【作者】 裴立军；

【导师】 宋湛谦；

【作者基本信息】 中国林业科学研究院 ， 林产化学加工工程， 2014， 博士

【摘要】 高分子表面活性剂是一类分子量在几千至几万以上且有表面活性的高分子化合物，因其兼有高分子化合物和表面活性剂的性能，故越来越受到广泛的关注。本论文以脱氢枞胺为原料首次合成了3-氯-2-羟丙基脱氢枞基氯化铵(CHPDMDHA)和烯丙基二甲基脱氢枞基氯化铵(ADMDHA)，并创新提出以CHPDMDHA和ADMDHA作为活性季铵盐对壳低聚糖(LWCTSs)、N-羧甲基壳聚糖(N-CMC)、N,O-羧甲基壳聚糖(N,O-CMC)、N-羧乙基壳聚糖(N-CEC)和N,O-羧乙基壳聚糖(N,O-CEC)进行改性，分别得到了CHPDMDHA接枝壳低聚糖(CHPDMDHA-g-LWCTSs)、CHPDMDHA接枝羧烷基壳聚糖(CHPDMDHA-g-CACTSs)、ADMDHA接枝壳低聚糖(ADMDHA-g-LWCTSs)和ADMDHA接枝羧烷基壳聚糖(ADMDHA-g-CACTSs)等4个系列松香改性壳聚糖类梳型高分子表面活性剂。采用FT-IR、NMR、元素分析等手段表征了产物结构，并研究了所合成化合物的表面活性、乳化性能、抑菌性能及抗肿瘤活性，初步探讨了这些典型性能与结构间的关系，研究结果对松香改性壳聚糖类高分子表面活性剂的开发有一定理论指导意义。采用吊片法研究了CHPDMDHA、ADMDHA和松香改性壳聚糖类梳型高分子表面活性剂的表面活性。结果表明，CHPDMDHA、ADMDHA和松香改性壳聚糖类梳型高分子表面活性剂都具有较好的表面活性。CHPDMDHA的表面活性优于结构相似的C12～C16烷基二甲基苄基氯化铵，ADMDHA的表面活性也优于结构相似的C16或C18的烷基二甲基烯丙基氯化铵。松香改性壳聚糖类梳型高分子表面活性剂的临界胶束浓度(cmc)介于0.75×10-4～7.31×10-2mol/L之间，且随壳低聚糖分子量的增大而增大，随季铵化度(DQ)的增加而减小；cmc时对应的表面张力(γcmc)介于31.4～39.4mN/m之间，且随壳低聚糖分子量的增大或DQ的增加而降低。研究了CHPDMDHA、ADMDHA和松香改性壳聚糖类梳型高分子表面活性剂对基于液体石蜡-水乳液体系稳定性的影响。结果表明，CHPDMDHA的乳化性能优于C12～C16烷基二甲基苄基氯化铵；ADMDHA的乳化性能优于C16或C18的烷基二甲基烯丙基氯化铵。 CHPDMDHA-g-LWCTSs、 CHPDMDHA-g-CACTSs、 ADMDHA-g-LWCTSs、ADMDHA-g-CACTSs的乳液稳定时间均随DQ的增加或壳低聚糖分子量的增大而延长。采用平板二倍稀释法测定了CHPDMDHA、ADMDHA、羧烷基壳聚糖(CA-CTS)、CHPDMDHA-g-LWCTSs、 CHPDMDHA-g-CACTSs、 ADMDHA-g-LWCTSs和ADMDHA-g-CACTSs对绿脓杆菌(Pseudomonas aeruginosa)、产气肠杆菌(Escherichiaaerogenes)、肺炎克雷伯氏菌(Klebsiella pneumonia)和大肠埃希氏杆菌(Escherichia coil)等革兰氏阴性菌及金黄色葡萄球菌(Staphylococcus aureus)和表皮葡萄球菌(Staphylococcusepidermidis)等革兰氏阳性菌的最小抑菌浓度(MIC值)，初步研究了它们的抑菌性能与其结构间的关系。结果表明：CHPDMDHA、ADMDHA对金黄色葡萄球菌和表皮葡萄球菌抑制作用明显，其MIC值分别为16和64及8和8μg/mL；CA-CTS对大肠埃希氏杆菌、表皮葡萄球菌和绿脓杆菌的抑菌效果较好，且CA-CTS的抑菌能力随其取代度或分子量的增加而降低；CHPDMDHA-g-LWCTSs对绿脓杆菌抑制作用尤为明显，其MIC值随DQ的增加呈先减小后增大的趋势，随壳低聚糖分子量的增大而增大；CHPDMDHA-g-CACTSs对大肠埃希氏杆菌的MIC值随DQ的增加或亲水基中壳低聚糖分子量的增大呈先减小后增大的趋势；ADMDHA-g-LWCTSs对绿脓杆菌、产气肠杆菌和大肠埃希氏杆菌有较好的抑制作用，且其MIC值随壳低聚糖分子量的增加呈先减小后增大的趋势，随DQ的增大而减小；ADMDHA-g-N-CMC和ADMDHA-g-N-CEC对产气肠杆菌、肺炎克雷伯氏菌、大肠埃希氏杆菌和金黄色葡萄球菌的抑制效果较好，且其抑菌能力随DQ的增加而增强，随壳低聚糖分子量的增加呈先增强后减弱的趋势。采用MTT比色法测定了CHPDMDHA、 ADMDHA、 CA-CTS、CHPDMDHA-g-LWCTSs、 CHPDMDHA-g-CACTSs、 ADMDHA-g-LWCTSs和ADMDHA-g-CACTSs对肺癌H460细胞、乳腺癌MCF7细胞、肝癌SMMC7721细胞和胃癌MKN45细胞的半数抑制浓度(IC50)。结果表明，CHPDMDHA-g-CACTSs3000对4种肿瘤细胞的生长有一定的抑制作用。其中CHPDMDHA-g-N-CMC3000对胃癌MKN45细胞、 CHPDMDHA-g-N,O-CMC3000对肝癌SMMC7721细胞、CHPDMDHA-g-N,O-CEC3000对肝癌SMMC7721细胞和胃癌MKN45细胞的IC50均小于100μg/mL；ADMDHA-g-N-CEC3000对乳腺癌MCF7细胞、肝癌SMMC7721细胞和胃癌MKN45细胞具有一定的杀伤作用，其IC50分别为75.99、62.69、99.93μg/mL；ADMDHA对肺癌H460细胞、乳腺癌MCF7细胞、肝癌SMMC7721细胞和胃癌MKN45细胞的IC50分别为7.10、10.00、4.91、5.63μg/mL，CHPDMDHA对胃癌MKN-45细胞的IC50为9.45μg/mL，说明ADMDHA和CHPDMDHA在体外对这些受试肿瘤细胞具有较好杀伤抑制作用。更多还原

