The interplay between hydrogen and halogen bonding: substituent effects and their role in the hydrogen bond enhanced halogen bond

Jiyu Sun, Daniel A. Decato, Vyacheslav S. Bryantsev, Eric A. John, Orion B. Berryman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The hydrogen bond enhanced halogen bond (HBeXB) has recently been used to effectively improve anion binding, organocatalysis, and protein structure/function. In this study, we present the first systematic investigation of substituent effects in the HBeXB. NMR analysis confirmed intramolecular HBing between the amine and the electron-rich belt of the XB donor (N-H⋯I). Gas-phase density functional theory studies showed that the influence of HBing on the halogen atom is more sensitive to substitution on the HB donor ring (R1). The NMR studies revealed that the intramolecular HBing had a significant impact on receptor performance, resulting in a 50-fold improvement. Additionally, linear free energy relationship (LFER) analysis was employed for the first time to study the substituent effect in the HBeXB. The results showed that substituents on the XB donor ring (R2) had a competing effect where electron donating groups strengthened the HB and weakened the XB. Therefore, selecting an appropriate substituent on the adjacent HB donor ring (R1) could be an alternative and effective way to enhance an electron-rich XB donor. X-ray crystallographic analysis demonstrated that intramolecular HBing plays an important role in the receptor adopting the bidentate conformation. Taken together, the findings imply that modifying distal substituents that affect neighboring noncovalent interactions can have a similar impact to conventional para substitution substituent effects.

Original languageEnglish
Pages (from-to)8924-8935
Number of pages12
JournalChemical Science
Volume14
Issue number33
DOIs
StatePublished - Aug 23 2023

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