Supramolecular Encapsulation of a Neurotransmitter Serotonin by Cucurbit[7]uril

Abstract

pH-dependent host-guest complexation of a monoamine neurotransmitter, Serotonin, with cucurbit[7]uril has been thoroughly investigated. The binding phenomena were explored using steady-state and time-resolved fluorescence spectroscopy at different pH values. At lower pH, i.e., protonated Serotonin, the binding affinity with cucurbit[7]uril was significantly higher compared to higher pH. Furthermore, detailed NMR titration experiments depicted the solution structure of the host-guest complex through the complexation induced chemical shift values. A competitive binding assay with cesium ions at pD 2.8 was subsequently performed for the further manifestation of the binding. Finally, the molecular docking studies provided well-documented proof of the 1:1 inclusion complex and the geometry of the complex. We believe that understanding from such studies can be important for pH-controlled delivery of serotonin for biological applications.

Assessment of the Biocompatibility of Cucurbiturils in Blood Cells

“…Cyclodextrin has been reported to induce shape changes of the membrane internalization type on erythrocytes. CyDs can release cholesterol from the erythrocyte membrane, thereby causing hemolysis [13]. It is known that CB [7] and other homologues (with the exception of CB [5] and CB [6]) can also bind cholesterol molecules [31], so the hemolytic effect of cucurbiturils may be similar to the effects of cyclodextrins.…”

“…These data assert and allow using cucurbiturils as a remarkable drug delivery system. Special cases of the encapsulation by cucurbiturils of serotonin [13] and histamine H2 antagonists such as cimetidine, famotidine and nizatidine [14] in the 1:1 inclusion complex allow to expand the possibility of cucurbituril's application for various nosologies. Recently, it was reported that complexation CB [7] with chloroquine permits reducing its nonspecific toxicity over several rounds and improves its antiviral activity against coronavirus, confirming the pronounced synergistic effect of cucurbiturils.…”

Host–guest complexation between cucurbit[7]uril and doxepin induced supramolecular assembly

“…27 Recently, the complexation of serotonin, a neurotransmitter, with CB7 has been reported. 28 The results indicated that CB7 forms a 1 : 1 inclusion complex with serotonin with a binding affinity of 2.3 × 10 4 M −1 .…”

“…E-mail: Khaleel.assaf@bau.edu.jo reported. 28 The results indicated that CB7 forms a 1 : 1 inclusion complex with serotonin with a binding affinity of 2.3 × 10 4 M −1 .…”

Cucurbit[7]uril Nanoencapsulation Reduces the Unpalatability of Bitter Phytochemicals

“…A desirable attribute of any supramolecular encapsulation mechanism is that the activity of the molecule being delivered should not be adversely affected because of administration through the delivery vehicle. The activity of various drugs delivered through supramolecular encapsulation in cucurbiturils has been found to have remained unchanged, showing that cucurbit­[ n ]­urils can act as efficient encapsulation and delivery agents. − Recently, cucurbit[7]­uril (or CB7) (Figure ) has been used to conceal the bitter taste of denatonium benzoate, known to be the most bitter compound to humans, and has been evaluated in mice, where it was found that CB7 encapsulation can abolish the aversive response toward denatonium benzoate . Hence, we selected CB7 as a candidate macrocycle for the nanoencapsulation of bitter phytochemicals to be introduced into an insect model system.…”