Yuta Koda

Sequence-Regulated Copolymers via Tandem Catalysis of Living Radical Polymerization and In Situ Transesterification

Sequence regulation of monomers is undoubtedly a challenging issue as an ultimate goal in polymer science. To efficiently produce sequence-controlled copolymers, we herein developed the versatile tandem catalysis, which concurrently and/or sequentially involved ruthenium-catalyzed living radical polymerization and in situ transesterification of methacrylates (monomers: RMA) with metal alkoxides (catalysts) and alcohols (ROH). Typically, gradient copolymers were directly obtained from the synchronization of the two reactions: the instantaneous monomer composition in feed gradually changed via the transesterification of R(1)MA into R(2)MA in the presence of R(2)OH during living polymerization to give R(1)MA/R(2)MA gradient copolymers. The gradient sequence of monomers along a chain was catalytically controlled by the reaction conditions such as temperature, concentration and/or species of catalysts, alcohols, and monomers. The sequence regulation of multimonomer units was also successfully achieved in one-pot by monomer-selective transesterification in concurrent tandem catalysis and iterative tandem catalysis, providing random-gradient copolymers and gradient-block counterparts, respectively. In contrast, sequential tandem catalysis via the variable initiation of either polymerization or in situ transesterification led to random or block copolymers. Due to the versatile adaptability of common and commercially available reagents (monomers, alcohols, catalysts), this tandem catalysis is one of the most efficient, convenient, and powerful tools to design tailor-made sequence-regulated copolymers.

Arm-Cleavable Microgel Star Polymers: A Versatile Strategy for Direct Core Analysis and Functionalization

Arm-cleavable microgel star polymers were developed, where the arm chains can readily be cleaved by acidolysis after the synthesis, allowing isolation of the core, direct analysis of its structure, and also the creation of functional nanometer-sized microgels. The key is to employ a macroinitiator (PEG-acetal-Cl) that carries an acetal linkage between a poly(ethylene glycol) arm chain and a chloride initiating site. From this, star polymers were synthesized via the linking reaction with a divinyl monomer and a ruthenium catalyst in living radical polymerization. The arms were subsequently cleaved by acidolysis of the acetal linker to give soluble microgels (cores free from arms). Full characterization revealed that the microgel cores are spherical, nano-sized (<20 nm), and of relatively low density. Amphiphilic, water-soluble, and thermosensitive arm-free microgels can be obtained by additionally employing functional methacrylate upon arm linking.

Protein storage with perfluorinated PEG compartments in a hydrofluorocarbon solvent

We report a novel storage technology of proteins with surface-perfluorinated poly(ethylene glycol) compartments in 2H,3H-perfluoropentane. The compartments were obtained from self-folding and self-assembly of an amphiphilic random copolymer bearing poly(ethylene glycol) and perfluoroalkyl pendants in the hydrofluorocarbon. Lysozyme and α-chymotrypsin as model proteins were efficiently encapsulated within the PEG compartments and quantitatively recovered therefrom with water. The recovered lysozyme maintained the original higher order structure without denaturation to show enzymatic activity for the hydrolysis of Micrococcus lysodeikticus as high as its original counterpart in water. The storage technology was further effective to inhibit inactivation of α-chymotrypsin.

Fluorinated microgel star polymers as fluorous nanocapsules for the encapsulation and release of perfluorinated compounds

Fluorinated microgel star polymers were designed and synthesized as fluorous nanocapsules for the encapsulation and release of perfluorinated compounds. Five types of these fluorous star polymers were obtained by ruthenium-catalyzed linking reaction of chlorine-capped poly(methyl methacrylate) arms (macroinitiators) with a perfluorinated dimethacrylate linker and a perfluorinated methacrylate (RFMA), so as to tune the in-core fluorous properties depending on the latters structure and fluorine content. 19F nuclear magnetic resonance and 19F spin–spin relaxation time (T2) measurements revealed that the mobility of the in-core perfluorinated pendants derived from RFMA decreased on increasing the number of fluorine and carbon atoms, or the pendant length. The cores effectively recognized and encapsulated perfluorinated guest compounds (e.g., perfluorooctane and perfluoromethylcyclohexane), and the encapsulation depended on the fluorous properties of the structures and fluorous nature of RFMA and the guests. For example, encapsulation was promoted by increasing the number of in-core fluorine and CF3 groups, and typically the core with perfluorodecyl pendants successfully captured perfluorinated esters and ketones. In addition, fluorinated star polymers could reversibly capture and thermo-responsively release a perfluorinated guest, indicating that the encapsulation is selective but dynamic and stimuli-responsive.

Design and synthesis of PEGylated amphiphilic block oligomers as membrane anchors for stable binding to lipid bilayer membranes

AbstractCell surface engineering is a potentially powerful method for manipulating living cells by decorating the cell membrane with specific molecules. Possible applications include cell therapy, drug delivery systems, bio-imaging, and tissue engineering. The stable binding of synthetic molecules to serve as artificial membrane protein anchors is a promising approach for appending functional molecules to the cell surface. However, such synthetic molecules have previously shown limitations, including cytotoxicity and low cell surface affinity. We synthesized amphiphilic block oligomers, using ruthenium-catalyzed living radical polymerization, as novel membrane anchors for stable binding to lipid bilayer membranes. AB and ABA-type amphiphilic block oligomers were synthesized with poly(ethylene glycol) methacrylate (PEGMA) and varying butyl methacrylate (BMA) contents (PEGMA/BMA ratios of 25/5–25/50). These PEGylated oligomers showed high binding efficiencies (up to 92%) for liposomes, which served as model cell membranes, and low cytotoxicity in K562 cells. Both the BMA content and the block segment sequence in the copolymers strongly affected their binding efficiencies. Oligomers with an ABA-type block structure were much more effective than AB-type block oligomers, random oligomers, or PEGMA homo-oligomers for stable membrane binding. Thus, precise control of the primary structures of the amphiphilic oligomers enabled tuning of their binding efficiencies. These amphiphilic block oligomers hold promise as novel membrane anchors in many biomedical applications.A series of amphiphilic block oligomers were designed and synthesized using ruthenium-catalyzed living radical polymerization with poly(ethylene glycol) and butyl methacrylates (BMA). These PEGylated oligomers showed high binding efficiencies for liposomal preparations as model cell membranes, and also had low cytotoxicity. BMA contents and monomer sequences in the copolymers strongly affected their binding efficiencies. Current method enabled precise control of the primary structures of amphiphilic oligomers, allowing tuning of their binding efficiencies. These amphiphilic block oligomers have promise as novel membrane anchors for many biomedical applications.