Jiatao Yan

Stimuli-Responsive Zwitterionic Block Copolypeptides: Poly(N-isopropylacrylamide)-block-poly(lysine-co-glutamic acid)

Synthesis of novel zwitterionic block copolypeptides, poly(N-isopropylacrylamide)-block-poly(L-glutamic acid-co-L-lysine) [PNiPAM(n)(PLG(x)-co-PLLys(y))m , where n is the number-average degree of polymerization (DP(n)) of PNiPAM block, x and y are the mole fraction of glutamic acid and lysine residues, respectively, and m is the total DP(n) of the peptide block], and their stimuli-responsiveness to temperature and pH variation in aqueous solutions are described. Initiated with the amino-terminated poly(N-isopropylacrylamide) (PNiPAM(n)-NH2), ring-opening polymerization (ROP) of a mixture of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA), and Boc-L-lysine N-carboxyanhydride (BLLys-NCA) afforded the block copolypeptides PNiPAM(n)(PBLG(x)-co-PBLLys(y))m, with a poly(N-isopropylacrylamide) block together with a random copolypeptide block, which was then deprotected with HBr/trifluoroacetic acid into the double hydrophilic block copolypeptides, PNiPAM(n)(PLG(x)-co-PLLys(y))m. Their block ratios and lengths, as well as the amino acid residue ratios in the random copolypeptide block are varied (n = 360, x = 0.4-0.5, y = 0.4-0.6, and m = 220-252). The secondary structures of the copolypeptides in aqueous solution at different pH conditions were examined. Phase transitions in aqueous solutions induced by both pH and temperature variation were investigated by (1)H NMR spectroscopy. The transitions induced by temperature were also explored by turbidity measurements using UV/vis spectroscopy for their lower critical aggregation temperature (LCAT) determination. Furthermore, these aggregation processes were followed by dynamic light scattering measurements.

Thermoresponsive Supramolecular Dendronized Polymers

Combining the concepts of supramolecular polymers and dendronized polymers provides the opportunity to create bulky polymers with easy structural modification and tunable properties. In the present work, a novel class of side-chain supramolecular dendronized polymethacrylates is prepared through the host-guest interaction. The host is a linear polymethacrylate (as the backbone) attached in each repeat unit with a β-cyclodextrin (β-CD) moiety, and the guest is constituted with three-fold branched oligoethylene glycol (OEG)-based first-(G1) and second-generation (G2) dendrons with an adamantyl group core. The host and guest interaction in aqueous solution leads to the formation of the supramolecular polymers, which is supported with (1)H NMR spectroscopy and dynamic light scattering measurements. The supramolecular formation was also examined at different host/guest ratios. The water solubility of hosts and guests increases upon supramolecular formation. The supramolecular polymers show good solubility in water at room temperature, but exhibit thermoresponsive behavior at elevated temperatures. Their thermoresponsiveness is thus investigated with UV/Vis and (1)H NMR spectroscopy, and compared with their counterparts formed from individual β-CD and the OEG dendritic guest. The effect of polymer concentration and molar ratio of host/guest was examined. It is found that the polar interior of the supramolecules contribute significantly to the thermally-induced phase transitions for the G1 polymer, but this effect is negligible for the G2 polymer. Based on the temperature-varied proton NMR spectra, it is found that the host-guest complex starts to decompose during the aggregation process upon heating to its dehydration temperature, and this decomposition is enhanced with an increase of solution temperature.

Thermoresponsive supramolecular dendronized copolymers with tunable phase transition temperatures

Supramolecular copolymerization from a mixture of comonomers with different hydrophilicities may offer an easy and convenient access to form thermoresponsive supramolecular copolymers with varied phase transition temperatures by simply varying ratios of the comonomers. Herein, supramolecular dendronized copolymers (SDCPs) were constructed via host–guest interaction from a linear polymer carrying β-cyclodextrin units (the host) and a mixture of two adamantyl-cored second generation oligo(ethylene glycol) dendrons (the guests). The phase transition temperatures of these SDCPs can be tuned continuously in the range of 34–56 °C by varying the ratios of the dendritic guests. To check the possible effects of steric hindrance and hydrophilicity of the guests on the supramolecular complexation, isothermal titration calorimetry was applied to follow the complexation process of the first (G1) and second generation (G2) dendritic guests. Proton NMR spectroscopy was utilized to follow dehydration and collapse processes of SDCPs. It was found that the dehydration and collapse of the OEG units initiated decomposition of the dendritic guests from the supramolecular copolymers, and the more hydrophobic guest dissociated at a much lower temperature than that for the more hydrophilic one.

