CN107099028A - 一种聚肌氨酸嵌段共聚物的制备方法 - Google Patents
一种聚肌氨酸嵌段共聚物的制备方法 Download PDFInfo
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Abstract
本发明公开了一种聚肌氨酸嵌段共聚物的制备方法,属于高分子材料技术领域,首先以RAFT试剂控制亲水性乙烯基单体RAFT聚合反应,生成第一嵌段亲水聚乙烯基聚合物;然后去除聚合物末端硫代羰基硫基团,释放保护的氨基作为大分子引发剂,引发N‑甲基取代甘氨酸‑N‑羧基酸酐开环聚合生成双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物。本发明是一种一锅法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物的方法,该方法工艺简便、成本低廉、反应速率高效。
Description
技术领域
本发明属于高分子材料技术领域,具体涉及一锅法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物的方法。
背景技术
双亲性嵌段共聚物由可溶于水的、化学性质不同的嵌段聚合物组成,在药物和基因传输、催化、表面改性以及形成无机纳米晶体模板化等领域有很大的应用前景。双亲性嵌段共聚物具有完全的水溶性,“智能”自组装行为,与底物相互作用的能力,而且是潜在的环境友好和生物相容性的替代品,因而越来越受到科研人员的广泛关注并被深入研究。
聚乙二醇为基础的双亲性嵌段共聚物,在生物医药等领域得到了深入研究并被广泛应用,通常认为聚乙二醇是相对良性和免疫安全的亲水聚合物。然而,近期的实验研究表明,以聚乙二醇为基础的载体在体内的使用过程中表现出一些缺点,如:免疫反应(Macromolecules,2015,48(6),1673)、非生物降解性(Macromolecular RapidCommunications 2014,35(22),1954)等,这些缺点在一定程度上限制了聚乙二醇作为医用载体在临床上的应用。为了克服这些缺点,我们选择了一种生物相容的、生物可降解的、亲水的聚合物聚肌氨酸,作为聚乙二醇的替代物,合成双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物。这类双亲性嵌段共聚物具有聚乙二醇为基础双亲性嵌段共聚物的性能,克服了聚乙二醇的非生物降解性和人体中免疫反应的缺点。
在过去十几年中,将RAFT(reversible addition-fragmentation chaintransfer)聚合和开环聚合相结合制备嵌段共聚物的研究很多,比如,Macromolecules2013,46,1291-1295;Macromolecules 2012,45(1),87-99;Macromolecules 2011,44(6),1347-1354等等,但是还没有研究过将亲水性乙烯基单体的RAFT聚合和亲水的N-甲基取代甘氨酸-N-羧基酸酐单体的开环聚合相结合制备双亲性嵌段共聚物。因此寻找一种操作简便、具体可行的方法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物十分必要。
发明内容
本发明的目的在于提供一种一锅法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物的方法,该方法工艺简便、成本低廉、反应速率高效。
本发明提供的一锅法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物的方法,首先以结构如(Ⅰ)所示的RAFT(reversible addition-fragmentation chain transfer)试剂控制亲水性乙烯基单体RAFT聚合反应,生成第一嵌段亲水聚乙烯基聚合物;然后去除聚合物末端硫代羰基硫基团,释放保护的氨基作为大分子引发剂,引发N-甲基取代甘氨酸-N-羧基酸酐开环聚合生成双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物。为了表述方便,所述的亲水性乙烯基单体如式(II)所示,上述的反应步骤如下所示
RAFT聚合反应
大分子引发剂反应过程
以上制备双亲性嵌段共聚物的方法中,所述的亲水性乙烯基单体分为两类,高活性亲水乙烯基单体和低活性亲水乙烯基单体,所述的高活性亲水乙烯基单体结构如式(III)所示,此时X为R3,Y为
其中,R3为氢或甲基;R1、R2是选自氢,具有1~5个碳原子的直链或支链烷基,具有1~5个碳原子的直链或支链羟基,具有1~5个碳原子的直链或支链羧基,具有3~5个碳原子的环烷基,具有3~5个碳原子的环烷基被卤原子、烷氧基、羟基或羧基中的一种或多种所取代;
低活性亲水乙烯基单体结构如式(IV)所示,此时X为氢,Y为
n为2~10,优选n为2~4。
高活性亲水乙烯基单体为丙烯酰胺类和甲基丙烯酰胺类,结构如式(V)、(VI)所示:
其中,R1、R2是选自氢、甲基、乙基、丙基、异丙基、正丁基、叔丁基、正戊基中的相同或不同基团;其中上述基团可被羟基、羧基取代。
所述的乙烯基单体RAFT聚合反应是在60℃~80℃条件下进行,聚合反应时间为2~40小时。
所述的去除聚合物末端硫代羰基硫基团,释放保护的氨基是在乙烯基聚合物反应液中直接连续反应,反应过程如下所示:
其中,m为乙烯基聚合物的聚合度;
去除聚合物末端硫代羰基硫基团的方法为偶氮二异丁腈与第一嵌段亲水聚乙烯基聚合物在温度范围为60℃~90℃下反应4h~10h,偶氮二异丁腈与RAFT试剂的摩尔比为20:1~30:1;
氨基脱保护的方法为将水合肼加入到反应液中在温度范围为60℃~70℃下反应0.5h~3h得到大分子引发剂,水合肼与RAFT试剂的摩尔比为10:1~50:1。
去除聚合物末端硫代羰基硫基团,释放保护的氨基反应,是为了使乙烯基聚合物末端带有一个氨基作为大分子引发剂,去除聚合物末端硫代羰基硫基团反应是防止硫代羰基硫会与脱保护的氨基反应,而与后面的开环聚合反应没有影响,只要去除硫代羰基硫基团后生成的基团不与氨基反应,不引发开环聚合反应。
