Junyan Zhu

A modulatory bifunctional artificial enzyme with both SOD and GPx activities based on a smart star-shaped pseudo-block copolymer

An artificial smart bifunctional enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was successfully constructed by the self-assembly of a porphyrin core with four suspensory adamantyl moieties and β-cyclodextrin-terminated temperature-sensitive copolymer through host–guest interaction in aqueous solution. The Mn(III) porphyrin, Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M-Ad), was designed as both a “supramolecular linker” and an efficient active site of SOD and the temperature-responsive block copolymer (β-CD-PEG-b-PNIPAAm-Te) with incorporated tellurium moieties in the PNIPAAm chain as GPx active sites was synthesized by ATRP. As a new type of artificial bifunctional enzymes, it exhibited stable SOD-like activity of 0.137 μM (IC50) at 37 °C, and high GPx catalytic efficiency with temperature-responsive dependence characteristic, and the new artificial enzyme was found to exhibit the highest GPx catalytic efficiency (v0 = 8.11 μM min−1) in close to physical temperature.

Dual stimuli-responsive supramolecular pseudo-polyrotaxane hydrogels

THPP-(PEG2000-BA)4, a four-branched molecule end-decorated with benzaldehyde (BA), was successfully designed and synthesized. It can form physical pseudo-polyrotaxane (PPR) hydrogels in the presence of α-cyclodextrins (α-CDs). The branched structure of the THPP core promotes gel formation with a small amount of host and guest. Moreover, these resulting hydrogels are dual stimuli-responsive, which can be observed by physically macroscopical phenomena and 1H NMR spectra. Since BA can react with amine to form a pH-responsive Schiff-base which possesses a dynamic covalent nature, it is anticipated that the formation of gels can be modulated by pH. When THPP-(PEG2000-BA)4 was blocked by the relatively large molecule 6-N-ethylenediamine-6-deoxy functionalized β-CD (EDA-β-CD) gelation did not take place. However, the addition of an acid resulted in gelation since the benzoic imine bonds can hydrolyze under acidic conditions and α-CDs can thus pass through BA to thread on the polyethylene glycol (PEG) chains. When a strongly competitive guest, 1-[p-(phenylazo)benzyl]-bromide (Azo-C1-N+), was added to the gel, a gel-to-sol transition was observed due to the disassembly of inclusion complexes between α-CDs and PEG chains. Simultaneously, this gel shows a photo-responsive capacity because of the presence of azobenzene. Therefore, the cycles of gel–sol transitions were achieved through pH- and photo-stimuli. This kind of hydrogel is promising for use in many fields, such as biology and electronics.

A supramolecular bifunctional artificial enzyme with superoxide dismutase and glutathione peroxidase activities

For constructing a bifunctional antioxidative enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, a supramolecular artificial enzyme was successfully constructed by the self-assembly of the Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M-Ad) and cyclodextrin-based telluronic acid (2-CD-TeO(3)H) through host-guest interaction in aqueous solution. The self-assembly of the adamantyl moieties of Mn(III) porphyrin and the beta-CD cavities of 2-CD-TeO(3)H was demonstrated by the NMR spectra. In this supramolecular enzyme model, the Mn(III) porphyrin center acted as an efficient active site of SOD and tellurol moiety endowed GPx activity. The SOD-like activity (IC(50)) of the new catalyst was found to be 0.116 microM and equals to 2.56% of the activity of the native SOD. Besides this, supramolecular enzyme model also showed a high GPx activity, and a remarkable rate enhancement of 27-fold compared to the well-known GPx mimic ebselen was observed. More importantly, the supramolecular artificial enzyme showed good thermal stability.

Construction of a Hyperbranched Supramolecular Polymer as a Bifunctional Antioxidative Enzyme Model

A HBSP has been designed as a novel bifunctional enzyme model with SOD and GPx activity by host/guest-directed self-assembly of MnTPyP-M-Ad and 6-Te-diCD. The structure of the host/guest complex was elucidated by (1) H NMR spectra, and the HBSP was characterized by SEM, DLS and measurement of catalytic properties. In the bifunctional enzyme model, the Mn(III) porphyrins act as efficient SOD active sites and the tellurol moieties endow GPx activity. The SOD-like activity (IC(50) ) of this new supramolecular catalyst was found to be 1.05 × 10(-7) M, which corresponds to 2.82% of the activity of the native SOD enzyme. Besides this, the hyperbranched supramolecular polymer also shows a higher GPx activity (ν(0 ) = 21.7 × 10(-6) M · min(-1) ) than other supramolecular enzyme models.

Temperature-driven switching of the catalytic activity of artificial glutathione peroxidase by the shape transition between the nanotubes and vesicle-like structures.

Smart supramolecular nanoenzymes with temperature-driven switching property have been successfully constructed by the self-assembly of supra-amphiphiles formed by the cyclodextrin-based host-guest chemistry. The self-assembled nanostructures were catalyst-functionalized and thermosensitively-functionalized through conveniently linking the catalytic center of glutathione peroxidase and thermosensitive polymer to the host cyclodextrin molecules.The ON-OFF switches for the peroxidase activity by reversible transformation of nanostructures from tube to sphere have been achieved through changing the temperature. We anticipate that such intelligent enzyme mimics could be developed to use in an antioxidant medicine with controlled catalytic efficiency according to the needs of the human body in the future.

Design of aromatic helical polymers for STM visualization: imaging of single and double helices with a pattern of π-π stacking.

From scanning tunneling microscopy (STM) images of rationally designed helical polymers with a pattern of π-π stacking, we successfully identified the single- and double-helical superstructures. The STM images of the helical structures revealed the smallest helical architecture (diameter ca. 1.3 nm) that has been seen so far. Furthermore, the interconversion of single and double helices was further underpinned by experimental analyses. Significantly, the formation of double helices induced different supramolecular chirality to that observed for the single helices.

Understanding enzyme catalysis by means of supramolecular artificial enzymes

Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved during the processes catalyzed by enzymes. It is plausible that the entire macromolecular scaffold is involved in catalysis via cooperative motions that result in incredible catalytic efficiency. Moreover, some enzymes can very strongly bind the transition state with an association constant of up to 1024 M−1, suggesting that covalent bond formation is a possible process during the conversion of the transition state in enzyme catalysis, in addition to the concatenation of non-covalent interactions. Supramolecular chemistry provides fundamental knowledge about the relationships between the dynamic structures and functions of organized molecules. By taking advantage of supramolecular concepts, numerous supramolecular enzyme mimics with complex and hierarchical structures have been designed and investigated. Through the study of supramolecular enzyme models, a great deal of information to aid our understanding of the mechanism of catalysis by natural enzymes has been acquired. With the development of supramolecular artificial enzymes, it is possible to replicate the features of natural enzymes with regards to their constitutional complexity and cooperative motions, and eventually decipher the conformation-based catalytic mystery of natural enzymes.