Hwanhee Kim

Functionalized β-cyclodextrin as supramolecular ligand and their Pd(OAc)2 complex: highly efficient and reusable catalyst for Mizoroki–Heck cross-coupling reactions in aqueous medium

A novel class of water soluble palladium complexes with recognition abilities based on functionalized β-cyclodextrin has been synthesized. The complex demonstrated high catalytic activity and a supramolecular platform for phosphine-free Mizoroki-Heck cross-coupling reactions in water. The efficient arylation of alkenes was carried out using different iodo- and bromo-arenes with good to excellent yields (up to 96%). The advantages, like recyclability of catalysts, operational simplicity and accessibility in aqueous medium, make this protocol eco-friendly.

Novel magnetic nanoparticles coated by benzene- and β-cyclodextrin-bearing dextran, and the sorption of polycyclic aromatic hydrocarbon.

We present the synthesis of novel magnetic nanoparticles functionalized by benzene- and β-cyclodextrin-derivatized dextran. The grafting strategy was based on the [alkynyl-iron] cluster in the modified dextrans, which were prepared by click reaction from alkyne-modified dextran and benzyl azide or mono-6-O-deoxy-monoazido β-cyclodextrin. Characterization was then carried out by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. Using the developed magnetic nanoparticles, the potential for removing polycyclic aromatic hydrocarbons such as phenanthrene and pyrene by sorption onto the nanomaterials was assessed. In the sorption, pi-stacking interactions of the benzene-derivatized dextran and host-guest chemistry of the β-cyclodextrin-derivatized dextran were considered to be significant. Furthermore, the polysaccharide derivative-coated magnetic adsorbents could be recovered by an external magnet for reuse.

Removal of methyl violet dye by adsorption onto N-benzyltriazole derivatized dextran

In this work, N-benzyltriazole derivatized dextran was evaluated for its potential as a novel carbohydrate-based adsorbent for the removal of methyl violet dye from water. The modified dextran was synthesized by a click reaction of pentynyl dextran and benzyl azide, and the structure was characterized by nuclear magnetic resonance spectroscopy, elemental analysis, and scanning electron microscopy. Dextran was substituted with a triazole-linked benzyl group. For decolorization of the dye effluent, adsorption is a very effective treatment; here, the driving force is based on hydrogen bonding, pi stacking, and electrostatic interaction between the methyl violet dye and the N-benzyltriazole derivatized dextran. Batch experiments were carried out to investigate the required contact time and the effects of pH, initial dye concentrations, and temperature. The experimental data were analyzed with equilibrium isotherms including the Langmuir, Freundlich, and Temkin models. Based on the Langmuir isotherm, the maximum adsorption capacity was determined to be 95.24 mg of dye per gram of the adsorbent. The adsorption obeyed pseudo-second order kinetics, and a negative ΔG0 value indicated adsorption spontaneous in nature.

Supramolecular self-assembled aggregates formed by pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin

Mono[6-deoxy-6-(pentacosa-10,12-diynyl amidomethyl)]-β-cyclodextrin was successfully synthesized by reacting mono-6-amino-6-deoxy-β-cyclodextrin with N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid in DMF. The modified β-cyclodextrin self-assembled and aggregated to form a worm-like supramolecular structure, and the novel supramolecular aggregates were studied using 2D nuclear magnetic resonance spectroscopy, X-ray powder diffraction, thermogravimetry, and electron microscopy. Interestingly, the synthesized pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin formed columnar type self-aggregates and it was clearly differentiated from cage-like structure of native β-cyclodextrin.

Intermolecular complexation of low-molecular-weight succinoglycans directs solubility enhancement of pindolol

The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are repeating octasaccharide units consisting of monomers, dimers, and trimers. Pindolol is a beta-blocker used to treat cardiovascular disorders. We investigated the formation of complexes between pindolol and low-molecular-weight succinoglycan monomers (SGs). Even though SGs have a linear structure, the solubility of pindolol in the presence of SGs was increased up to 7-fold compared with methyl-β-cyclodextrin reported as the best solubilizer of pindolol. Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Formation constants of complexes were determined from phase solubility diagrams. Conformation of complex was suggested based on a molecular docking study. The present study indicated that formation of pindolol/SGs complexes not only resulted in increased pindolol solubility but also could be useful for improving its clinical application as it did not affect cell viability.

β-CD Dimer-immobilized Ag Assembly Embedded Silica Nanoparticles for Sensitive Detection of Polycyclic Aromatic Hydrocarbons.