所述的N-甲基取代甘氨酸-N-羧基酸酐单体结构如式(Ⅶ)所示:
N-甲基取代甘氨酸-N-羧基酸酐单体与大分子引发剂的摩尔比为20:1~300:1。
所述的大分子引发剂引发N-甲基取代甘氨酸-N-羧基酸酐单体开环聚合反应温度为室温,聚合反应时间为2~6小时。
所述的溶剂为乙腈、二氧六环、N,N-二甲基甲酰胺、甲苯或苯中的一种。
所述高活性亲水丙烯酰胺类单体结构如编号1~12所示,高活性亲水甲基丙烯酰胺类单体结构如编号13~21所示,低活性亲水乙烯基单体结构如编号22~24所示:
有益效果
本专利中采用一种工艺简便、成本低廉、反应速率高效的方法制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物。聚肌氨酸具有生物相容性、生物可降解性,在生物医药领域有很大应用潜力,用聚肌氨酸作为聚乙二醇的替代物,可以克服聚乙二醇免疫反应、非生物降解性的缺点,合成的双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物在生物医药领域比聚乙二醇为基础的双亲性嵌段共聚物更有优势。
本专利使用一锅法连续反应制备双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物,该方法消除了中间聚合物析出步骤,简化了反应工艺流程,而且反应快速,过程可控,反应条件温和,得到的嵌段共聚物分子量可控,分子量分布窄。
具体实施方式
通过下列实施例可以进一步说明本发明,实施例是为了说明而非限制本发明的。本领域的任何普通技术人员都能够理解这些实施例不以任何方式限制本发明,可以对其做适当的修改和数据变换而不违背本发明的实质和偏离本发明的范围。
实施例1
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-乙基丙烯酰胺(1.983g,20mmol),偶氮二异丁腈(0.033g,0.2mmol),8mL的无水苯,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,60℃反应2h,转化率97%。将三正丁基氢锡(11.6g,40mmol),偶氮二异丁腈(0.033g,0.2mmol),1mL的无水苯混合成溶液,用注射器加入到反应瓶中,70℃反应3h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(2.3g,20mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为20:1,在持续通氮气流条件下室温反应2h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-乙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)4.32g,转化率98%。聚(N-乙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为4400g/mol,分子量分布PDI为1.12。
实施例2
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-丙基丙烯酰胺(5.658g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率95%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)10.08g,转化率97%。聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为11000g/mol,分子量分布PDI为1.11。
实施例3
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-丙基丙烯酰胺(16.974g,150mmol),偶氮二异丁腈(0.033g,0.2mmol),60mL的无水甲苯,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应4h,转化率96%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水甲苯混合成溶液,用注射器加入到反应瓶中,80℃反应8h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应2h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应5h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)21.15g,转化率97%。聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为20800g/mol,分子量分布PDI为1.13。
实施例4
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-异丙基丙烯酰胺(5.658g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水N,N-二甲基甲酰胺,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,60℃反应2h,转化率97%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水N,N-二甲基甲酰胺混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(17.264g,150mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为150:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-异丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)20.08g,转化率98%。聚(N-异丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为20400g/mol,分子量分布PDI为1.14。
