Fu-Sheng Du

One-pot synthesis of polyamides with various functional side groups via Passerini reaction

Polyamides with various functional side groups were synthesized via Passerini reaction in a one-pot approach. The polymerization conditions and kinetics as well as the resulting polymer structures were thoroughly investigated. The facile introduction of various pendant groups, especially alkynyl and alkenyl groups, provides a platform for efficient post-polymerization modification by click chemistry.

Targeted minicircle DNA delivery using folate-poly(ethylene glycol)-polyethylenimine as non-viral carrier

Targeted gene delivery systems have attracted great attention due to their potential in directing the therapeutic genes to the target cells. However, due to their low efficiency, most of the successful applications of polymeric vectors have been focused on genes which can achieve robust expression. Minicircle DNA (mcDNA) is a powerful candidate in terms of improving gene expression and prolonging the lifespan of gene expression. In this study, we have combined folate/poly(ethylene glycol) modified polyethylenimine and mcDNA as a new tumor gene delivery system. We found that folate-labeled polyplexes were homogenous, with a size ranging from 60 to 85 nm. mcDNA increased folate-labeled vector based gene expression 2-8 fold in folate receptor-positive cells. Results of folic acid competition assay indicated that mcDNA mediated by folate-labeled vector were internalized into cells through receptor-mediated endocytosis. The investigation of the endocytosis pathway of the polyplexes showed that a large portion of them escaped from endo/lysosome and the polyplexes were associated before being separated in the nucleus. Furthermore, in vivo optical imaging and luciferase assays demonstrated that systemic delivery of the folate-labeled polyplexes resulted in preferential accumulation of transgenes in folate receptor-positive tumors, and mcDNA mediated approach achieved 2.3 fold higher gene expressions in tumors than conventional plasmid. Cytotoxicity assays showed that PEG-shielding of the polyplexes reduced the toxicity of PEI.

Oxidation-responsive polymers for biomedical applications

Reactive oxygen species (ROS) play key roles in many physiological processes, such as cell signaling and host innate immunity. However, when they are overproduced, ROS may damage biomolecules in vivo and cause diseases such as cardiovascular or neurodegenerative diseases, cancer, and so forth. Oxidative stress is usually implicated in various inflammatory tissues, representing an important target for the development of various therapeutic strategies. Therefore, various probes for the in vitro detection of ROS or the in vivo diagnosis of the oxidative stress-relevant diseases have been developed. Oxidation-responsive polymers have also attracted great interest due to their potential applications in biomedical fields. In this feature article, we summarize six types of oxidation-responsive polymers based on different oxidation-responsive motifs. Poly(propylene sulfide)s, selenium-based polymers, aryl oxalate- and phenylboronic ester-containing polymers are discussed in detail, while poly(thioketal)s and proline-containing polymeric scaffolds are briefly introduced.

Facile synthesis of multi-block copolymers containing poly(ester–amide) segments with an ordered side group sequence

We report a facile method for the synthesis of multi-block copolymers consisting of poly(ethylene glycol) (PEG) and poly(ester–amide) segments with an ordered side group sequence via multicomponent polymerization based on the Passerini reaction (PR). The technique involves the polymer supported liquid-phase synthesis of three PEG diacid macromonomers (M1–M3) via stepwise PR with tert-butyl isocyanoacetate and a functional aldehyde followed by selective hydrolysis, and the final multicomponent polymerization of M1–M3 with phenylacetaldehyde and 1,6-diisocyanohexane.

Functional highly branched polymers from multicomponent polymerization (MCP) based on the ABC type Passerini reaction

A new synthetic approach to prepare functional highly branched polymers (HBPs) is demonstrated via the multicomponent polymerization (MCP) of easily accessible hexanedioic acid (A2), hexane-1,6-dial (B2), 1,6-diisocyanohexane (C2) and 10-undecenoic acid (A). Both the degree of branching (DB) and the degree of additional functionalization (DF) were regulated by simply varying the ratio of A2 to A.

Bismaleimides Having Electron-Donating Chromophore Moieties: A New Approach Toward Monitoring the Process of Curing Based on Their Fluorescence Behavior

Bismaleimides having electron-donating diphenylmethylamine or triphenylamine moieties (A (=) -D (*) -A (=) , as well as their saturated model compounds were synthesized. Their fluorescence behavior was found to show a strong fluorescence structural self-quenching effect (SSQE). On the basis of this strong SSQE of A (=) -D (*) -A (=) bismaleimides, a new fluorescence approach can be developed to monitor the curing process in bismaleimide resins, which is in agreement with the results from FT-IR and 1 H NMR analyses.

