Centre for Theoretical and Computational Chemistry, University of Tromsø, N-9037 Tromsø, Norway.
J Phys Chem A. 2013 Feb 28;117(8):1721-36. doi: 10.1021/jp311151h. Epub 2013 Feb 13.
Increasing precision of contemporary computational methods makes spectroscopies such as vibrational (VCD) and electronic (ECD) circular dichroism attractive for determination of absolute configurations (AC) of organic compounds. This is, however, difficult for polar, flexible molecules with multiple chiral centers. Typically, a combination of several methods provides the best picture of molecular behavior. As a test case, all possible stereoisomers with known AC (RS, SR, SS, and RR) of the cyclic dipeptide cyclo(Arg-Trp) (CAT) were synthesized, and the performances of the ECD, infrared (IR), VCD, Raman, Raman optical activity (ROA), and nuclear magnetic resonance (NMR) techniques for AC determination were investigated. The spectra were interpreted with the aid of density functional theory (DFT) calculations. Folded geometries stabilized by van der Waals and electrostatic interactions between the diketopiperazine (DKP) ring and the indole group are predicted to be preferred for CAT, with more pronounced folding due to Arg-Trp stacking in the case of SS/RR-CAT. The RS/SR isomers prefer a twist-boat puckering of the DKP ring, which is relatively independent of the orientation of the side chains. Calculated conformer-averaged VCD and ECD spectra explain most of the experimentally observed bands and allow for AC determination of the tryptophan side-chain, whereas the stereochemical configuration of the arginine side-chain is visible only in VCD. NMR studies provide characteristic long-range (2)J(C,H) and (3)J(C,H) coupling constants, and nuclear Overhauser effect (NOE) correlations, which in combination with either ECD or VCD also allow for complete AC determination of CAT.
当代计算方法的精度不断提高，使得振动（VCD）和电子（ECD）圆二色性等光谱技术成为确定有机化合物绝对构型（AC）的有吸引力的方法。然而，对于具有多个手性中心的极性、柔性分子来说，这是困难的。通常，几种方法的组合可以提供分子行为的最佳图像。作为一个测试案例，所有具有已知 AC（RS、SR、SS 和 RR）的可能立体异构体的环状二肽环（Arg-Trp）（CAT）都被合成，并研究了 ECD、红外（IR）、VCD、拉曼、拉曼光学活性（ROA）和核磁共振（NMR）技术用于确定 AC 的性能。这些光谱在密度泛函理论（DFT）计算的帮助下进行了解释。预测由二酮哌嗪（DKP）环和吲哚基团之间的范德华和静电相互作用稳定的折叠构象对于 CAT 是优选的，由于 SS/RR-CAT 中 Arg-Trp 堆积，折叠更为明显。RS/SR 异构体更喜欢 DKP 环的扭曲船构象，其相对独立于侧链的取向。计算得到的构象平均 VCD 和 ECD 光谱解释了大部分实验观察到的谱带，并允许对色氨酸侧链进行 AC 确定，而精氨酸侧链的立体化学构型仅在 VCD 中可见。NMR 研究提供了特征的远程（2）J（C，H）和（3）J（C，H）耦合常数以及核 Overhauser 效应（NOE）相关，这些与 ECD 或 VCD 结合使用也允许对 CAT 的完整 AC 进行确定。
