Marton Gabriel, Koenis Mark A J, Liu Hong-Bing, Bewley Carole A, Buma Wybren Jan, Nicu Valentin Paul
Provitam Foundation, Caisului Street 16, Cluj-Napoca, Romania.
Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Angew Chem Int Ed Engl. 2023 Sep 18;62(38):e202307053. doi: 10.1002/anie.202307053. Epub 2023 Jul 10.
Determination of the absolute configuration of chiral molecules is a prerequisite for obtaining a fundamental understanding in any chirality-related field. The interaction with polarised light has proven to be a powerful means to determine this absolute configuration, but its application rests on the comparison between experimental and computed spectra for which the inherent uncertainty in conformational Boltzmann factors has proven to be extremely hard to tackle. Here we present a novel approach that overcomes this issue by combining a genetic algorithm that identifies the relevant conformers by accounting for the uncertainties in DFT relative energies, and a hierarchical clustering algorithm that analyses the trends in the spectra of the considered conformers and identifies on-the-fly when a given chiroptical technique is not able to make reliable predictions. The effectiveness of this approach is demonstrated by considering the challenging cases of papuamine and haliclonadiamine, two bis-indane natural products with eight chiral centres and considerable conformational heterogeneity that could not be assigned unambiguously with current approaches.
确定手性分子的绝对构型是在任何与手性相关的领域获得基本理解的前提条件。与偏振光的相互作用已被证明是确定这种绝对构型的有力手段，但其应用依赖于实验光谱与计算光谱之间的比较，而构象玻尔兹曼因子中固有的不确定性已被证明极难处理。在此，我们提出一种新颖的方法，该方法通过结合一种遗传算法（通过考虑密度泛函理论（DFT）相对能量中的不确定性来识别相关构象异构体）和一种层次聚类算法（分析所考虑构象异构体的光谱趋势，并在给定的手性光学技术无法做出可靠预测时即时识别）来克服这一问题。通过考虑巴普胺和卤氯二胺这两个具有挑战性的案例，证明了该方法的有效性，这两种双茚满天然产物具有八个手性中心且构象异质性较大，目前的方法无法明确指定其构型。
