CN106117425A - 烷氧醚基和醛基修饰的聚苯乙炔衍生物及其制备方法 - Google Patents
烷氧醚基和醛基修饰的聚苯乙炔衍生物及其制备方法 Download PDFInfo
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Abstract
本发明涉及烷氧醚基和醛基修饰的聚苯乙炔衍生物及其制备方法,该衍生物的结构式为:本发明采用烷氧醚基(OEG)构建聚苯乙炔,赋予了聚苯乙炔优异的温敏性能,相变过程迅速,滞后小;通过动态席夫碱键传递手性至共聚物主链,从而有效而可逆地调控聚合物主链的构象;拓宽了聚苯乙炔在水相高效识别氨基酸类手性分子的应用。
Description
技术领域
本发明涉及一类聚苯乙炔衍生物及其制备方法,特别是一类烷氧醚基和醛基修饰的聚苯乙炔衍生物及其制备方法。
背景技术
螺旋性是生物大分子的重要结构特征,很多生物功能是通过这类天然大分子螺旋构象形成的多级结构得以实现,如多肽表面有序的螺旋结构使得氨基酸侧基能够有序排列,从而进行分子识别;细菌体内吸光蛋白的螺旋结构则保证了蛋白固有的刚性及明确的结合位点,使得色素分子进行有序的分布;核苷酸以双螺旋的形式储存和复制生命信息等等。因而发展和研究仿生螺旋聚合物具有重要学术价值。
聚苯乙炔作为一类人工合成的动态螺旋聚合物,由于其主链左右手螺旋翻转位垒较低,微小的手性差异便可导致主链构象发生很大的改变,这类螺旋化合物近年来受到更加广泛的关注,并应用于制备刺激响应型聚合物。通常而言,其主链的螺旋构象可以通过在侧链或者端基引入手性基元,有效诱导聚苯乙炔形成特定的螺旋结构,并且这种聚合物的二级结构可以通过改变外界条件,温度、溶剂及酸碱度等进行调控:如唐本忠等人[Lai, L.M.; Jackey, W. Y.; Qin, A.; Dong, Y.; Tang, B. T. J. Phys. Chem. B, 2006,110, 11128.]合成出带有天然氨基酸侧基的螺旋手性聚苯乙炔, 并通过改变溶液酸碱度来调控其螺旋性;Masuda等人[Zhang, Y.; Gao, K.; Zhao, Z.; Yue, D.; Hu, Y.;Masuda, T.J. Polym. Sci., Part A, Polym. Chem., 2013, 51, 5248.]合成了一系列的带手性侧基的聚丙炔酰胺,通过共轭骨架和功能侧基之间的协同作用, 聚乙炔表现出了一系列有趣的性质: 光学活性、液晶性、光电导性、溶剂化显色以及分子识别等。Meijer[Schenning A. P. H. J., Fransen M., Meijer E. W. Macromol. Rapid Commun.,2002, 23, 265.]和Percec [Percec V., Obata M., Rudick J G., De B. B., GloddeM., Bera T., Magonov S N., Balagurusamy V. S. K., Heiney P A. Polym. Sci., Part A: Polym. Chem., 2002, 40, 3509.]等人分别报道聚苯乙炔及其衍生物在升温过程中,由于有效共轭链长和构象的变化,主链的圆二色谱信号会有所降低和红移。
根据手性基元与螺旋聚合物主链的成键方式不同,可分为两类,共价型和非共价型。共价型螺旋聚合物是通过大单体法制得带有手性侧基,进而聚合物得到二级结构规整的螺旋聚合物;Yashima等人通过超分子—主客体络合方式,成功实现小分子手性向主链传递,进而赋予该类螺旋聚合物对D/L构型丙氨酸的识别功能[Nonokawa, R.; Yashima, E.J. Am. Chem. Soc.,2003, 125, 1278]。
