The interplay between hydrogen bonds and stacking/T-type interactions in molecular cocrystals.

Area of Science:

• Solid-state chemistry
• Crystallography
• Materials science

Background:

• Supramolecular synthons and hydrogen bonds have historically dominated cocrystal formation understanding.
• The precise role and dominance of hydrogen bonds in molecular cocrystals require further investigation.

Purpose of the Study:

• To analyze the relative importance of different intermolecular interactions in 1:1 two-component cocrystals.
• To re-evaluate the traditional focus on hydrogen bonds in crystal engineering and cocrystal design.

Main Methods:

• Extensive analysis of 1:1 two-component cocrystals within the Cambridge Structural Database.
• Quantification and comparison of hydrogen bonding, stacking, and T-type interactions in cocrystal dimers.

Main Results:

• Stacking and T-type interactions are as important, if not more so, than hydrogen bonds in molecular cocrystals.
• Only 20% of analyzed cocrystal dimers solely involved strong hydrogen bonds; over 50% included stacking/T-type interactions.
• Both hydrogen bonding and stacking/T-type interactions contribute equally to cocrystal lattice stabilization.

Conclusions:

• Crystal engineering and cocrystal design should not exclusively focus on hydrogen bonds.
• Future strategies must incorporate the optimization of both hydrogen bonding and stacking/T-type interactions for effective cocrystal stabilization.