CN110698449A - 一类新型光敏剂的制备方法及应用 - Google Patents

一类新型光敏剂的制备方法及应用 Download PDF

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CN110698449A
CN110698449A CN201910508273.XA CN201910508273A CN110698449A CN 110698449 A CN110698449 A CN 110698449A CN 201910508273 A CN201910508273 A CN 201910508273A CN 110698449 A CN110698449 A CN 110698449A
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hydroxybenzaldehyde
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李昌华
翟文豪
张永康
张俊青
刘明
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Abstract

本发明涉及一类新型光敏剂的制备方法及其应用,该类光敏剂首次被合成,以中间体式(I)所示通式的化合物为母核,与对羟基苯甲醛、3,5‑二溴‑4‑羟基苯甲醛和3,5‑二碘‑4‑羟基苯甲醛进行Knoevenagel反应,得式(II)所示通式的光敏剂。本发明创造性地在中间体式(I)和光敏剂式(II)上预留官能团(R1、R2),并首次合成了以S、Se为中心原子(Q)的中间体及光敏剂。本发明提供的一类新型光敏剂,解决了现有光敏剂吸收范围窄、可见光范围内治疗效果差、使用光源功率过大、无法引入官能团的技术问题。
Figure DSA0000184446160000011

Description

一类新型光敏剂的制备方法及应用
技术领域
本发明涉及光动力治疗技术领域,具体涉及一类新型光敏剂、制备方法及其应用。
背景技术
光动力治疗(PDT)是以非手术的形式治疗癌症的一种手段。1975年,Dougherty等人首次对其进行论证,并进行了广泛的研究。目前,PDT已成为一种癌症治疗的特殊方式。光动力疗法在光照条件下利用光敏剂吸收光子,达到激发态,通过隙间穿越,将能量传递给三线态氧,并将三线态氧转化为具有细胞毒性的单线态氧(1O2),进而不可逆地杀伤癌细胞,达到治疗癌症的目的。相比于化疗和放疗,光动力疗法无创伤、无毒副作用、可重复治疗。
近年来,光动力疗法虽然已经引起人们的广泛关注,但是在实际应用中,治疗效果并不理想,因此设计一种性能优良的光敏剂对于光动力疗法而言尤为重要。
发明内容
本发明提供了一类新型光敏剂的制备方法及其应用,解决了现有光敏剂吸收范围窄、可见光范围内治疗效果差、使用光源功率过大、无法引入官能团的技术问题。
本发明提供了一类新型光敏剂,具有如式(I)所示的结构式:
Figure RE-GSB0000184749420000011
式(I)和(II)中Q为O或S或Se。
式(I)和(II)中R1为H或
Figure RE-GSB0000184749420000012
R2为H或
Figure RE-GSB0000184749420000013
Figure RE-GSB0000184749420000014
式(II)中X为H或Br或I。
本发明以式(I)中的结构式为母核,创造性地进行改造母核,将中心原子O更换为S和Se,并在R1和R2位置预留官能团,得到其衍生物,具体结构见附图1,合成步骤见附图3。
本发明提供了所述光敏剂的制备方法,将式(I)中的母核分别与对羟基苯甲醛、3,5- 二溴-4-羟基苯甲醛和3,5-二碘-4-羟基苯甲醛进行Knoevenagel反应,得到一类新型光敏剂,具体结构见附图2,具体合成步骤见附图4。
作为优选,Knoevenagel反应的溶剂为乙腈,温度为85℃。
作为优选,Knoevenagel反应中的哌啶和乙酸的体积比为2∶1。
作为优选,引入卤(Br、I)原子,一方面可有效降低光敏剂酚羟基的pKa,使其更加适应生理pH值(Se代光敏剂为例,见附图5),另一方面促进光敏剂隙间穿越,提高光敏性。
作为优选,相同浓度下该类光敏剂与传统的光敏剂(MB)相比较,在可见光区有较大的吸收面积,见附图6。
作为优选,中心原子Q(O、S、Se)所对应的光敏剂,其波长依次红移(X为Br, O<S<Se;X为I,O<S<Se,见附图7),该类光敏剂具有较大的斯托克位移,有效避免了光敏剂的自吸收,减少能量损失。
此外,本发明还提供了一种光动力测试方法,将光敏剂很好地分散在PBS溶液中,测试方法如下:
1)DMA(60μM)、F127(0.3%)和光敏剂(2.5μM)溶于DMF,混合均匀,分散到PBS溶液中。
2)氙灯光源(490-700nm),5mW/cm2,每光照一分钟,使用紫外分光光度计依次扫描,扫描范围350-800nm,共计光照10min。
本发明实施例中引入硒元素的光敏剂,可以发挥重原子效应,有效促进隙间穿越,并且硒为人体重要的组成元素,因此,硒元素的引入可以降低光敏剂的生物毒性,并进一步提高光动力治疗的效果。
附图说明
图1所述光敏剂重要中间体的结构式。
图2所述光敏剂的结构式。
图3所述光敏剂主要中间体的合成路线。
图4所述光敏剂的合成路线。
图5以Se代光敏剂为例,在不同的pH条件下的紫外吸收。
