上估计Li⁺、Na⁺和K⁺的绝对亲和力分别为275、201和141 kJ mol⁻¹。已经确定了影响各种M⁺-Phe结合模式和构象相对稳定性的因素，其中离子-偶极相互作用起着重要作用。我们发现，在我们理论上的Na⁺/K⁺-Phe结构中，π和非π阳离子键距的趋势（Na⁺-π>Na⁺-N>Na⁺-O和K⁺-π>K⁺-N>K⁺-O）与报道的模型合成受体（钠和钾结合的套索醚配合物）的X射线晶体结构一致，尽管在晶体结构中发现的平均碱金属阳离子-π距离更长。考虑到套索醚配合物中阳离子的高配位数，可以解释固相和气相结构之间的这种差异。
