Recognition of monoamine neurotransmitters by cucurbiturils

[Display omitted] •Monoamine neurotransmitters complexes with CB7 were investigated using MD simulations.•MM-PBSA was used to obtain estimates of the binding free energies of the complexes.•The complexation of two dopamine analogs with CB7 was also explored.•Dopamine complexes with CB6 and CB8 were studied using MD simulations. Neurological disorders are linked to deficiencies in monoamine neurotransmitters (NTs) in the brain, and their inability to cross the blood–brain barrier (BBB) prevents their use as treatments. Encapsulating them within an appropriate host could present a potential remedy. Molecular dynamics (MD) simulations are employed to investigate the molecular recognition of protonated and neutral forms of five NTs and two dopamine (DP) analogs by cucurbit[n]urils (CBn). Binding free energies (ΔG), computed with the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, reveal CB7 forms stable inclusion complexes with all studied NTs, driven by ion–dipole/dipole–dipole interactions between and the ammonium/amine in the NT with the carbonyl portal of CB7, as well as van der Waals interactions of the included catechol/heterocyclic ring. ΔG was more favorable (by ∼2–3 kcal.mol−1) for the DP analogs. MD simulations performed to study complexation between DP and CB6 and CB8 revealed 1:1 and 2:1 stoichiometries, respectively.