氨基酸作为人体生命组成最重要的手性源,对其识别研究在手性拆分、生物传感器以及贮能等不同领域的广阔应用前景而受到高度重视。利用氨基酸识别来构筑螺旋聚合物对于阐述生命体过程具有其独特的优势。
发明内容
本发明的目的之一在于提供一类烷氧醚基(OEG)和醛基修饰的聚苯乙炔衍生物,用于氨基酸的识别,以及识别前后对于聚合物螺旋构象的诱导调控。
本发明的目的之二在于提供该聚合物的制备方法。
动态键较超分子作用,既有共价键成键稳定的特性,又兼具非共价键的动态可逆特性。且通过非共价键---动态共价键构筑螺旋聚苯乙炔鲜为报道。
为了实现以上发明目的,本发明采用如下反应机理:
根据上述反应机理,本发明采用如下技术方案:
一种烷氧醚基和醛基修饰的聚苯乙炔衍生物,其特征在于该衍生物的结构式为:
其中共聚比为m:n = 1~4:1
一种烷氧醚基和醛基修饰的聚苯乙炔衍生物,其特征在于该方法的具体步骤为:
a.将对醛基苯乙炔和L-苯丙氨酸甲酯按1:1~2的摩尔比溶于二氯甲烷中,搅拌反应3~6小时;旋干DCM,对粗产物进色谱柱提纯,即可得到单体PP,其结构式为:;
b.将4-碘代苯甲酸乙酯、碘化亚铜、Pd(Pph3)2Cl2和TMSA(三甲基硅基乙炔)按 1:0.04~0.08:0.02~0.04:1.0~1.5的摩尔比溶于四氢呋喃中,在惰性气氛保护下,搅拌反应12~18小时;去除溶剂,用二氯甲烷萃取,再经色谱柱提纯,得到纯产物C,其结构式为: ;
c.将步骤b所得产物C溶于乙醇中,在冰浴下,滴加氢氧化钠水溶液,搅拌反应1~4小时;调节溶液pH值至中性,用二氯甲烷萃取,抽滤,得纯产物D;所述的产物C与氢氧化钠的摩尔比为:1:1~2;
d.将步骤c所得产物D、核心为氨基的一代烷氧醚树枝化基元和DMAP(4-二甲氨基吡啶)按1~1.5:1:0.2~0.5的摩尔比溶于二氯甲烷中, 在冰盐浴和惰性气体保护下,加入HOBt(1-羟基苯并三唑)和EDC·HCl(1-乙基-(3-二甲基氨基丙基)碳化二亚胺盐酸盐),室温下继续搅拌至反应完全;饱和食盐水水洗后,用二氯甲烷萃取水相,无水MgSO4干燥有机相,去除溶剂后得粗产物,对该粗产物进行色谱柱分离提纯得到单体PN;所述的产物D、HOBt和EDC·HCl的摩尔比为:1:0.8~1.5:1~5;(参照文献Li, W.; Zhang, A.; Schlüter, A. D. Chem. Commun. 2008, 5523和Yan J T; Li W; Liu K; Wu D L; Chen F;Wu P Y; Zhang A.Chem. Asian J. 2011, 6, 3260的合成);
e.在惰性气氛保护下,将步骤a所得单体PP和步骤d所得单体PN(按照共聚比为m:n = 1~4:1)溶于四氢呋喃中,加入催化量的Rd(nbd)Cl2和三乙胺;在室温下反应9~16小时;去除四氢呋喃得粗产物,对该粗产物进行色谱柱分离提纯得到聚合物烷氧醚基和醛基修饰的聚苯乙炔衍生物。
所述的聚苯乙炔衍生物,其制备方法包括步骤:Sonogashira偶联、脱保护、醚化、酯化、酰胺、动态席夫碱等反应合成了三种苯乙炔类单体,通过控制单体的投料比,在THF中采用[(nbd)RhCl]2催化聚合得到了烷氧醚基不同键联方式(酰胺键和酯键)且醛基比例不同的聚苯乙炔衍生物。
所述的聚苯乙炔衍生物具有良好的水溶性,其优异的温敏性能表现为相变迅速;通过动态席夫碱键,将手性从侧链传递至聚苯乙炔主链,从而实现对主链手性放大及构象调控;同时此类聚苯乙炔衍生物对氨基酸有良好的识别能力。
