Junlian Huang

A novel kind of antitumour drugs using sulfonamide as parent compound.

To obtain potent antitumour agents with low toxicity, sulfonamide derivatives containing 5-flurouracil and nitrogen mustard, respectively are designed and synthesised. 1-(3-(4-Acetylaminobenzenesulfonamido)-3-oxopropyl)-5-fluoropyrimidine-2,4-dione (4) was obtained by the coupling of p-acetamidobenzenesulfonamide with 3-(5-fluorouracil-1-yl) propionic acid. The hydrolysis of 4 led to 1-(3-(4-aminobenzenesulfonamido)-3-oxopropyl)-5-fluoropyrimidine-2,4-dione (5). Treatment of p-acetamidobenzenesulfonyl chloride with bis(2-chloroethyl) amine led to 4-acetylamino-N,N-bis(2-chloroethyl)benzenesulfonamide (6). Subsequent hydrolysis of 6 in hydrochloric acid led to 4-amino-N,N-bis(2-chloroethyl)benzenesulfonamide hydrochloride (7). Two different synthetic route were investigated in the synthesis of 2-[N(1)-2-pyrimidyl-aminobenzenesulfonamido] ethyl 4-bis(2-chloroethyl) aminophenyl butyrate (12b). Carbobenzyloxy was proved to be unsuitable for the protection of the aromatic amino group of sulfadiazine since the pyrimidine ring was also hydrogenated at the last step of the first route under the deprotection condition. In another route, acetyl was firstly used as the protective group, then it was replaced by the Schiffs base. The reaction of chlorambucil with 2-[N(1)-2-pyrimidinyl-(p-acetyl)aminobenzenesulfonamido] ethanol (10b) afforded 2-[N(1)-2-pyrimidinyl-(p-benzylidene)aminobenzenesulfonamido] ethyl 4-bis(2-chloroethyl) aminophenyl butyrate (11b). Compound 12b was obtained by the hydrolysis of 11b. The acute toxicity and antitumour activity of 5, 7 and 12b have been investigated in mice. Compound 12b exhibited high antitumour activity and low toxicity with a therapeutic index (TI) of 47.55.

Synthesis of PPEGMEA-g-PMAA densely grafted double hydrophilic copolymer and its use as a template for the preparation of size-controlled superparamagnetic Fe3O4/polymer nano-composites

A series of well-defined amphiphilic densely grafted copolymers, containing polyacrylate backbone, hydrophobic poly(methoxymethyl methacrylate) and hydrophilic poly(ethylene glycol) side chains, were synthesized by successive atom transfer radical polymerization. Poly[poly(ethylene glycol) methyl ether acrylate] comb copolymer was firstly prepared via the grafting-through strategy. Next, poly[poly(ethylene glycol) methyl ether acrylate]-g-poly(methoxymethyl methacrylate) amphiphilic graft copolymers were synthesized via the grafting-from route. Poly(methoxymethyl methacrylate) side chains were connected to the polyacrylate backbone through stable C–C bonds instead of ester connections. The molecular weights of both the backbone and the side chains were controllable and the molecular weight distributions were in the range 1.38–1.42. Poly(methoxymethyl methacrylate) side chains were selectively hydrolyzed under mild conditions without affecting the polyacrylate backbone to obtain the final product, poly[poly(ethylene glycol) methyl ether acrylate]-g-poly(methacrylic acid) densely grafted double hydrophilic copolymer. Finally, these double hydrophilic copolymers were used as templates to prepare superparamagnetic Fe3O4/polymer nano-composites with narrow size distributions via an in situco-precipitation process, which were characterized by FT-IR, TGA, DLS and X-ray diffraction in detail. The size of the nano-composites can be controlled in a certain range by adjusting the length of the poly(methacrylic acid) side chains and the weight ratio of copolymer to Fe3O4 nano-particle used.

Versatility of radical coupling in construction of topological polymers

The development of various polymerization mechanisms has paved the way for the construction of well-defined polymers with complicated structures. However, a single polymerization mechanism or a simple combination of several mechanisms often cannot meet the requirements. Thus, some efficient coupling reactions would play an important role in polymer science. In this review, we focused on the application of radical coupling in the construction of topological polymers. The atom transfer radical coupling (ATRC) reaction and agent (such as styrene, nitrone or diene) assisted radical coupling proceeded in a homocoupling style and polymers with symmetrical structures were obtained. As a more versatile method, nitroxide radical coupling (NRC) was also discussed, which proceeded in a heterocoupling style and polymers with various asymmetrical structures could be designed. Finally, the prospects of radical based coupling reactions in polymer science were also suggested.

