Biocatalytic fabrication of fast-degradable, water-soluble polycarbonate functionalized with tertiary amine groups in backbone.
Degradable polymers with specifically designed functionality have wide applications in biomedical fields. We reported herein the synthesis and characterization of a water-soluble and fast-degradable polycarbonate, functionalized with tertiary amine groups in the backbone. A novel cyclic carbonate monomer, namely, 6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione (ADMC)(2), was synthesized and polymerized to provide the title polycarbonate [poly(ADMC)] via Novozym-435 lipase or tin(II) 2-ethylheaxanoate [Sn(Oct)(2)] catalyzed ring-opening polymerization (ROP). Novozym-435 lipase exhibited high activity toward the ROP in terms of molecular weight (M(n)) and monomer conversion, whereas the attempt with Sn(Oct)(2) failed. In the presence of molecular sieves-4 Å, the highest M(n) value of 1.2 × 10(4) g/mol was obtained in toluene with an initial monomer concentration of 0.58 M at 75 °C in the presence of 10 wt % of Novozym-435 to the monomer. Parameters that influence the polymerization, including reaction temperature, enzyme concentration, monomer concentration, and solvent composition, were investigated systematically. The resultant data suggested "living" characteristics for this enzyme-catalyzed polymerization, and the "living" feature seemed independent of the lipase concentration. The polymerization conducted in mixed solvents (toluene/isooctane) showed that product M(n)s were heavily dependent on the solvent composition. Poly(ADMC) was demonstrated to be amorphous by DSC technique. The obtained poly(ADMC) was found to be soluble in most of the organic solvents and interestingly in H(2)O as well. In vitro hydrolytic degradation of poly(ADMC) as monitored by GPC indicated the degradation was a relatively fast process. HPLC-ESI/MS and (1)H NMR analyses demonstrated that N-methyl diethanolamine was the main product after degradation. Poly(ADMC) presented low cytotoxicity toward human cervix carcinoma (HeLa) cells and hepatoblastoma cells (Hep G2), as demonstrated by MTT assay.
Wang
Hua-Fen
HF
Key Laboratory of Biomedical Polymers (The Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, Hubei, China.
Su
Wei
W
Zhang
Chao
C
Luo
Xiao-hua
XH
Feng
Jun
J
D000588:Amines / Q000737:chemistry*; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D006573:Heterocyclic Compounds, 1-Ring / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D008049:Lipase / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011091:Polyesters / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D058105:Polymerization; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D014867:Water / Q000737:chemistry
D000588:Amines; D001672:Biocompatible Materials; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D006573:Heterocyclic Compounds, 1-Ring; D007783:Lactones; D011091:Polyesters; D014867:Water; C093667:Novozyme 435; D008049:Lipase