Natural and synthetic molecules use weak noncovalent forces to preorganize structure and enable remarkable function. Herein, we introduce the intramolecular hydrogen bonded–halogen bond (HB–XB) as a novel method to preorganize halogen bonding (XBing) molecules, while generating a polarization-enhanced XB. Positioning a fluoroaniline between two iodopyridinium XB donors engendered intramolecular hydrogen bonding (HBing) to the electron-rich belt of both XB donors. NMR solution studies established the efficacy of the HB-XB. The receptor with HB–XBs (G2XB) displayed a nearly 9-fold increase in halide binding over control receptors. Gas-phase density functional theory conformational analysis indicated that the amine stabilizes the bidentate conformation. Furthermore, gas-phase interaction energies showed that the bidentate HB–XBs of G2XBme²⁺ are more than 3.2 kcal mol⁻¹ stronger than the XBs in a control without the intramolecular HB. Additionally, crystal structures confirm that HB–XBs form tighter contacts with I⁻ and Br⁻ and produce receptors that are more planar. Collectively the results establish the intramolecular HB–XB as a tractable strategy to preorganize XB molecules and regulate XB strength.

¹H NMR spectroscopic and X-ray crystallographic investigations of a 1,3-bis(4-ethynyl-3-iodopyridinium)benzene scaffold with perrhenate reveal strong halogen bonding in solution, and bidentate association in the solid state. A nearly isostructural host molecule demonstrates significant C–H hydrogen bonding to perrhenate in the same phases.