该类聚苯乙炔共聚物在具有温敏性的同时,通过聚合物链上醛基与氨基酸的动态反应,一方面可调控聚合物主链构象,也赋予该类聚合物对氨基酸高效识别特性(灵敏度可达10-4-10-5)。这类全新型智能螺旋聚苯乙炔衍生物,为模拟生命体过程,阐述生命过程的化学本质具有重要理论意义。
本发明基于“将军士兵”原理,通过大单体和表面接枝路线,成功地实现了该类聚合物对氨基酸的有效识别;同时提出了一种新型方式--动态键,将小分子手性向聚合物有效的传递,并诱导其主链二级构象的变化。这类共聚物中含有烷氧醚基(OEG)和带有氨基酸(L-Phe-CooMe)修饰的苯甲醛基元/ 苯甲醛基元,在赋予聚合物温度敏感智能性外;另一方面,提供聚合物侧链手性传递位点。圆二色光谱测试表明,识别位点的比例、烷氧醚基元与聚合物的键联方式、待识别氨基酸亲疏水性结构等等,都对该类聚合物识别起着重要的贡献;此外,通过大单体法制备的螺旋聚合物,可以通过时间、pH、手性分子、温度等外界刺激条件,实现对此类聚合物二级构象的调控。该发明对于设计并合成不同螺旋结构的聚合物并使其功能化提供理论基础,在制备新型仿生与功能材料方面具有重要学术价值,为拓展刺激响应型螺旋聚合物在手性拆分、生物传感器及储能等不同领域中的应用具有指导意义。
本发明与现有技术相比较,具有如下显而易见的突出实质性特点和显著优点:
1. 本发明采用烷氧醚基(OEG)构建聚苯乙炔,赋予了聚苯乙炔优异的温敏性能,相变过程迅速,滞后小;
2. 本发明通过动态席夫碱键传递手性至共聚物主链,从而有效而可逆地调控聚合物主链的构象;
3. 本发明制备了一种水溶性的聚苯乙炔,拓宽了聚苯乙炔在水相高效识别氨基酸类手性分子的应用。
附图说明
图1 合成聚合物NG1-0.26Phe和NG1-0.26CHO的合成路线;
图2 为聚合物NG1-0.26Phe和NG1-0.26CHO的核磁氢谱表征(氯仿25 °C,500M);
图3 为NG1-0.26CHO和NG1-0.26Phe在水溶液中溶液透光率随温度变化曲线(c = 0.05wt %, 600 nm, 加热和冷却速率0.2 oC/min);
图4-8 为NG1-0.26CHO和NG1-0.26Phe的圆二色光谱图。
具体实施方式
下面结合具体实例对本发明作进一步阐述,但这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解,在阅读了本发明阐述的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
对醛基苯乙炔的制备方法 请参见参照文献Zhang, Y.; Gao, K.; Zhao, Z.;Yue, D.; Hu, Y.; Masuda, T.J. Polym. Sci., Part A, Polym. Chem., 2013, 51,5248。
核心为氨基的一代烷氧醚树枝化基元(G1-CH2NH2)的制备请参见参照文献Li, W.;Zhang, A.; Schlüter, A. D. Chem. Commun. 2008, 5523和Yan J T; Li W; Liu K; WuD L; Chen F;Wu P Y; Zhang A. Chem. Asian J. 2011, 6, 3260的合成。
实施例1:
1.单体的合成
单体PP
(a)4-溴苯甲醛溶于四氢呋喃(THF),加入0.04~0.08倍当量碘化亚铜(CuI),0.02~0.04倍当量Pd(Pph3)2Cl2,1.0~1.5倍当量三甲基硅基乙炔(TMSA)溶于少量四氢呋喃后缓慢加入,氮气保护下搅拌反应12~18 h;旋干THF, 二氯甲烷(DCM)萃取,对粗产物进行色谱柱提纯,得纯产物A。
(b)A溶于甲醇(CH3OH)中,加入1.0~2.5倍当量的碳酸钾(K2CO3)溶于少量水,在冰浴中缓慢滴加,搅拌反应2~5 h;用盐酸(HCl)将溶液调至中性,旋干CH3OH, DCM萃取,DCM对粗产物进行色谱柱提纯,得纯产物B。
