Inclusion Scenarios and Conformational Flexibility of the SSRI Paroxetine as Perceived from Polymorphism of β-Cyclodextrin–Paroxetine Complex

Depression, a global mental health problem, is prevalent during the coronavirus disease 2019 (COVID-19) pandemic and can be efficiently treated by selective serotonin reuptake inhibitors (SSRIs). Our study series aims at forwarding insights on the β-cyclodextrin (β-CD)–SSRI inclusion complexes by X-ray crystallography combined with density functional theory (DFT) calculation. Here, we report a new crystal form (II) of the 1:1 β-CD–paroxetine (PXT) complex, which is inspired by the reported 2:1 β-CD–PXT complex (crystal form I), reflecting an elusive phenomenon of the polymorphism in CD inclusion complexes. The β-CD–PXT polymorphism stems from the PXT conformational flexibility, which is defined by torsion angles κ, ε around the -CH2–O- group bridging the A- and C–D-rings, of which those of PXT in I and II are totally different. While PXT (II) in an open V-shaped conformation that has the B-ring shallowly inserted in the β-CD cavity, PXT (I) in a closed U-shaped structure is mostly entirely embedded in the β-CD dimeric cavity, of which the A-ring is deeply inserted in the main β-CD cavity. However, PXT molecules in both crystal forms are similarly maintained in the CD cavity via host–guest N–H···O5/O6 H-bonds and C/O–H···π(B/C) interactions and β-CDs have similar 3D arrangements, channel (II) vs. screw-channel (I). Further theoretical explorations on the β-CD–PXT thermodynamic stabilities and the PXT conformational stabilities based on their potential energy surfaces (PESs) have been completed by DFT calculations. The 2:1 β-CD–PXT complex with the greater presence of dispersion interactions is more energetically favorable than the unimolar complex. Conversely, whereas free PXT, PXT (II) and PXT in complex with serotonin transporter are more energetically stable, PXT (I) is least stable and stabilized in the β-CD cavity. As SSRIs could lessen the COVID-19 severity, the CD inclusion complexation not only helps to improve the drug bioavailability, but also promotes the use of antidepressants and COVID-19 medicines concurrently.

Development of Inclusion Complexes With Relative Humidity Responsive Capacity as Novel Antifungal Agents for Active Food Packaging

Background: Allyl isothiocyanate is an excellent antimicrobial compound that has been applied in the development of active food packaging materials in the last years. However, the high volatility of this compound could prevent a lasting effect over time. In order to avoid this problem, cyclodextrin inclusion complexes have been proposed as an alternative, being beta-cyclodextrin (β-CD) as the main candidate. In addition, β-CD could act as a relative humidity-responsive nanoparticle. In this regard, the aim of this study was to develop inclusion complexes based on β-CD and AITC as relative humidity-responsive agents, which can be used in the design of active food packaging materials.Methods: Two different β-CD:AITC inclusion complexes (2:1 and 1:1 molar ratios) were obtained by the co-precipitation method. Entrapment efficiency was determined by gas chromatography, while inclusion complexes were characterized through thermal, structural, and physicochemical techniques. Antifungal capacity of inclusion complexes was determined in a headspace system. Furthermore, the AITC release from inclusion complexes to headspace at different percentages of relative humidity was evaluated by gas chromatography, and this behavior was related with molecular dynamic studies.Key Findings and Conclusions: The entrapment efficiency of inclusion complexes was over to 60%. Two coexisting structures were proposed for inclusion complexes through spectroscopic analyses and molecular dynamic simulation. The water sorption capacity of inclusion complexes depended on relative humidity, and they exhibited a strong fungicide activity against Botrytis cinerea. Furthermore, the AITC release to headspace occurred in three stages, which were related with changes in β-CD conformational structure by water sorption and the presence of the different coexisting structures. In addition, a strong influence of relative humidity on AITC release was evidenced. These findings demonstrate that β-CD:AITC inclusion complexes could be used as potential antifungal agents for the design of food packaging materials, whose activity would be able to respond to relative humidity changes.

Host-guest stoichiometry affects the physicochemical properties and releases kinetics of beta-cyclodextrin/ ferulic acid inclusion complexes

An inclusion system of embedding ferulic acid into β-cyclodextrin (FACD) with different host-guest stoichiometry was prepared by a co-precipitation method. Then, the physicochemical properties and release kinetics of the FACD...

Pickering emulgels reinforced with host-guest supramolecular inclusion complexes for high fidelity direct ink writing

Direct ink writing (DIW) of Pickering emulsions offers great potential for constructing on-demand objects. However, the rheological properties of fluid emulsions greatly undermines the shape fidelity and structural integrity of...