betadex and 1-6-hexamethylene-diisocyanate

Derivatized β-cyclodextrins (CDs), cyclic oligomers of glucose with inner cavity, are able to form the inclusion complex with many poorly soluble lipophilic organic molecules, including drugs, thus improving their solubility in aqueous solutions and drug bioavailability. Here, we have studied the effect of cross-linking of derivatized CDs with different substituent nature, on their binding with antibacterial drug moxifloxacin (MF) which served as a model small molecule drug. Cross-linking of derivatized CDs with 1,6-hexamethylene diisocyanate (HMD) yielded 100-200 nm nanoparticles with distinct binding properties, strongly depending on the nature of the CD substituent, degree of oligomerization, and the nanoparticle's charge. Interestingly, substituent that improved MF binding to monomeric CDs the most (methyl moiety), had reverse effect in the case of cross-linked CD. Whereas the substituent that had only limited effect on the monomeric CD (sulfobutyl ether moiety), improved binding of cross-linked CD by almost two orders of magnitude. Further, we show that the cross-linked CD complexes with MF perform better in vitro antibacterial assay on E.coli, compared to both free MF and monomeric CD-MF. Overall, this data indicates the potential utility of CD cross-linking and derivatization to develop small molecule drug formulations with improved pharmacological properties.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Escherichia coli; Isocyanates; Moxifloxacin

Here we report the use of β-cyclodextrin polyurethane nanosponges cross-linked with 1,6-hexamethylene diisocyanate as a template for the preparation of Aun quantum clusters, by the core-etching of glutathione-capped Au nanoparticles. The study of temporal evolution of the core-etching process using different Au concentrations indicated that formation of Aun clusters embedded in the nanosponge is favored by the use of lower Au concentrations, since it began at shorter times and lead to higher cluster loading. An estimation of the number of Au atoms based on the maximum photoluminescence wavelength suggested that, depending on the Au concentration and the core etching time, clusters with 11-15 atoms were formed. After excluding the possibility of an inclusion complex formation, evaluation of the catalytic activity of nanosponge-loaded Aun clusters toward the reduction of 4-nitrophenol has shown that the reaction is catalyzed by the Aun clusters with no induction time, following the Langmuir-Hinshelwood kinetic model.

Topics: beta-Cyclodextrins; Catalysis; Glutathione; Gold; Isocyanates; Models, Molecular; Molecular Conformation; Nitrophenols; Oxidation-Reduction; Polyurethanes; Quantum Dots

A urethane-based polymer material, denoted HDI-1, was obtained from the addition reaction of β-cyclodextrin (β-CD) with 1,6-hexamethylene diisocyanate (HDI) at the 1:1 mole ratio. In aqueous solution and ambient temperature conditions, HDI-1 adopts a compact (coiled) morphology where the cross-linker units become coiled and are partially self-included in the annular hydroxyl (interstitial) region of β-CD. As the temperature is raised or as p-nitrophenol (PNP) was included within the β-CD cavity and the noninclusion sites of the polymer, an extended (uncoiled) morphology was adopted. The equilibrium distribution between the extended and the compact forms of HDI-1 is thermally and chemically switchable, in accordance with the hydration properties and host-guest chemistry of this responsive polymer system. The molecular structure of this water-soluble urethane polymer and its host-guest complexes with PNP were investigated using spectroscopic (Raman, (1)H NMR, induced circular dichroism), dynamic light scattering (DLS), and calorimetric (DSC) methods in aqueous solution at ambient pH, and compared with native β-CD. This study reports on the unique supramolecular properties of a polymer that resembles a thermally and chemically responsive "molecular accordion".

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Circular Dichroism; Dynamic Light Scattering; Isocyanates; Molecular Conformation; Polyurethanes; Proton Magnetic Resonance Spectroscopy; Spectrum Analysis, Raman; Temperature

The processes of molecular-imprinting of beta-cyclodextrin (beta-CyD) with cholesterol and stigmasterol (cross-linking agent = diisocyanate) have been analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. These templates enormously promote the formation of dimers and trimers of beta-CyD, which are only inefficiently formed in their absence. These ordered assemblies are the guest-binding sites, in which two or three beta-CyD molecules cooperate to bind large steroids. Ordered assemblies are also formed when 2,6-di-O-methyl-beta-cyclodextrin is used in place of beta-CyD. Direct spectroscopic evidence for molecular-imprinting effect has been obtained. Molecular imprinting of CyDs is potent for tailor-made preparation of synthetic receptors for nanometer-scaled guests.

Topics: beta-Cyclodextrins; Cholesterol; Cross-Linking Reagents; Cyanates; Cyclodextrins; Isocyanates; Magnetic Resonance Spectroscopy; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stigmasterol; Templates, Genetic; Toluene 2,4-Diisocyanate