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

Dopamine (DP), an essential neurotransmitter implicated in diverse brain functions, was investigated as a guest molecule within the host cavities of cucurbit[7]uril (CB7) and β-cyclodextrin (βCD) using isothermal titration calorimetry (ITC), UV-titration, ¹H NMR, molecular dynamics (MD) and density functional theory (DFT) calculations. The experimentally estimated binding constants of the 1:1 complexes of DP with CB7 and βCD were found to be 5.3 × 10⁵ and 2.7 × 10³ M^-1, respectively. ¹H NMR results further confirmed the complex formation for both hosts and provided structural insights. MD simulations revealed in the case of DP-CB7 complex a more rigid structure and deeper inclusion of the catechol moiety. Furthermore, results from the Molecular-Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) method supported the experimental affinity data, revealing the higher affinity of DP towards CB7, a result of ion-dipole interactions. DFT calculations further supported the affinity data. TD-DFT predicted for both complexes a red shift in the absorption peak of DP.