Experimental dissection of dispersion energies from electrostatic contributions and solvent effects in face-to-face pi-stacking complexes

我们提出了一个新的实验工具箱，用于评估面对面的“堆叠”芳香族系统的结合能，这将有助于分离典型的π-π复合物的静电色散贡献。我们的方法是对现有实验方法的补充，例如小分子缔合物的研究，分子平衡技术或双突变体循环分析，迄今为止，在仔细研究关于π-π堆积相互作用的竞争性理论模型时，这些理论模型还没有完全得出结论。脲和合适的芳族组分将用作结合第二芳族客体的受体部分。在该设计中，芳族化合物（即轮黄烷化的芳族化合物）和进入的第二芳族客体都保持面对面取向（=>高几何控制），并且各自几乎完全被屏蔽而不与溶剂分子接触（=>溶剂化对总π-π堆积能的影响最小化）。我们还提出了一个路径如何结合伙伴的去溶剂化能量成本可以实验占，而不需要计算处理。高几何控制和溶剂化效应的扣除是重要的优势，比其他缔合复合物为基础的研究。此外，生成数据库将是直接的，因为第二芳香族结合配偶体可以容易地混合在其中并且不需要共价连接，如分子平衡的情况。事实上，我们的超分子方法也避免了探测“非最佳”结合几何形状，这可能是共价分子平衡设置的一个缺点。在拟议的研究路线中，我们将首先制备轮黄酸配合物，然后通过等温滴定量热法（ITC）测量它们与芳香族第二客体形成的π-π-复合物的结合构象和游离构象。直接获得结合熵将有助于与计算的π-π相互作用能进行比较，因为计算上难以处理的熵分量可以被忽略。获得自由能（和熵）将提供有价值的数据集，以测试未来改进的理论模型。有关π-π堆积几何形状的信息将通过基于结构的方法获得，例如溶液中的NMR光谱和结晶复合物的X射线衍射结构分析。通过系统地改变芳香族结合伙伴，包括具有典型的“极性”取代基或具有“分散体供体”的系统，我们的目标是对面对面的π-π相互作用基序的静电和分散效应进行实验分离。这项研究将补充新出现的图片的分散相互作用的重要性，分子识别和自组装。

We propose a novel experimental toolbox for evaluating the binding energies of face-to-face “stacking” aromatic systems, which will be of help to separate electrostatic from dispersive contributions for typical pi-pi complexes. Our approach is complementary to existing experimental approaches, e.g. studies with association complexes of small molecules, the molecular balance technique or the double mutant cycle analysis, which have to date not been fully conclusive in scrutinizing competing theoretical models about pi-pi stacking interactions.Stable and geometrically well-defined rotaxanated complexes of the large macrocycle cucurbit[8]uril and a suitable aromatic component will serve as the receptor moiety for binding a second aromatic guest. In this design, both aromatic compounds, i.e. the rotaxanated one, and the incoming second aromatic guest, are hold in a face-to-face orientation (=> high geometric control) and are each almost completely shielded from contact with solvent molecules (=> minimization of solvation effects on the overall pi-pi stacking energy). We also propose a path how the desolvation energy cost of the binding partners can be experimentally accounted for without the need for computational treatments. Both the high geometric control and the subtraction of solvation effects are important advantages over other association-complex-based studies. Furthermore, it will be straightforward to generate a data library, because the second aromatic binding partner can be readily mixed in and does not need to be covalently tethered, as is the case for molecular-balances. In fact, our supramolecular approach also avoids probing a “non-optimal” binding geometry, which can be a shortcoming for covalent molecular-balance setups.In the proposed line of research, we will first prepare the rotaxanated complexes and will then measure by isothermal titration calorimetry (ITC) the binding enthalpies and free enthalpies of their pi-pi-complex formation with aromatic second guests. Having direct access to binding enthalpies will facilitate the comparison to computed pi-pi interaction energies, as the computationally difficult to treat entropic component can be disregarded. Having access to free energies (and thus entropies) will provide a valuable data sets to test future improved theoretical models.Information about the pi-pi stacking geometry will be obtained by structure-based methods such as NMR spectroscopy in solution and X-ray diffraction structure analysis of crystallized complexes. By systematically varying both the aromatic binding partners, including systems with typical “polar” substituents or with “dispersion donors”, we will aim towards an experimental separation of electrostatic and dispersive effects for the face-to-face pi-pi interaction motif. This study will complement the emerging picture of the importance of dispersive interactions for molecular recognition and self-assembly.