实施例5
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N,N-二乙基-2-丙烯酰胺(6.360g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率97%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(34.527g,300mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为300:1,在持续通氮气流条件下室温反应6h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N,N-二乙基-2-丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)36.25g,转化率96%。聚(N,N-二乙基-2-丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为37200g/mol,分子量分布PDI为1.15。
实施例6
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-(2-羟丙基)甲基丙烯酰胺(7.160g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率97%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-(2-羟丙基)甲基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)11.23g,转化率97%。聚(N-(2-羟丙基)甲基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为12000g/mol,分子量分布PDI为1.12。
实施例7
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-乙烯基吡咯烷酮(5.557g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,80℃反应30h,转化率96%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-乙烯基吡咯烷酮)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)10.78g,转化率97%。聚(N-乙烯基吡咯烷酮)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为10100g/mol,分子量分布PDI为1.16。1H NMR(300MHz,DMSO-d6):δ(ppm)=2.66-3.14(3H,–N(CH3)–),3.96-4.47(2H,–N(CH3)CH2CO–),3.33-3.72(1H,–CH2CH–),2.92-3.27(2H,–CH2NCO–),2.03-2.47(2H,–CHNCOCH2–),1.76-2.0(2H,–NCH2CH2CH2CO–),1.33-1.75(2H,–CH2CHN–)。
实施例8
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-乙烯基己内酰胺(6.960g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应40h,转化率98%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-乙烯基己内酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)11.33g,转化率97%。聚(N-乙烯基己内酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为11300g/mol,分子量分布PDI为1.13。
实施例9
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-丙基丙烯酰胺(33.948g,300mmol),偶氮二异丁腈(0.033g,0.2mmol),120mL的无水二氧六环,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应6h,转化率95%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水二氧六环混合成溶液,用注射器加入到反应瓶中,80℃反应9h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应3h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应6h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)35.36g,转化率96%。聚(N-丙基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为30700g/mol,分子量分布PDI为1.15。
实施例10