【Abstract】 Polymeric surfactants are the macromolecular compound with surface activities and theirmolecular weight is over from several thousand to tens of thousands. They have attracted moreand more attentions because they have the properties of both macromolecular compound andsurfactant.CHPDMDHA and ADMDHA were synthesized for the first time withdehydroabietylamine as basic material. The quaterary modifications of LWCTSs, N-CMC,N,O-CMC, N-CEC and N,O-CEC with CHPDMDHA and ADMDHA as active quaternaryammonium salt were put forward innovatively. Four series of rosin modified chitosancomb-like polymeric surfactants involving CHPDMDHA-g-LWCTSs,CHPDMDHA-g-CACTSs, ADMDHA-g-LWCTSs and ADMDHA-g-CACTSs were obtainedrespectively. The products were characterized by FT-IR, NMR and elemental analysis.Meanwhile, the surface activity, emulsifying ability, antibacterial activities and antitumoractivities in vitro were also investigated for the synthesized compound. The relationshipsbetween the performance and the structure were discussed preliminarily. It is expected that theresearch results could play a guiding role for the development of polymeric ionic surfactantsbased on rosin and chitosan.The surface activities of CHPDMDHA, ADMDHA and rosin modified chitosan comb-likepolymeric surfactant were estimated by hanging plate method. The results showed thatCHPDMDHA, ADMDHA and rosin modified chitosan comb-like polymeric surfactant alldisplayed good surface activities. The surface activities of CHPDMDHA is better than that ofthe C12~C16alkyl dimethyl benzyl ammonium chloride which has the similar structure withCHPDMDHA. The surface activity of ADMDHA is also better than that of the C16or C18alkyl dimethyl allyl ammonium chloride which has the similar structure with ADMDHA.Thecritical micelle concentration (cmc) of rosin modified chitosan comb-like polymeric surfactants obtained in our investigation were varied from0.75×10-4mol/L to7.31×10-2mol/L, andincreased with the increase of molecular weight (Mw) of LWCTS and decreased with theincrease of quaternary degree (DQ). Their surface tensions at cmc (γcmc) in aqueous solutionwere varied from31.4mN/m to39.4mN/m and decreased with the increase of the Mw ofLWCTS or the DQ.The influences of CHPDMDHA, ADMDHA, and rosin modified chitosan comb-likepolymeric surfactant on the emulsion stability based on paraffin-water system wereinvestigated respectively. The results showed that the emulsifying ability of CHPDMDHA isbetter than that of the C12~C16alkyl dimethyl benzyl ammonium chloride and the emulsifyingability of ADMDHA is also better than that of the C16or C18alkyl dimethyl allyl ammoniumchloride. The emulsification time of CHPDMDHA-g-LWCTSs, CHPDMDHA-g-CACTSs,ADMDHA-g-LWCTSs and ADMDHA-g-CACTSs were extended with the increase of the DQor Mw of LWCTS.The minimum inhibition concentrations (MICs) of CHPDMDHA, ADMDHA, CA-CTS,CHPDMDHA-g-LWCTSs, CHPDMDHA-g-CACTSs, ADMDHA-g-LWCTSs andADMDHA-g-CACTSs against Pseudomonas aeruginosa, Escherichia aerogenes, Klebsiellapneumonia, Escherichia coil, Staphylococcus aureus, and Staphylococcus epidermidis wereestimated by the2-fold agar dilution