(c)B溶于DCM中,加入1~2倍当量的L-苯丙氨酸甲酯(L-Phe-CooMe),搅拌反应3~6h;旋干DCM,对粗产物进行色谱柱提纯,得到单体PP。
单体PN
(d)4-碘代苯甲酸乙酯溶于THF,加入0.04~0.08倍当量碘化亚铜(CuI),0.02~0.04倍当量Pd(Pph3)2Cl2,1.0~1.5倍当量TMSA溶于少量四氢呋喃后缓慢加入,氮气保护下搅拌反应12~18 h;旋干THF, DCM萃取,Hexane对粗产物进行色谱柱提纯,得纯产物C。
(e)C溶于乙醇(EtOH)中,加入1~2倍当量的氢氧化钠(NaOH)溶于少量水,在冰浴中缓慢滴加,搅拌反应1~4 h;用盐酸(HCl)将溶液调至中性,旋干甲醇,二氯甲烷(DCM)萃取,抽滤,得纯产物D。
(f)将1~1.5倍当量D溶于DCM, 加入1倍当量的核心为氨基的一代烷氧醚树枝化基元(G1-CH2NH2),(参照文献Li, W.; Zhang, A.; Schlüter, A. D. Chem. Commun. 2008,5523和Yan J T; Li W; Liu K; Wu D L; Chen F;Wu P Y; Zhang A. Chem. Asian J.2011, 6, 3260的合成),0.2~0.5倍当量DMAP溶于DCM, 冰盐浴氮气保护下加入0.8~1.5当量HOBt,加入1~5当量EDC·HCl, 室温下继续搅拌至反应完全;饱和食盐水水洗后DCM萃取水相,无水MgSO4干燥有机相,旋干DCM后,DCM对粗产物进行色谱柱提纯得到单体PN。
2.聚合物NG1-0.26Phe的合成
将单体1和3(按照共聚比为m:n = 1~4:1)溶于少量THF中,氮气保护下,加入1/50当量Rd(nbd)Cl2、 三乙胺(TEA)1滴。25℃下反应9~16 h;旋干THF后,DCM对粗产物进行色谱柱提纯得到聚合物NG1-0.26Phe。由附图1 1H NMR (CDCl3, 25 oC): d = 0.98−1.36 (m, 9H,CH3), 3.07-4.48 (br, 42H, CH2), 5.01-8.98 (br, 1H, CH2, Ar-H)。可知证明得到了目标产物。
3.聚合物NG1-0.26CHO的合成
聚合物NG1-0.26Phe溶于DCM,加入50~200倍当量的三氟乙酸(TFA),搅拌反应1~5 h;加入过量的CH3OH终止反应,旋干甲醇,在水中透析,冷冻干燥,得到产物。由附图2 1H NMR(CDCl3, 25 oC): d = 1.02−1.25 (br, 9H, CH3), 3.08-4.25 (br, 42H, CH2), 4.91−8.81 (m, 38H, CH2), 9.59 (s, 1H, CH)。可知证明得到了目标产物。
实施例2:
通过圆二色光谱对聚合物NG1-0.26Phe、NG1-0.26CHO的螺旋结构进行了表征(参见图4到图8)。如附图4所示,在常温下(20 oC),带有手性侧基的NG1-0.26Phe有较为规整的构象,在CD上显示较强的信号峰;对于没有手性基元诱导的NG1-0.26CHO,聚合物主链表现为左手右手螺旋构象交替,其CD信号峰消失;当在NG1-0.26CHO加入手性基元L-Phe,聚合物的在CD上表现与NG1-0.26Phe相反的科顿信号,且信号强度增加。由此证明,通过大单体及表面接枝路线,都能实现动态键(席夫碱)方式,将小分子手性从侧链向主链的传递。
附图5-7所示,时间、溶剂及手性分子等因素,都影响NG1-0.26Phe的二级构象。随着时间的推移,NG1-0.26Phe的螺旋结构从左手偏向右手转变;在聚合物体系中 ,引入L构型的氨基酸,同样会诱导主链的构型翻转;同时此类聚合物的构象也受到溶剂化效应的影响。
