Establishing Halogen-Bond Preferences in Molecules with Multiple Acceptor Sites.

Area of Science:

• Supramolecular Chemistry
• Crystal Engineering
• Organic Chemistry

Background:

• Hydrogen bonds (HBs) and halogen bonds (XBs) are crucial non-covalent interactions in molecular recognition and crystal engineering.
• Understanding the competitive and cooperative interplay between HBs and XBs is essential for designing functional crystalline materials.

Purpose of the Study:

• To investigate the competition between hydrogen bonds and halogen bonds using specific halogen bond donors and amide-based targets.
• To analyze the structural outcomes of co-crystallizing halogen bond donors with various pyridine-containing amide derivatives.

Main Methods:

• Co-crystallization of halogen bond donors (1,4-diiodotetrafluorobenzene and 1,3,5-trifluoro-2,4,6-triiodobenzene) with four series of N-(pyridin-2-yl)amide targets.
• Single-crystal X-ray diffraction (SCXRD) analysis of 13 co-crystals to determine their solid-state structures.
• Comparison of intermolecular interactions in co-crystals versus individual target compounds.

Main Results:

• In N-(pyridin-2-yl)picolinamides (2Pyr-X) co-crystals, intramolecular hydrogen bonds remained intact, while halogen bond donors interacted with pyridine nitrogens or carbonyl oxygens.
• In co-crystals from the other three series (Bz-X, 3Pyr-X, 4Pyr-X), intermolecular hydrogen bonds present in the individual targets were disrupted in 9 out of 10 cases.
• Halogen bond donors preferentially selected pyridine nitrogen atoms (81%) as acceptor sites, followed by carbonyl oxygen (15%) and π-systems (4%).

Conclusions:

• Halogen bond donors exhibit a strong preference for pyridine nitrogen atoms, influencing the overall crystal packing and hydrogen bonding networks.
• The presence and type of hydrogen bonds in the individual components can be modulated or disrupted upon co-crystallization with halogen bond donors.
• This study provides valuable insights into the predictable assembly of co-crystals based on the interplay of halogen and hydrogen bonding interactions.