Sangyeul Hwang

Spontaneous shape reconfigurations in multicompartmental microcylinders

Nature’s particles, such as spores, viruses or cells, are adaptive—i.e., they can rapidly alter major phenomenological attributes such as shape, size, or curvature in response to environmental changes. Prominent examples include the hydration-mediated opening of ice plant seeds, actuation of pine cones, or the ingenious snapping mechanism of predatory Venus flytraps that rely on concave-to-convex reconfigurations. In contrast, experimental realization of reconfigurable synthetic microparticles has been extremely challenging and only very few examples have been reported so far. Here, we demonstrate a generic approach towards dynamically reconfigurable microparticles that explores unique anisotropic particle architectures, rather than direct synthesis of sophisticated materials such as shape-memory polymers. Solely enabled by their architecture, multicompartmental microcylinders made of conventional polymers underwent active reconfiguration including shape-shifting, reversible switching, or three-way toggling. Once microcylinders with appropriate multicompartmental architectures were prepared by electrohydrodynamic cojetting, simple exposure to an external stimulus, such as ultrasound or an appropriate solvent, gives rise to interfacial stresses that ultimately cause reversible topographical reconfiguration. The broad versatility of the electrohydrodynamic cojetting process with respect to materials selection and processing suggests strategies for a wide range of dynamically reconfigurable adaptive materials including those with prospective applications for sensors, reprogrammable microactuators, or targeted drug delivery.

Polyurethane with tethered copper(II)–cyclen complex: Preparation, characterization and catalytic generation of nitric oxide from S-nitrosothiols

The preparation and characterization of a commercial biomedical-grade polyurethane (Tecophilic((R)), SP-93A-100) material possessing covalently linked copper(II)-cyclen moieties as a nitric oxide (NO) generating polymer are described. Chemiluminescence NO measurements demonstrate that the prepared polymer can decompose endogenous S-nitrosothiols (RSNOs) such as S-nitrosoglutathione and S-nitrosocysteine to NO in the presence of thiol reducing agents (RSHs; e.g., glutathione and cysteine) at physiological pH. Since such RSNO and RSH species already exist in blood, the proposed polymer is capable of spontaneously generating NO when in contact with fresh blood. This is demonstrated by utilizing the polymer as an outer coating at the distal end of an amperometric NO sensor to create a device that generates response toward the RSNO species in the blood. This polymer possesses the combined benefits of a commercial biomedical-grade polyurethane with the ability to generate biologically active NO when in contact with blood, and thus may serve as a useful coating to improve the hemocompatibility of various medical devices.

Differentially Degradable Janus Particles for Controlled Release Applications

Janus particles with differentially degradable compartments were prepared by electrohydrodynamic (EHD) co-jetting and subsequent controlled crosslinking. These bicompartmental particles are composed of an interpenetrating polymer network of poly(ethylene oxide) and poly(acrylamide-co-acrylic acid) in one hemisphere and a crosslinked copolymer of dextran and poly(acrylamide-co-acrylic acid) segments in the second compartment. The compositional anisotropy caused differential hydrolytic susceptibility: Although both compartments were stable at pH 3.0, selective degradation of the PEO-containing compartment pH 7.4 was observed within 5 days. Janus particles with differentially degradable polymer compartments may be of interest for a range of oral drug delivery applications because of their propensity for decoupled release profiles.

Anisotropic Janus Catalysts for Spatially Controlled Chemical Reactions

catalyst toriously ay may catalytic ompartcolloidal building blocks. [ 1–6 ] In the last decade, sev entifi c advances led to the preparation of a diverse anisotropic particles including particles with differen patchy particles, and compartmentalized particles emerging bulk of research has been focused on the tion of multicompartmentalized polymer microand n ticles. [ 6–11 ] Compared to particles with anisotropic dis of surface patches, multicompartmentalized partic have several additional properties, such as anisotrop dation or spatially controlled swelling/deswelling w same particle. [ 6–8 , 12 , 13 ] Some of the potentially most p applications may involve anisotropic catalysts that ca spatially separated chemical reactions. [ 12 ] As desc Crossley et al., Janus catalysts could control chemi tions at the interface of oil and water, which enhances activity relative to homogenous catalysts, while fa simple catalyst recovery. [ 12 ] Anisotropic catalyst parti

Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor

Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.

Compartmentalization of Gold Nanocrystals in Polymer Microparticles using Electrohydrodynamic Co-Jetting

Polymer particles with micro- and nanoscale anisotropy have received increasing interest for their ability to simultaneously present different physical- and chemical properties. In this communication, we demonstrate that gold nanocrystals (NCs) can be selectively incorporated into one compartment of anisotropic polymer particles. Stable bicompartmental particles were prepared via electrohydrodynamic co-jetting of aqueous nanoparticle suspensions followed by thermal cross-linking. Bicompartmental particle populations with different NC densities were obtained by varying the NC concentration in the jetting suspension. While NC-loaded polymer particles showed different optical properties depending on the NC density, they still maintained discrete interfaces between two compartments. Moreover, the fraction of the bicompartmental particles was higher than 98% based on flow cytometry. This study delineates a new approach for preparation of inorganic/organic composite particles with precisely engineered, anisotropic nanoparticle distributions and may contribute to further developments in emerging scientific areas, such as smart materials or particle-based diagnostics.

STRUCTURAL MODIFICATION OF AN ORALLY ACTIVE THROMBIN INHIBITOR, LB30057: REPLACEMENT OF THE D-POCKET-BINDING NAPHTHYL MOIETY

An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (Ki = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (Ki = 0.045 nM).

Rational design of selective thrombin inhibitors

Abstract Thrombin inhibitors with functionalized benzamidines as surrogates for arginine were designed, synthesized, and characterized. Amino acid sequence difference in the position 190 between thrombin and trypsin was exploited in the design to enhance selectivity over trypsin. A representative compound 6 showed high potency (Ki of 45.5 nM) and extremely high specificity over trypsin (over 10,000 fold).

Compartmentalized Photoreactions within Compositionally Anisotropic Janus Microstructures

We demonstrate spatially controlled photoreactions within bicompartmental microparticles and microfibers. Selective photoreactions are achieved by anisotropic incorporation of photocrosslinkable poly(vinyl cinnamate) in one compartment of either colloids or microfibers. Prior to photoreaction, bicompartmental particles, and fibers were prepared by EHD co-jetting of two compositionally distinct polymer solutions. Physical and chemical anisotropy was confirmed by confocal laser scanning microscopy, Fourier-transformed infrared spectroscopy, and scanning electron microscopy. The data indicate adjustment of polymer concentrations of the jetting solutions to be the determining factors for particle and fiber structures. Subsequent exposure of poly(vinyl cinnamate)-based particles and fibers to UV light at 254 nm resulted in spatially controlled crosslinking. Treatment of the crosslinked bicompartmental colloids with chloroform produced half-moon shaped objects. These hemishells exhibited a distinct porous morphology with pore sizes in the range of 70 nm. Based on this novel synthetic approach, Janus-type particles and fibers can be prepared by EHD co-jetting and can be selectively photocrosslinked without the need for masks or selective laser writing.

Organoditelluride-mediated catalytic S-nitrosothiol decomposition

An organoditelluride (5,5′-ditelluro-2,2′-dithiophenecarboxylic acid) and a polymeric derivative thereof are shown to exhibit catalytic decomposition of S-nitrosothiols such as S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CySNO).