OEGylated cyclodextrin-based thermoresponsive polymers and their switchable inclusion complexation with fluorescent dyes

Using oligo(ethylene glycol)s (OEG)-modified β-cyclodextrin (CyD) as the building block, a new class of thermoresponsive polymers carrying CyD pendants with switchable inclusion ability are reported. Their synthesis, thermoresponsive behaviour and host–guest chemistry are described. Similar to other OEG-based polymers, these CyD polymers exhibit characteristic thermoresponsive properties. Their thermoresponsiveness and complexation behaviour are compared with their corresponding monomers to demonstrate the macromolecular effect. Notably, OEG moieties are found to cooperatively participate in the inclusion complexation with fluorescent dyes (guests). This cooperative interaction results in strong induced circular dichroism and significantly fluorescence enhancement from the guest dyes. These encapsulated guest dyes can be easily released at elevated temperature, associated with obvious fluorescence quenching, which makes these CyD polymers ideal candidates as scaffolds for thermoresponsive fluorescent sensors.

Lysine-based dendronized polymers with preferred chirality

Dendronized polymethacrylates carrying lysine-based third generation (G3) dendrons were efficiently synthesized via a macromonomer route by free radical polymerization. These polymers showed amplified chirality when compared to the corresponding free dendrons, and the handedness of their chiral conformations could be mediated by the diastereomeric dendrons.

Thermoresponsive cyclodextrins with switchable inclusion abilities

Cyclodextrins (CDs) modified with oligoethylene glycols (OEGs) show unprecedented thermoresponsive properties in aqueous solutions and their phase transition temperatures can be mediated in the range of 24–63 °C depending on the ring size of CDs and the structure of the OEG units. Their synthesis, thermoresponsive behavior, and host-guest chemistry are described herein. Similar to the native CDs, these CD derivatives display strong inclusion ability for dyes below the phase transition temperatures. Moreover, the encapsulated dyes can be easily released due to the dehydration of OEG units at elevated temperatures, associated with an obvious color change of the aqueous solutions, which makes these CD species unique as scaffolds for colorimetric sensors.

Metal-ion mediated supramolecular assembly of C3-peptides

An investigation on a supramolecular assembly of C3 -molecules benzene-1,3,5-tricarboxamides carrying tetrapeptide Gly-Ala-Gly-Ala pendants promoted by hydrogen bonding and metal ion coordination is described. A Gly-Ala peptide sequence was selected as it is the most abundant repeating unit in silkworm silk, and known to form β-sheets through efficient intermolecular hydrogen bonds. These C3 -peptides formed long helical fibers in solvents mainly owing to strong hydrogen bonding. However, in the presence of divalent metal ions, chirality of these helical fibers was enhanced through metal coordination and could be transformed into nanospheres with an excess amount of the ions. Different metal ions show different tendencies to mediate the supramolecular chirality, which can even be inverted according to coordination differences.

Thermoresponsive dynamic covalent dendronized polymers

Thermoresponsive dendronized polymers constituted with a polyacylhydrazone backbone pendanted with oligoethylene glycol (OEG)-based dendrons were synthesized through polycondensation of dialdehydes and diacylhydrazines. First (G1) and second (G2) generation OEG dendrons were selected for comparison to examine the dendritic effects. Inherited from OEG dendrons, these polymers showed characteristic thermoresponsive behavior. By virtue of the dynamic property of the acylhydrazone linkage, formation of these polymers are concentration and pH-dependent. A dimer from monoaldehyde and monoacylhydrazine was prepared as a model to support the remarkable macromolecular effects for enhanced structural stability of polyacylhydrazones. Constitutional stability of these polyacylhydrazones were also testified by switching solutions to strong acidic or basic conditions. The structural vibration was simply testified by addition of a new monomer as a competitor to dendronized polyacylhydrazones, thus, resulting in polymers with tunable phase transition temperatures. Furthermore, G1 dendrons were found to provide efficient shielding for acylhydrazones from an affinity to metal ions, but this shielding effect diminished and exhibited specific interactions with Cu2+ when the dendron collapsed.

Thermo- and redox-responsive dendronized polymer hydrogels

In order to combine dendritic structures and thermoresponsiveness within the field of metallo-supramolecular chemistry, a novel type of smart hydrogel was prepared through ferrous ion-induced supramolecular interactions from oligoethylene glycol (OEG)-based, first-generation (G1) dendritic copolymers containing terpyridine (Tpy) moieties. These hydrogels show both thermally-induced reversible shrunk-swelling and redox-mediated gel–sol transitions. Rheological analyses by rotational rheometry revealed that their storage modulus (G′) and loss modulus (G′′) were dependent on crosslinking density through changing the molar ratio of metal ions and Tpy moieties, as well as the copolymer composition with different ratios of OEG dendron and Tpy units. Copolymers pendanted with linear OEG units and second-generation (G2) dendrons were also prepared to compare the possible effects of architecture on the formation of hydrogels and their properties. By virtue of the thermoresponsiveness of these dendronized copolymers, hydrogels were further prepared through crosslinking of aggregates above the polymer phase-transition temperatures, which provides a convenient strategy to afford hydrogels with much improved elastic modulus. Moreover, encapsulation and thermally-mediated transition of the model drug from the hydrogels were investigated, to demonstrate the unique confinement from the OEG-based dendronized polymer matrix. This report provides not only a first route to fabricate intelligent hydrogels from dendronized copolymers through metal ions-mediated coordination, but also proves that thermoresponsive hydrogels with enhanced mechanical properties could be simply prepared by crosslinking thermally-induced polymer aggregates.