Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various ß-cyclodextrin derivatives using advanced computational techniques and experimental validation.

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with ß-cyclodextrin (ßCD) and its three analogs, dimethyl-ß-cyclodextrin (DMßCD), hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4',6'-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with ßCDs through two distinct orientations, with OXY/SBEßCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEßCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEßCD (2060 M-1), HPßCD (1860 M-1), DMßCD (1700 M-1), and ßCD (1420 M-1). All complexes exhibited a 1:1 binding mode (AL type), with SBEßCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMßCD, OXY/HPßCD, and OXY/SBEßCD were markedly superior compared to that of OXY alone.

Switchable Metal-Ion Selectivity in Sulfur-Functionalised Pillar[5]arenes and Their Host-Guest Complexes.

Nucleophilic substitution of pertosylated pillar[5]arene (P-OTs) with commercially available sulfur containing nucleophiles (KSCN, KSAc, and thiophenol), yields a series of sulfur-functionalised pillar[5]arenes. DLS results and SEM images imply that these pillararene macrocycles self-assemble in acetonitrile solution, while X-ray crystallographic evidence suggests solvent-dependent assembly in the solid state. The nature of the sulfur substituents decorating the rim of the pillararene controls binding affinities towards organic guest encapsulations within the cavity and dictates metal-ion binding properties through the formation of favorable S-M2+ coordination bonds outside the cavity, as determined by 1 H NMR and fluorescence spectroscopic experiments. Addition of a dinitrile guest containing a bis-triazole benzene spacer (btn) induced formation of pseudorotaxane host-guest complexes. Fluorescence emission signals from these discrete macrocycles were significantly attenuated in the presence of either Hg2+ or Cu2+ in solution. Analogous titrations utilizing the corresponding pseudorotaxanes alter the binding selectivity and improve fluorescence sensing sensitivity. In addition, preliminary liquid-liquid extraction studies indicate that the macrocycles facilitate the transfer of Cu2+ from the aqueous to the organic phase in comparison to extraction without pillar[5]arene ligands.