We designed a β-CD dimer on silver nanoparticles embedded with silica nanoparticles (Ag@SiO2 NPs) structure to detect polycyclic aromatic hydrocarbons (PAHs). Silica NPs were utilized as a template for embedding silver NPs to create hot spot structures and enhance the surface-enhanced Raman scattering (SERS) signal, and a thioether-bridged dimeric β-CD was immobilized on Ag NPs to capture PAHs. The assembled Ag NPs on silica NPs were confirmed by TEM and the presence of β-CD dimer on Ag@SiO2 was confirmed by UV-vis and attenuated total reflection-Fourier transform infrared spectroscopy. The β-CD dimer@Ag@SiO2 NPs were used as SERS substrate for detecting perylene, a PAH, directly and in a wide linearity range of 10−7 M to 10−2 M with a low detection limit of 10−8 M. Also, the β-CD dimer@Ag@SiO2 NPs exhibited 1000-fold greater sensitivity than Ag@SiO2 NPs in terms of their perylene detection limit. Furthermore, we demonstrated the possibility of detecting various PAH compounds using the β-CD dimer@Ag@SiO2 NPs as a multiplex detection tool. Various PAH compounds with the NPs exhibited their distinct SERS bands by the ratio of each PAHs. This approach of utilizing the assembled structure and the ligands to recognize target has potential for use in sensitive analytical sensors.

Solubilization of haloperidol by acyclic succinoglycan oligosaccharides.

The isolated succinoglycan octasaccharide dimers isolated from Sinorhizobium meliloti 1021 have unique acyclic structures, displaying amphipathic properties against water. Thus, their potential usage as solubilizers of various water-insoluble drugs through non-covalent complexation are possible. In this study, we examined the solubility of a poorly water-soluble drug, haloperidol, in the presence of the acyclic form of succinoglycan dimers, and demonstrated that its solubility was increased up to 87 fold, Interestingly, the level of its solubility was even 7-10 fold higher than that achieved with β cyclodextrin or its derivatives that are cyclic forms, which is possibly due to the molecular flexibility of the acyclic structure of the dimers as well as the hydrophobic nature. Analyses of the stoichiometry and the stability constants for each complex were performed using phase solubility method, respectively. Additional analyses were also performed to confirm the formation of succinoglycan-drug complexes. Furthermore hypothetical 3-dimesional conformation of the complex was estimated through molecular docking simulations. Upon cytotoxicity test with a human cell line, the succinoglycan dimers displayed little effect up to 1000 μM, suggesting their potential usage to improve solubility and bioavailability of poorly soluble therapeutic agents.

Polydiacetylenyl β-cyclodextrin based smart vesicles for colorimetric assay of arginine and lysine

Selective visualization of arginine and lysine has been explored among 20 amino acids using the hybrid conjugate of β-cyclodextrin (β-CD) and polydiacetylene (PDA). The mono pentacosa-10,12-diynyl aminomethyl group was successfully coupled to either the primary or the secondary face of β-CD, where mono-6-amino-6-deoxy-β-CD or mono-3-amino-3-deoxy-β-CD reacted with the N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid. In this combinatorial system, the cylindrical β-cyclodextrin functions as a channel for the introduction of the cationic amino acids to the artificial membrane. The membrane perturbation and aggregation by the target amino acids could be exclusively visualized as a blue to red color change based on the responsive polydiacetylene domain. These interesting findings demonstrated that the developed β-CD conjugated PDA system may offer a new method of cell-penetrating mechanism, a promising vector system, as well as impact the production industry of arginine or lysine.

Characterization and Enhanced Antioxidant Activity of the Cysteinyl β-Cyclodextrin-Baicalein Inclusion Complex.

Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The present study aimed to prepare and characterize a host-guest complex in an effort to improve the solubility and antioxidant activity of baicalein. The host molecule is a macrocyclic β-cyclodextrin (β-CD) functionalized with cysteine for a synergetic effect. The structure of the synthesized cysteinyl β-CD was analyzed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The inclusion complex with baicalein was studied by UV-vis, NMR spectroscopy, scanning electron microscopy, and X-ray powder diffractometry. The formed cysteinyl β-CD/baicalein inclusion complex efficiently improved the solubility and antioxidant ability of baicalein. Therefore, we suggest that the present cysteinyl β-CD is a potential host molecule for inclusion complexation and for bioavailability augmentation.

Carboxymethyl cyclosophoraoses as a flexible pH-responsive solubilizer for pindolol

In the present study, cyclosophoraoses (CyS) (β-1,2 linked cyclic glucans, with glucopyranose units ranging from 17 to 23) isolated from Rhizobium leguminosarum biovar viciae VF-39 were modified with carboxymethyl (CM) groups, and the pH-sensitive complexation of CM CyS with pindolol was investigated. The solubility of pindolol increased 32-fold by its complexation with 5mM CM CyS at pH 10, whereas it shows no significant change at pH 3. Pindolol, a β-adrenergic blocking agent, has a hydrophobic nature at non-ionized state, and CM CyS could solubilize efficiently pindolol in a high alkaline solution. The carboxymethylation of flexible CyS allows them to present a more suitable cavity for the hydrophobic pindolol at pH 10, which is differentiated from CM β-cyclodextrin (β-CD). It can be interpreted as that the anionic repulsion effectively modulates the flexible and distorted conformation of CyS rather than rigid annular shape of β-CD. Resultingly, the highly solubilized CM CyS/pindolol complex was characterized by UV-vis, T1 relaxation, ROESY, DOSY NMR spectroscopy, FT-IR spectroscopy, SEM, and molecular modeling studies. The antioxidant activity of pindolol was also improved 260% in the complex compared to free pindolol. The use of flexible host molecules with pH-responsive substituents would be applied in the development of smart systems for sensing or in biomedical fields.