C-H...O and other weak hydrogen bonds. From crystal engineering to virtual screening

Area of Science:

• Chemistry
• Structural Biology
• Biochemistry

Background:

• Historically, weak hydrogen bonds (X-H...A), particularly those with carbon donors (X=C) and pi-system acceptors (A), were largely disregarded.
• Before the 1980s, these interactions were considered insignificant in chemical and biological systems.
• A paradigm shift occurred in the early 1980s, leading to increased recognition of their importance.

Purpose of the Study:

• To highlight the evolving understanding of weak hydrogen bonds.
• To emphasize their significance in various molecular structures.
• To connect this knowledge to modern applications in biomolecular studies and drug design.

Main Methods:

• Review of historical scientific literature and crystallographic data.
• Analysis of small molecule crystal structures and solution-state studies.
• Application of established knowledge to contemporary biomolecular structure elucidation.

Main Results:

• Weak C-H...pi hydrogen bonds are now understood to play a significant role in stabilizing molecular structures.
• These interactions are prevalent in both crystalline solids and solution phases.
• The recognition of these bonds has advanced the field of structural biology.

Conclusions:

• Weak hydrogen bonds, once dismissed, are now integral to understanding molecular interactions.
• Knowledge of C-H...pi interactions is vital for deciphering biomolecular structures.
• This understanding has direct implications for structure-based drug design strategies.