Particle size effect in the mechanically assisted synthesis of ß-cyclodextrin mesitylene sulfonate

Mechanically assisted synthesis of organic compounds has recently focused considerable attention as it may be unique in features to selectively orient the reaction pathway. In the continuation of our work on the synthesis of modified cyclodextrins (CDs) via mechanochemical activation, we sought to discriminate the contribution of supramolecular effects and grinding during the course of a reaction in the solid state. As such, we recently investigated the influence of the particles size of β-CD in the synthesis of β-CD mesitylene sulfonate (β-CDMts) in the solid state using a vibrating ball-mill. We were particularly interested in the role of the particles size on the kinetics of the reaction. In this study, we show that grinding β-CD reduces the particles size over time down to a limit of 167 nm. The granulometric composition remains rather invariant for grinding times over 1 h. Each type of β-CD particles reacted with mesitylene sulfonic chloride (MtsCl) to produce β-CDMts. Contrary to what could be intuitively anticipated, smaller particles did not lead to the highest conversions. The impact of grinding over the conversions was limited. Interestingly, the proportion of β-CDMts mono-substituted on the primary face significantly increased over time when the reaction was carried out in the presence of KOH as a base. The data series were confronted with kinetics models to get clues on the way the reactions proceeded. The diversity of possible models suggests that multiple mechanochemical processes can account for the syntheses of β-CDMts in the solid state. Throughout this study, we found that the reactivity depends more upon diffusion phenomena in the crystalline parts of the material than upon the increase in the surface area of the CD particles resulting from grinding.

Modified cyclodextrins solubilize elemental sulfur in water and enable biological sulfane sulfur delivery

Sulfane sulfur, or S0, is found in polysulfide and persulfide compounds in biology. We demonstrate that modified cyclodextrins can solubilize S8 in water, increase its reactivity with biological nucleophiles, and enable delivery to live cells.

Modified cyclodextrins as broad-spectrum antivirals

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

Effects of Temperature and Host Concentration on the Supramolecular Enantiodifferentiating [4 + 4] Photodimerization of 2-Anthracenecarboxylate through Triplet-Triplet Annihilation Catalyzed by Pt-Modified Cyclodextrins

Visible-light-driven photocatalytic supramolecular enantiodifferentiating dimerization of 2-anthracenecarboxylic acid (AC) through triplet-triplet annihilation (TTA), mediated by the Schiff base Pt(II) complex (Pt-1, Pt-2, and Pt-3) was studied. The host concentration and the temperature effects on the stereoselectivity were comprehensively investigated. Increasing the concentration of sensitizers/hosts significantly enhanced the conversion of the photoreaction but led to reduced enantioselectivities of the chiral photodimers 2 and 3 when the photoreaction was triggered by a 532 nm laser, which was in contrast with the results obtained by direct irradiation of AC with a 365 nm light-emitting diode (LED) lamp, due to the aggregation of the sensitizer/host in water. The cyclization of AC through triplet-triplet annihilation displayed significant temperature dependency when Pt-3 was employed as the sensitizer/host. Increasing the temperature from 0 °C to 30 °C with 5% equiv. of Pt-3 led to a great increase of the ee of 2 from 2.1% to 31.6%. However, hardly any temperature dependency was observed when the photodimerization was mediated by other sensitizers and/or hosts, or the photoreaction was triggered directly with a 365 nm LED lamp.

Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient

The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.

Physicochemical Characterization of Febuxostat Microcomplexes with Parent and Modified Cyclodextrins

Febuxostat, a BCS class II antigout drug was complexed with β-cyclodextrin (βCD), hydroxypropyl-β- cyclodextrin (HPβCD) and / or methyl-β-cyclodextrin (MβCD), to improve its physicochemical properties. Earlier phase solubility and thermodynamic investigations in acetate buffer (pH 4.5) illustrated AL (linear) type of solubility curve and enthalpy driven complexation process, respectively. The association constant and complexation efficiency of modified cyclodextrins (CDs) were significantly higher than that of parent cyclodextrin (CD). The microcomplexes prepared by spray drying process were examined for their spectral, diffractometric, thermal, particle size, saturation solubility, Log P and dissolution properties. The physicochemical properties of pure drug were improved upon complexation with CDs. However, modified CDs produced amorphous micro-complexes contributing for their better performance as compared to parent CD.Dhaka Univ. J. Pharm. Sci. 17(1): 51-63, 2018 (June)