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N-(2-羟丙基)丙烯酰胺(6.458g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水二氧六环,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率96%。将过量偶氮二异丁腈(4.93g,30mmol),1mL的无水二氧六环混合成溶液,用注射器加入到反应瓶中,90℃反应4h除去聚合物末端的硫代羰基硫基团。将水合肼(2.5g,50mmol)加入到反应液中,70℃反应0.5h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N-(2-羟丙基)丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)11.33g,转化率98%。聚(N-(2-羟丙基)丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为11000g/mol,分子量分布PDI为1.12。
实施例11
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),N,N-二乙基-2-甲基丙烯酰胺(7.061g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率97%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,60℃反应10h除去聚合物末端的硫代羰基硫基团。将水合肼(0.5g,10mmol)加入到反应液中,70℃反应3h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物聚(N,N-二乙基-2-甲基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)11.13g,转化率96%。聚(N,N-二乙基-2-甲基丙烯酰胺)嵌段聚(N-甲基取代甘氨酸-N-羧基酸酐)的数均分子量Mn为12000g/mol,分子量分布PDI为1.12。
实施例12
在反应瓶中,加入结构如(Ⅰ)所示的RAFT试剂(0.342g,1mmol),结构如编号12所示的单体(7.157g,50mmol),偶氮二异丁腈(0.033g,0.2mmol),20mL的无水乙腈,进行三次冻-抽-融循环出去反应体系中的氧,氮气氛围密封,70℃反应2h,转化率98%。将过量偶氮二异丁腈(3.3g,20mmol),1mL的无水乙腈混合成溶液,用注射器加入到反应瓶中,80℃反应6h除去聚合物末端的硫代羰基硫基团。将水合肼(1g,20mmol)加入到反应液中,60℃反应1h释放聚合物末端氨基。在反应体系通氮气流条件下,将N-甲基取代甘氨酸-N-羧基酸酐(5.755g,50mmol)加入到反应溶液中,单体与大分子引发剂摩尔比为50:1,在持续通氮气流条件下室温反应4h,反应结束后,将反应液滴加到过量***中析出聚合物,真空干燥后得产物11.27g,转化率97%。得到的双亲性嵌段共聚物的数均分子量Mn为12100g/mol,分子量分布PDI为1.12。
Claims (10)
1.一种聚肌氨酸嵌段共聚物的制备方法,其特征在于,
(1)聚合反应:如式(Ⅰ)所示的RAFT试剂与亲水性乙烯基单体进行RAFT聚合反应,生成第一嵌段亲水聚乙烯基聚合物;
(2)开环聚合反应:去除第一嵌段亲水聚乙烯基聚合物末端硫代羰基硫基团,释放保护的氨基作为大分子引发剂,引发如式(Ⅱ)所示的N-甲基取代甘氨酸-N-羧基酸酐开环聚合生成双亲性聚乙烯基嵌段聚肌氨酸嵌段共聚物。
2.根据权利要求1所述的制备方法,其特征在于:所述的亲水性乙烯基单体为高活性亲水乙烯基单体或低活性亲水乙烯基单体两类,所述的高活性亲水乙烯基单体结构如式(III)所示,
其中,R3为氢或甲基;R1、R2是选自氢,具有1~5个碳原子的直链或支链烷基,具有1~5个碳原子的直链或支链羟基,具有1~5个碳原子的直链或支链羧基,具有3~5个碳原子的环烷基,具有3~5个碳原子的环烷基被卤原子、烷氧基、羟基或羧基中的一种或多种所取代;
所述的低活性亲水乙烯基单体结构如式(IV)所示,
n为2-10。
3.根据权利要求2所述的制备方法,其特征在于,所述的高活性亲水乙烯基单体为丙烯酰胺类和甲基丙烯酰胺类,结构如式(V)、(VI)所示:
其中,R1、R2是选自氢、甲基、乙基、丙基、异丙基、正丁基、叔丁基、正戊基中的相同或不同基团;其中上述基团可被羟基、羧基取代;所述的低活性亲水乙烯基单体中n的范围为2~4。
4.根据权利要求2或3所述的制备方法,其特征在于,所述高活性亲水丙烯酰胺类单体结构如编号1~12所示,高活性亲水甲基丙烯酰胺类单体结构如编号13~21所示,低活性亲水乙烯基单体结构如编号22~24所示:
5.根据权利要求1所述的制备方法,其特征在于,所述的乙烯基单体与RAFT试剂的摩尔比为20:1~300:1。
6.根据权利要求1所述的制备方法,其特征在于,所述的乙烯基单体RAFT聚合反应是在60℃~80℃条件下进行,聚合反应时间为2~40小时。
7.根据权利要求1所述的制备方法,其特征在于,所述的去除聚合物末端硫代羰基硫基团的方法为偶氮二异丁腈与第一嵌段亲水聚乙烯基聚合物在温度范围为60℃~90℃下反应4h~10h,偶氮二异丁腈与RAFT试剂的摩尔比为20:1~30:1;
氨基脱保护的方法为将水合肼加入到反应液中在温度范围为60℃~70℃下反应0.5h~3h得到大分子引发剂,水合肼与RAFT试剂的摩尔比为10:1~50:1。
8.根据权利要求1所述的制备方法,其特征在于,所述的N-甲基取代甘氨酸-N-羧基酸酐单体与大分子引发剂的摩尔比为20:1~300:1。
9.根据权利要求1所述的制备方法,其特征在于,所述的大分子引发剂引发N-甲基取代甘氨酸-N-羧基酸酐单体开环聚合反应温度为室温,聚合反应时间为2~6小时。
10.根据权利要求1所述的制备方法,其特征在于,所述的溶剂为乙腈、二氧六环、N,N-二甲基甲酰胺、甲苯或苯中的一种。
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