Synthesis and Characterization of Amphiphilic Diblock Copolymer of Polystyrene and Polyvinyl Alcohol Using Ethanolamine-Benzophenone as Photochemical Binary Initiation System

Amphiphilic diblock copolymers of polyvinyl alcohol (PVA) and polystyrene (PS), which are very difficult to prepare by common polymerization methods, have been obtained by initiation of the polymerization of styrene and vinyl acetate successively, followed by hydrolysis, using the ethanolamine-benzophenone (BP) charge-transfer complex (CTC). The effects of solvents, concentration of monomer, BP, ethanolamine, and PS prepolymer, with a reactive imino group (PSa), on the photo-induced charge- transfer polymerization (CTP) of St and block copolymerization of VAc are discussed. The copolymer of PS-b-PVAc and the hydrolyzed product, PS-b-PVA, were characterized by FTIR, NMR, and GPC in detail. The effect of PS chain length on the crystallization of PVA was described. q 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 109- 115, 1998

Synthesis and characterization of linear ABC triblock copolymer of ethylene oxide, methyl methacrylate, and styrene

A well-defined linear ABC triblock copolymer of ethylene oxide (EO), methyl methacrylate (MMA), and styrene (St) was prepared by sequential living an- ionic and photo-induced charge transfer polymerization (CTP) using p-aminophenol as parent compound. In the first step, the diblock copolymer of PEO-b-PMMA with a protected aniline end group at PEO end was prepared by initiating of phenoxo-anion the polymerization of EO and MMA successively, then the diblock copolymer of PEO- b-PMMA via deprotection of aniline at PEO end constituted a binary initiation system with benzophenone (BP) by charge transfer complex mechanism to initiate the poly- merization of St under UV-irradiation. The GPC and NMR measurements support that in copolymerization, either in the first or second step, neither homopolymer nor side reactions, such as chain transfer or chain termination, was found. The effect of the concentration of PEOa-b-PMMA and St, and the polarity of solvent on the polymeriza- tion rate (Rp) of CTP is discussed.

Copolymerization of ethyl α-(hydroxymethyl)acrylate with maleimide and characterization of the resulting copolymer

Copolymerization of maleimide (MI) and ethyl α-(hydroxymethyl)acrylate (EHMA) was performed at 60°C with AIBN as the initiator in THF. The monomer reactivity ratios were determined as r1 (MI) = 0.13 and r2 (EHMA) = 2.20. As the molar fraction of MI in the monomer feed increased, the initial rate of copolymerization decreased. TGA diagrams suggested the crosslinking reaction of the copolymer on heating. DSC and WAXD results suggested the existence of incomplete crystallinity in the copolymer.

Alternating Copolymerization of Maleimide and Ethyl Atropate Without Initiator

ABSTRACT The copolymerization of maleimide(MI)(M1) and ethyl atropate (EAP)(M2) was carried out by self-initiation at 60°C, in which M2(Q=0.43, e=0.92) and M1 (Q=0.44, e=1.35) constituted a pair of electron donor and acceptor monomers on Price-Alfrey equation. A high alternating tendency was observed, the monomer reactivity ratios r1 =0.048±0.016 and r2=0.12±0.012 were calculated by a nonlinear least-squares procedure. The spontaneous alternative copolymerization is considered to be carried out by the induced radicals produced via a contact-type charge transfer complex between M1 and M2, which was confirmed by UV spectra. Thermogravimetric analysis (TGA) shows that the resulting copolymers have high thermal stability.

Preparation of PEO with amine and sulfadiazine end groups by anion ring‐opening polymerization of ethylene oxide

Polyethylene oxides with amine and sulfadiazine end groups (PEOa-sf) were prepared by alkoxy-anion ring-opening polymerization of ethylene oxide (EO); the potassium aminoethoxide with a protected amino group was used as initiator. The living polyethylene oxide anions was terminated by methanol first, then the separated polymer was continuously reacted to bromacetic acid in the presence of metal sodium. After that the purified intermediate was reacted sequentially with benzoyl chloride and sulfadiazine, then hydrolyzed with acetic acid. The final product PEOa-sf and all intermediates are characterized in detail by IR, NMR, GPC, and chemical analysis; the effect of reaction conditions on the preparation of polyethylene oxides with various functional end groups are discussed.

Synthesis and Characterization of a Diblock Copolymer of Methyl Methacrylate and Vinyl Acetate by Successive Photo-Induced Charge Transfer Polymerization Using Ethanolamine as the Parent Compound

A diblock copolymer consisting of poly(methyl methacrylate) (PMMA) and poly(vinyl acetate) (PVAc) with hydroxyl group at one end is prepared by successive charge transfer polymerization (CTP) under UV irradiation at room temperature using ethanolamine and benzophenone as a binary initiation system. The diblock copolymer PMMA-b-PVAc could be selectively hydrolyzed to the block copolymer of poly(methyl methacrylate) and poly(vinyl alcohol) (PVA) using sodium ethoxide as the catalyst. Both copolymers, PMMA-b-PVAc and PMMA-b-PVA, are characterized in detail by means of FTIR and 1 H NMR spectroscopy, and GPC. The effect of the solvent on CTP and the kinetics of CTP are discussed.

Synthesis of Poly(Ethylene Glycol) with Sulfadiazine and Chlorambucil End Groups and Investigation of Its Antitumor Activity

alpha-Amino-omega-hydroxyl-poly(ethylene glycol) (PEG) with different molecular weight (M(r)=2100, 4400, 7200) were synthesized and used as carrier for the combination of sulfadiazine and chlorambucil. In vivo, all these polymer drugs with sulfadiazine and chlorambucil at each end are water soluble and showed the higher antitumor activity against Lewis lung cancer than the same polymers but without the sulfadiazine. The best one is the sample with molecular weight of 2100. In vitro, however, for the samples with same molecular weights, the polymer drugs with and without sulfadiazine showed the similar results against C6 human breast cancer cells. No obvious difference was found.