Computational study of multicharged cyclodextrin derivatives with deep cavities for high-affinity host-guest...

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry

Background:

• Cyclodextrins (CDs) are cyclic oligosaccharides with unique host-guest properties.
• Derivatization of CDs with multicharged side chains enhances binding affinity and selectivity.
• Understanding structure-recognition relationships is crucial for designing effective CD hosts.

Purpose of the Study:

• To investigate the molecular recognition mechanisms of multicharged cyclodextrin derivatives.
• To correlate structural features of modified CDs with their binding affinities for guests.
• To provide theoretical guidance for developing novel high-affinity host molecules.

Main Methods:

• Molecular dynamics (MD) simulations were employed to study host-guest interactions.
• Umbrella sampling and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) were used for binding free energy calculations.
• Various multicharged cyclodextrin derivatives and guest molecules were computationally modeled.

Main Results:

• Glutamic acid-substituted γ-CD exhibited the strongest binding with rocuronium bromide (ROC), with a free energy of -103.1 kJ mol⁻¹.
• Electrostatic interactions were identified as the dominant force in host-guest binding.
• Synergistic contributions from hydrophobic interactions, van der Waals forces, hydrogen bonding, and geometric complementarity were observed.
• Other complexes, including edrophonium@succinic acid-substituted β-CD and simvastatin@ammonium-substituted β-CD, showed significant binding energies.

Conclusions:

• Multicharged cyclodextrin derivatives offer enhanced host-guest binding capabilities.
• Electrostatic interactions play a pivotal role in the molecular recognition of these systems.
• The study provides valuable mechanistic insights and theoretical support for designing advanced cyclodextrin-based hosts.