Department of Chemistry - BMC, Uppsala University, SE-751, 23, Uppsala, Sweden.
Chemistry. 2022 Jan 24;28(5):e202103559. doi: 10.1002/chem.202103559. Epub 2021 Dec 13.
Detection and characterisation of very weak, non-covalent interactions in solution is inherently challenging. Low affinity, short complex lifetime and a constant battle against entropy brings even the most sensitive spectroscopic methods to their knees. Herein we introduce a strategy for the accurate experimental description of weak chemical forces in solution. Its scope is demonstrated by the detailed geometric and thermodynamic characterisation of the weak halogen bond of a non-fluorinated aryl iodide and an ether oxygen (0.6 kJ mol ). Our approach makes use of the entropic advantage of studying a weak force intramolecularly, embedded into a cooperatively folding system, and of the combined use of NOE- and RDC-based ensemble analyses to accurately describe the orientation of the donor and acceptor sites. Thermodynamic constants (ΔG, ΔH and ΔS), describing the specific interaction, were derived from variable temperature chemical shift analysis. We present a methodology for the experimental investigation of remarkably weak halogen bonds and other related weak forces in solution, paving the way for their improved understanding and strategic use in chemistry and biology.
在溶液中检测和描述非常弱的非共价相互作用具有内在的挑战性。低亲和力、短的复合物寿命以及与熵的持续斗争使得即使是最灵敏的光谱方法也无能为力。在此，我们介绍了一种用于准确描述溶液中弱化学力的实验策略。其范围通过对非氟化芳基碘化物和醚氧（0.6 kJ mol）的弱卤键的详细几何和热力学特性来证明。我们的方法利用了在协同折叠系统中研究弱力的熵优势，以及结合使用 NOE 和 RDC 基整体分析来准确描述供体和受体位点的取向。描述特定相互作用的热力学常数（ΔG、ΔH 和 ΔS）是通过变温化学位移分析得出的。我们提出了一种用于实验研究溶液中非常弱的卤键和其他相关弱相互作用的方法，为更好地理解和在化学和生物学中战略性地利用它们铺平了道路。