Vinyl monomers bearing chromophore moieties and their polymers. V. Synthesis and fluorescence behavior of a vinyloxy monomer bearing electron-accepting chromophore moiety, N-(2-(vinyloxy)ethyl)-1,8-naphthalimide, and its polymer

A vinyloxy monomer bearing electron-accepting chromophore, N-(2-(vinyl-oxylethyl)-1,8-naphthalimide (VOENI), was synthesized by reaction of potassium 1,8-naphthalimide with 2-chloroethyl vinyl ether. VOENI can be homopolymerized by cationic initiation and copolymerized with maleic anhydride (MAn) under radical initiation. The fluorescence behaviors of VOENI and its polymers were investigated. It has been found that the fluorescence intensity of the VOENI monomer is much lower than that of its polymers at the same chromophore concentration. This means that a structural self-quenching effect (SSQE) has been also observed in the vinyloxy monomer consisting of an electron-accepting chromophore, which has opposite electronic structure in comparison with acrylates bearing electron-donating chromophores as we have reported previously. The SSQE is attributed to the charge-transfer interaction between the electron-accepting chromophore and the electron-donating double bond in the same molecule. The fluorescence quenching of 1,8-naphthalic anhydride and P(VOENI-co-MAn) by ethyl vinyl ether (EVE), dihydrofuran, triethylamine (TEA), etc. evidences that the electron-rich vinyloxy group does act as an important role in the SSQE of VOENI. C 60 can also quench the fluorescence of the polymers, and an upward deviation from the linearity of the Stern-Volmer plot was observed showing that C 60 acted as a powerful electron donor to quench the fluorescence of the copolymer.

A unique synthesis of a well-defined block copolymer having alternating segments constituted by maleic anhydride and styrene and the self-assembly aggregating behavior thereof

A unique synthesis of a well-defined block copolymer having alternating maleic anhydride(MAn)/styrene(St) segments and PSt segments was achieved via radical addition–fragmentation chain transfer (RAFT) copolymerization and the self-assembly aggregating behavior of its hydrolyzed amphiphilic product in water was demonstrated.

Acyclic diene metathesis polymerization of tailor-made monomers towards sequence-regulated vinyl copolymers

Acyclic diene metathesis polymerization (ADMET) enables convenient transfer of sequential information of the designed monomers to the corresponding sequence-regulated copolymers. In this study, two structurally symmetric monomers, M1 and M2, were synthesized via atom transfer radical addition (ATRA) of diethyl meso-2,5-dibromohexanedioate with 1,5-hexadiene and 1,7-octadiene, respectively. Thus, sequenced segment of VB-EA-EA-VB (VB and EA represent vinyl bromide and ethyl acrylate, respectively) was incorporated into the ADMET diene monomers. ADMET polymerization of these two monomers with Grubbs first generation catalyst (Grubbs-I) was performed in CH2Cl2 at 40°C for 5 days under nitrogen purge. Effects of catalyst amount, monomer concentration and methanol precipitation on the Mp and PDI of polymers were investigated by GPC, and the structures of the formed polymers were characterized by NMR. Our results indicate that using 3.0 mol% of Grubbs-I to monomer can afford polymers with high Mp. Moreover, selective precipitation in methanol enables complete removal of low molecular weight components from the crude products. Meanwhile, M2 exhibits higher ADMET polymerization reactivity than M1 due to its capability of suppressing negative neighboring group effect.

Synthesis of linear functionalized polyesters by controlled atom transfer radical polyaddition reactions

We report on the facile synthesis of a range of new linear functionalized polyesters by controlled atom transfer radical polyaddition reactions. One bis-styrenic type monomer, 1,2-bis(4-vinylbenzyloxy)ethane (AA), and two bis-methacrylate type ATRP initiators, 1,2-bis(2-bromoisobutyryloxy)ethane (BB) and bis[2-(2-bromoisobutyryloxy)ethyl]disulfide (BssB), were synthesized. The polymerizations of monomer AA with BB and BssB were carried out in anisole at 0 °C, using Cu/CuBr2 coupled with N,N-bis(2-pyridylmethyl)octylamine (BPMOA) as the catalyst. The polymerization kinetics were investigated and the polymers were characterized by GPC and NMR, both confirming the step-wise mechanism with the formation of the expected linear polyesters having pendent bromides. When BssB was used, additional disulfide groups were incorporated in the polyester main chain, imparting a tunable degradation mechanism to the polyester. Moreover, the pendent bromides on the polymers could serve as initiation sites or precursors to azides to prepare biodegradable graft copolymers. This has been proven by two examples, reactivating the pendent bromides at room temperature to initiate the ATRP of other methacrylates, and transforming these groups into azido-groups by substitution reaction followed by click chemistry with alkynyl-terminated polyethylene glycol.