Cucurbit[7]uril and β-cyclodextrin as hosts for dopamine: complexation, affinity, and computational insights.

Area of Science:

• Supramolecular Chemistry
• Neuroscience
• Computational Chemistry

Background:

• Dopamine (DP) is a crucial neurotransmitter involved in various brain functions.
• Host-guest chemistry explores the interactions between molecules within confined spaces.
• Cucurbit[7]uril (CB7) and β-cyclodextrin (βCD) are macrocyclic hosts with potential for molecular recognition.

Purpose of the Study:

• To investigate the complexation of dopamine (DP) with cucurbit[7]uril (CB7) and β-cyclodextrin (βCD).
• To determine the binding affinities and structural characteristics of DP-CB7 and DP-βCD complexes.
• To elucidate the driving forces behind the host-guest interactions using computational methods.

Main Methods:

• Isothermal titration calorimetry (ITC) and UV-titration for binding affinity determination.
• Proton Nuclear Magnetic Resonance (¹H NMR) for complex formation and structural insights.
• Molecular dynamics (MD) simulations, MM-PBSA, and Density Functional Theory (DFT) calculations for structural and energetic analysis.

Main Results:

• Experimentally determined binding constants showed significantly higher affinity of DP for CB7 (5.3 × 10⁵ M⁻¹) compared to βCD (2.7 × 10³ M⁻¹).
• ¹H NMR confirmed complex formation and provided structural details for both host-guest systems.
• MD simulations indicated a more rigid DP-CB7 complex with deeper inclusion of the catechol moiety.
• Computational methods (MM-PBSA, DFT) supported the experimental findings, highlighting ion-dipole interactions as key for DP-CB7 affinity.
• TD-DFT predicted a red shift in the absorption peak of DP upon complexation with both hosts.

Conclusions:

• Dopamine exhibits a strong preference for complexation with cucurbit[7]uril over β-cyclodextrin.
• The enhanced binding affinity towards CB7 is attributed to favorable ion-dipole interactions and structural factors.
• Computational modeling provides valuable insights into the structural and energetic aspects of host-guest complexation, complementing experimental data.