Does a halogen bond require positive potential on the acid and negative potential on the base?

Area of Science:

• Chemistry
• Physical Chemistry
• Supramolecular Chemistry

Background:

• Halogen bonding (XB) typically involves the interaction between a positively charged region (σ-hole) on a Lewis acid and a negatively charged region (lone pair or π-bond) on a Lewis base.
• This electrostatic interaction is considered the primary driving force for halogen bond formation.

Purpose of the Study:

• To investigate the possibility and nature of halogen bonds under non-traditional electrostatic conditions.
• To explore scenarios where classical Coulombic repulsion might be expected but attractive interactions still occur.

Main Methods:

• Utilized quantum chemical calculations on model systems to analyze electronic structures and electrostatic potentials.
• Examined the influence of substituent effects on the Lewis base to alter its potential distribution.
• Investigated the reverse scenario involving a negatively charged σ-hole on the Lewis acid.

Main Results:

• Demonstrated that halogen bonds can form even when the base possesses a positive potential in its lone pair or π-bond region due to electron-withdrawing substituents.
• Showed that a negatively charged σ-hole on the Lewis acid can interact with a negatively charged lone pair on the base, forming a weak but attractive XB.
• Observed that the strength of these non-classical halogen bonds is remarkably insensitive to variations in the Lewis acid's σ-hole depth or the base's potential sign.

Conclusions:

• Challenges the conventional requirement of positive-negative electrostatic potential matching for halogen bond formation.
• Highlights the existence and surprising robustness of non-classical halogen bonds driven by factors beyond simple Coulombic attraction.
• Suggests a broader understanding of halogen bonding applicable to diverse chemical systems and drug design.