根据上述研究结果表明,在聚合物NG1-0.26CHO加入手性基元,诱导聚合物主链呈现较为规整的结构,从而在圆二色光谱图上表现出较强的科顿信号。附图8所示,利用聚合物NG1-0.26CHO对于手性基元的响应,我们尝试在该类聚合物中加入D/L不同构型、侧链亲疏水差异及侧链由较大位阻基团修饰的氨基酸。经过测试表明,加入手性氨基酸构型的差异导致聚合物正负科顿信号翻转;侧链由较疏水基团修饰的氨基酸(相比亲水性氨基酸)与聚合物NG1-0.26CHO反应后,更利于形成较为稳定的螺旋构象(即较强的科顿信号),尤其是以D/L-Phe为代表的(侧基由苯环这类较大位阻基团修饰)氨基酸,形成的科顿信号最强,且识别灵敏度可达10-4-10-5。
Claims (2)
1.一种烷氧醚基和醛基修饰的聚苯乙炔衍生物,其特征在于该衍生物的结构式为:
其中共聚比为m:n =(1~4):1。
2.一种制备根据权利要求1所述的烷氧醚基和醛基修饰的聚苯乙炔衍生物,其特征在于该方法的具体步骤为:
a.将对醛基苯乙炔和L-苯丙氨酸甲酯按1:(1~2)的摩尔比溶于二氯甲烷中,搅拌反应3~6小时;旋干DCM,对粗产物进色谱柱提纯,即可得到单体PP,其结构式为:
;
b.将4-碘代苯甲酸乙酯、碘化亚铜、Pd(Pph3)2Cl2和三甲基硅基乙炔TMSA按 1:(0.04~0.08):(0.02~0.04):(1.0~1.5)的摩尔比溶于四氢呋喃中,在惰性气氛保护下,搅拌反应12~18小时;去除溶剂,用二氯甲烷萃取,再经色谱柱提纯,得到纯产物C,其结构式为:
;
c.将步骤b所得产物C溶于乙醇中,在冰浴下,滴加氢氧化钠水溶液,搅拌反应1~4小时;调节溶液pH值至中性,用二氯甲烷萃取,抽滤,得纯产物D;所述的产物C与氢氧化钠的摩尔比为1:(1~2);
d.将步骤c所得产物D、核心为氨基的一代烷氧醚树枝化基元和4-二甲氨基吡啶DMAP按1~(1.5:1):(0.2~0.5)的摩尔比溶于二氯甲烷中, 在冰盐浴和惰性气体保护下,加入1-羟基苯并三唑HOBt和1-乙基-(3-二甲基氨基丙基)碳化二亚胺盐酸盐EDC·HCl,室温下继续搅拌至反应完全;饱和食盐水水洗后,用二氯甲烷萃取水相,无水MgSO4干燥有机相,去除溶剂后得粗产物,对该粗产物进行色谱柱分离提纯得到单体PN;所述的产物D、HOBt和EDC·HCl的摩尔比为:1:(0.8~1.5):(1~5);
e.在惰性气氛保护下,将步骤a所得单体PP和步骤e所得单体PN按照共聚比为m:n= 1~4:1的比例溶于四氢呋喃中,加入催化量的Rd(nbd)Cl2和三乙胺;在室温下反应9~16小时;去除四氢呋喃的粗产物,对该粗产物进行色谱柱分离提纯得到聚合物烷氧醚基和醛基修饰的聚苯乙炔衍生物。
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CN111825800B (zh) * | 2020-06-08 | 2023-02-10 | 上海大学 | 具有自组装特性的螺旋聚苯乙炔衍生物、组装体及其制备方法 |
CN113717317A (zh) * | 2021-08-09 | 2021-11-30 | 浙江理工大学 | 一种负载金属离子的单手性螺旋共聚取代聚炔及其制备方法和应用 |
CN113717317B (zh) * | 2021-08-09 | 2023-06-27 | 浙江理工大学 | 一种负载金属离子的单手性螺旋共聚取代聚炔及其制备方法和应用 |
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