method. The relationship between the product’santibacterial activities and their structure were investigated preliminarily. The results showedthat CHPDMDHA and ADMDHA could exhibit obvious inhibitory effects on Staphylococcusaureus and Staphylococcus epidermidis, their MICs were16, and64,8and8μg/mL,respectively. The CA-CTSs could behaviour a good antibacterial activity against Escherichiacoil, Staphylococcus epidermidis, and Pseudomonas aeruginosa and their antibacterialactivities against these bateria declined declined with the increase of their degree ofsubstitution (DS) or the molecule weight. The CHPDMDHA-g-LWCTSs could exhibit moreobvious inhibitory effects against Pseudomonas aeruginosa, their MICs tended to decrease atbegin and then increase with the increasing of DQ and to increase with the increase of Mw of LWCTS. The MICs of CHPDMDHA-g-CACTSs against Escherichia coil tended to decrease atbegin and then increase with the increasing of DQ or Mw of LWCTSs contained in thehydrophilic group. The ADMDHA-g-LWCTSs could behave more obvious inhibitory effectsagainst Pseudomonas aeruginosa, Escherichia aerogenes, and Escherichia coil, their MICsdecreased at begin and then increased with the increase of Mw of LWCTSs, and decreased withthe increasing of the DQ. The ADMDHA-g-N-CMC and ADMDHA-g-N-CEC could exhibit agood inhibitory effect against Escherichia aerogenes, Klebsiella pneumonia, Escherichia coil,and Staphylococcus aureus, their antibacterial activities strengthened with the increasing of DQand tended to increase at begin and then decrease with the increase of Mw of LWCTS.The half inhibitory concentration (IC50) of CHPDMDHA, ADMDHA, CA-CTS,CHPDMDHA-g-LWCTSs, CHPDMDHA-g-CACTSs, ADMDHA-g-LWCTSs andADMDHA-g-CACTSs against human lung cancer H460cells, breast cancer MCF7cells,hepatoma SMMC7721cells and gastric cancer MKN45cells were estimated by MTT method.The research results showed that CHPDMDHA-g-CACTSs3000displayed extensive antitumoractivities against the tested tumor cells. The IC50of CHPDMDHA-g-N-CMC3000againstgastric cancer MKN45cells, CHPDMDHA-g-N,O-CMC3000against hepatoma SMMC7721cells, and CHPDMDHA-g-N,O-CEC3000against hepatoma SMMC7721cells and gastriccancer MKN45cells were all lower than100μg/mL. The ADMDHA-g-N-CEC3000couldbehave some antimuor activities against breast cancer MCF7cells, hepatoma SMMC7721cellsand gastric cancer MKN45cells and its IC50against these cancer cells were75.99,62.69, and99.93μg/mL, respectively. The IC50of ADMDHA against lung cancer H460cells, breastcancer MCF7cells, hepatoma SMMC7721cells and gastric cancer MKN45cells were7.10,10.00,4.91and5.63μg/mL, respectively; the IC50of CHPDMDHA against gastric cancerMKN45cells was9.45μg/mL, these data indicated they could display better antitumoractivities in vitro against these tested tumor cells.更多还原