How Do Distance and Solvent Affect Halogen Bonding Involving Negatively Charged Donors?

Area of Science:

• Chemical Physics
• Computational Chemistry
• Molecular Interactions

Background:

• Halogen bonding is a stable interaction involving organohalogens and electron donors, particularly in polar environments.
• The distance between the negative charge center and the halogen atom in organohalogens can vary significantly.
• Previous studies indicate the importance of environmental polarity on halogen bond strength.

Purpose of the Study:

• To investigate the effect of distance between a negative charge center and a halogen atom on halogen bonding strength.
• To explore the influence of solvent polarity on halogen bonding involving negatively charged donors.
• To understand the underlying electronic and electrostatic contributions to halogen bonding.

Main Methods:

• Design and computational modeling of 4-halophenyl-conjugated polyene acid and ammonia systems.
• Quantum mechanics (QM) calculations to determine bonding energies and characteristics.
• Energy decomposition analysis (EDA) to quantify electrostatic and orbital interactions.
• Natural bond orbital (NBO) calculations for electron transfer analysis.
• QM/molecular mechanics (QM/MM) to simulate protein binding pocket environments.

Main Results:

• Halogen bond strength increases with the distance between the negative charge center and the halogen atom.
• Electrostatic interactions are the primary contributor (44-56%) to binding, followed by orbital interactions (42-36%).
• Electron transfer occurs from acceptor to donor, with the halogen atom becoming more positive, similar to neutral halogen bonding.
• Polar environments, such as protein binding pockets, enhance the attractive nature of these interactions.

Conclusions:

• The strength of halogen bonding with negatively charged donors is adjustable via distance and environmental polarity.
• These findings offer insights for tuning molecular interactions in material science and drug design.
• Understanding halogen bond modulation is crucial for developing targeted functional materials and pharmaceuticals.