Molecular recognition in different environments: β-cyclodextrin dimer formation in organic solvents

Area of Science:

• Biomolecular interactions
• Supramolecular chemistry
• Computational chemistry

Background:

• Macromolecular complexation involves electrostatic, van der Waals, and entropic forces.
• Hydrogen bonds are crucial for biomolecular interactions.
• Beta-cyclodextrin (β-CD) is a cyclic oligosaccharide with a hydrophobic cavity, widely used in various applications.

Purpose of the Study:

• To investigate hydrogen bond (HB) orientations in free β-CD and its head-to-head dimer formation.
• To determine the binding affinity of β-CD monomers in different solvents and with guest molecules.
• To understand the solvent-dependent and guest-modulated nature of β-CD dimerization.

Main Methods:

• Molecular dynamics (MD) simulations were employed to study HB orientations.
• Umbrella sampling simulations were used to calculate potentials of mean force for dimer dissociation.
• 10 different solvents were used to cover a wide range of polarities.

Main Results:

• HB orientations were validated against experimental data in water and DMSO.
• Fast HB exchange was observed in water, while slower or no exchange occurred in other solvents.
• Dimer stability was found to be solvent-dependent; polar solvents weakened dimer binding, while guest molecules enhanced it.

Conclusions:

• β-CD dimerization is significantly influenced by solvent properties and the presence of guest molecules.
• Intermolecular HBs are key to dimer stability, with polar solvents disrupting them.
• Implicit solvent models may require reparameterization for accurate binding energy predictions in non-aqueous solvents.