Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610 Prague 6, Czech Republic.
Chemphyschem. 2012 Aug 6;13(11):2748-60. doi: 10.1002/cphc.201200201. Epub 2012 Jun 15.
The tryptophan (Trp) aromatic residue in chiral matrices often exhibits a large optical activity and thus provides valuable structural information. However, it can also obscure spectral contributions from other peptide parts. To better understand the induced chirality, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) spectra of Trp-containing cyclic dipeptides c-(Trp-X) (where X = Gly, Ala, Trp, Leu, nLeu, and Pro) are analyzed on the basis of experimental spectra and density functional theory (DFT) computations. The results provide valuable insight into the molecular conformational and spectroscopic behavior of Trp. Whereas the ECD is dominated by Trp π-π* transitions, VCD is dominated by the amide modes, well separated from minor Trp contributions. The ROA signal is the most complex. However, an ROA marker band at 1554 cm(-1) indicates the local χ(2) angle value in this residue, in accordance with previous theoretical predictions. The spectra and computations also indicate that the peptide ring is nonplanar, with a shallow potential so that the nonplanarity is primarily induced by the side chains. Dispersion-corrected DFT calculations provide better results than plain DFT, but comparison with experiment suggests that they overestimate the stability of the folded conformers. Molecular dynamics simulations and NMR results also confirm a limited accuracy of the dispersion-DFT model in nonaqueous solvents. Combination of chiral spectroscopies with theoretical analysis thus significantly enhances the information that can be obtained from the induced chirality of the Trp aromatic residue.
手性基质中的色氨酸（Trp）芳香残基通常表现出较大的光学活性，因此提供了有价值的结构信息。然而，它也可能掩盖其他肽部分的光谱贡献。为了更好地理解诱导手性，基于实验光谱和密度泛函理论（DFT）计算，分析了含有色氨酸的环状二肽 c-(Trp-X)（其中 X = Gly、Ala、Trp、Leu、nLeu 和 Pro）的色氨酸电子圆二色性（ECD）、振动圆二色性（VCD）和拉曼光学活性（ROA）谱。结果为色氨酸的分子构象和光谱行为提供了有价值的见解。虽然 ECD 主要由 Trp π-π*跃迁主导，但 VCD 主要由酰胺模式主导，与较小的 Trp 贡献很好地分离。ROA 信号最为复杂。然而，在 1554cm(-1)处的 ROA 标记带表明该残基中的局部 χ(2)角值，与之前的理论预测一致。光谱和计算还表明，肽环是非平面的，具有浅势，因此非平面性主要由侧链诱导。色散校正的 DFT 计算比普通 DFT 提供了更好的结果，但与实验的比较表明它们高估了折叠构象的稳定性。分子动力学模拟和 NMR 结果也证实了非水溶剂中色散-DFT 模型的有限准确性。因此，手性光谱与理论分析的结合大大增强了可以从色氨酸芳香残基的诱导手性中获得的信息。
