Department of Chemistry and La Trobe Institute for Molecular Sciences (LIMS), La Trobe University, Bundoora, Victoria, 3086, Australia.
Phys Chem Chem Phys. 2012 Jul 7;14(25):9219-29. doi: 10.1039/c2cp40828g. Epub 2012 May 29.
The neurotransmitter analogue p-aminophenethylamine (APEA) illustrates many of the pitfalls and challenges associated with spectroscopic and conformational analysis of flexible molecules. The combined experimental-theoretical study presented here resolves a long-standing controversy over its conformational energetic preferences. Jet-cooled resonance enhanced two-photon ionisation (R2PI) and IR-UV ion depletion techniques enabled conformer-specific IR spectra in the NH-CH stretch region to be measured for four distinct conformers of APEA. Comparison of spectra with theoretical calculations (including MP2, M06-2X and B3LYP with aug-cc-pVTZ basis sets) allows the two most populated conformers to be unambiguously identified as those having a gauche arrangement of the side chain, which facilitates an NH···π type hydrogen bond. The other two observed conformers are assigned to structures with an anti-side chain. A fifth gauche conformer, predicted to be least stable, is not observed. Comparison with published conformer specific IR spectra of tyramine (Makara et al., J. Phys. Chem. A, 2008, 112, 13463-13469) and Raman spectra of phenylethylamine (Golan et al., J. Chem. Phys., 2009, 131, 024305) reveals an entirely consistent pattern of spectral signatures associated with the four specific conformations of the ethylamine side chain evident in APEA, and aids assignment of the associated CH and NH stretch fundamentals, some of which have very weak IR intensities. Extensive calculations of the relative energetic trends of the five conformers have been carried out. In comparison to the highest level of theory considered, CCSD(T)-F12b/cc-pVDZ-F12, MP2 overestimate the energy difference, whereas DFT significantly underestimates the energetic preference for NH···π stabilised gauche conformers, although inclusion of dispersion (M06-2X, B3LYP-D3) improves the DFT results.
神经递质类似物对氨基苯乙胺（APEA）展示了许多与光谱和构象分析相关的陷阱和挑战，这些问题存在于对柔性分子的研究中。本文提出了一个综合的实验理论研究，解决了关于其构象能量偏好的长期争议。使用喷射冷却的共振增强双光子电离（R2PI）和红外-紫外离子损耗技术，对 APEA 的四个不同构象体进行了 NH-CH 伸缩区域的构象特异性红外光谱测量。将光谱与理论计算（包括 MP2、M06-2X 和 B3LYP 与 aug-cc-pVTZ 基组）进行比较，可以明确识别出两种最常见的构象体，它们的侧链具有 gauche 排列，这有利于 NH···π 型氢键。另外两种观察到的构象体被分配给具有反式侧链的结构。预测最不稳定的第五种 gauche 构象体没有被观察到。与已发表的 tyramine（Makara 等人，J. Phys. Chem. A，2008，112，13463-13469）的构象特异性红外光谱和 phenylethylamine（Golan 等人，J. Chem. Phys.，2009，131，024305）的拉曼光谱进行比较，揭示了与 APEA 中乙基胺侧链的四个特定构象相关的完全一致的光谱特征模式，并有助于相关 CH 和 NH 伸缩基频的分配，其中一些具有非常弱的红外强度。对五种构象体的相对能量趋势进行了广泛的计算。与所考虑的最高理论水平（CCSD(T)-F12b/cc-pVDZ-F12）相比，MP2 高估了能量差异，而 DFT 则大大低估了 NH···π 稳定的 gauche 构象体的能量偏好，尽管包括色散（M06-2X、B3LYP-D3）可以改善 DFT 结果。
