Pushing the Limits of Characterising a Weak Halogen Bond in Solution

• Published in: Chemistry : a European journal Vol. 28; no. 5; pp. e202103559 - n/a
• Main Authors: Peintner, Stefan, Erdélyi, Máté
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 24-01-2022; John Wiley and Sons Inc
• Subjects: Bonding strength; Chemical equilibrium; Chemistry; Chemistry, Physical; conformation; ensemble analysis; Entropy; halogen bond; Halogens; Iodides; Knee; NAMFIS; NMR spectroscopy; RDC; Temperature; Thermodynamics; RDC; halogen bond; ensemble analysis; conformation; NAMFIS; NMR spectroscopy
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202103559

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−1). 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.
Very weak halogen bonds are excessively difficult to characterise in solution. We present an approach for the detailed NMR spectroscopic description of very weak interactions, providing the solution ensemble of the flexible model compound, the accurate geometry of the binding sites and the corresponding thermodynamic parameters. Here NOE abbreviates nuclear Overhauser effect, RDC corresponds to residual dipolar coupling, and ΔT indicates variable temperature experiments.