图6相同浓度下部分光敏剂与传统光敏剂(MB)的紫外吸收。
图7所述光敏剂的紫外吸收。
图8所述光敏剂重要中间体及光敏剂结构通式。
具体实施方式
下面结合附图和具体实施例对本发明做出进一步的解释和说明,基于本发明中的实施例,本领域的技术人员,在没有做出创造性的劳动成果下所获得的其他实施例,都属于本发明的保护范围。
实施例一:合成EWGOalkyneEWGOazideEWGO,合成路线见附图3
1)邻羟基苯乙酮(10g,73.45mmol)溶于乙酸乙酯中,加入钠(7g,0.3mol),然后85℃搅拌4h。反应结束后,加入水(10mL),浓盐酸调节pH至3,乙酸乙酯萃取,无水硫酸钠干燥,旋蒸除去溶剂,得粗品化合物2。将粗品化合物2直接溶于乙醇(100mL),升温至80℃,逐滴滴加浓硫酸(4mL),继续反应5h。反应结束后,加入10%氢氧化钠水溶液调节pH至12,乙酸乙酯萃取,无水硫酸钠干燥,旋蒸除去溶剂,以石油醚和二氯甲烷作为洗脱剂进行柱层析提纯得纯品化合物3(4.3g,36.6%)。将化合物3(4.3g,26.8mmol)溶于乙酸酐(30mL),加入丙二腈(2.7g,40.87mmol),140℃搅拌过夜。反应结束后,旋蒸除去溶剂,以二氯甲烷作为洗脱剂进行柱层析得亮黄色固体EWGO(2.3g,41.2%)。
2)使用与EWGO相同的合成方法合成化合物7,化合物7(3.0g,8.1mmol)以乙酸乙酯(50mL)作为溶剂,加入钯炭(0.3g),使用氩气将反应瓶内的空气置换3次,插上氢气囊,反应12h。反应结束后,过滤,旋蒸除去溶剂,以石油醚和乙酸乙酯进行柱层析得到黄色固体化合物8(2.17g,95.6%)。化合物8(2.17g,7.74mmol)溶于乙腈(20mL),加入碳酸钾(2.14g,15.48mmol),升温至80℃,逐滴滴加炔丙溴(1.38g,11.6mmol),滴加完毕后,继续反应8h。反应结束后,过滤,旋蒸除去溶剂,以石油醚和二氯甲烷进行柱层析得黄色固体alkyneEWGO(2.2g,89.6%)。1H NMR(400MHz,CDCl3)δ(ppm)8.83(s,1H),6.95(s,1H),6.65(d,J=0.9Hz,1H),4.85(d,J=2.4Hz,2H),2.59(t,J=2.4Hz,1H),2.40(d,J=0.8Hz,3H),1.43(s,9H).13C NMR(100MHz,CDCl3)δ(ppm)161.37,160.92,153.37,153.20,138.68,124.10,117.26,116.16,110.93,105.28,100.91,76.92,76.81,59.75,56.09,36.00,29.67,20.34.
使用与alkyneEWGO相同合成方法得到azideEWGO1H NMR(400MHz,CDCl3)δ(ppm) 8.82(s,1H),6.82(s,1H),6.63(d,J=0.4Hz,1H),4.21(t,J=5.2Hz,2H),3.81(t,J=5.2 Hz,2H),2.40(d,J=0.4Hz,3H),1.45(s,9H).13C NMR(100MHz,CDCl3)δ(ppm)162.21,160.82,153.32,138.36,124.12,117.23,116.11,110.76,105.27,100.18,99.98,66.79,59.78,50.25,36.02,29.64,20.29.
实施例二:合成EWGSalkyneEWGS,合成路线见附图3
1)将磷酸(22.5g,229.6mmol)和五氧化二磷(40.7g,287.0mmol)在90℃搅拌一小时,对叔丁基苯硫酚(4.5mL,26.1mmol)和乙酰乙酸乙酯(3.3mL,26.1mmol)的混合物被逐滴滴加,继续反应2h。反应结束后,将反应液直接倒入冰水中,10%氢氧化钠水溶液调节pH至9,乙酸乙酯萃取,无水硫酸钠干燥,旋蒸除去溶剂,以石油醚和二氯甲烷为洗脱剂进行柱层析得到纯品黄色油状化合物10(3.09g,51.0%)。将化合物10(2g,8.6mmol)溶解在15mL乙酸酐中,加入丙二腈(0.68g,10.3mmol),140℃反应过夜,反应结束后,旋蒸除去溶剂,以石油醚和二氯甲烷为洗脱剂进行柱层析,得黄色固体EWGS(1.12g,46.4%)。1H NMR(400MHz,CDCl3)δ8.96(d,J=2.0Hz,1H),7.69(dd,J=8.8,2.0Hz,1H),7.58(d,J=8.4Hz,1H), 7.41(d,J=0.8Hz,1H),2.52(d,J=0.4Hz,3H),1.41(s,9H).13C NMR(100MHz,CDCl3) δ156.53,152.27,148.81,132.94,129.98,126.68,125.21,124.62,120.58,117.38,116.08, 67.36,35.70,31.09,23.51.
2)使用与化合物10相同的合成方法合成化合物12,化合物12(4.5g,21.8mmol)溶于二氯甲烷中,三溴化硼(6mL,63.5mmol)在0℃下被逐滴滴加,逐渐升至室温,搅拌过夜。反应结束后,加入冰水淬灭多余的三溴化硼,除去二氯甲烷,用乙酸乙酯萃取,无水硫酸钠干燥,旋蒸除去溶剂,以石油醚和二氯甲烷作为洗脱剂进行柱层析得白色固体化合物13(3.4g, 81.0%)。化合物13(4.4g,22.9mmol),碳酸钾(7.9g,57.2mmol)加入丙酮(50mL)中,升温至 80℃,逐滴滴加炔丙溴(2.7mL),反应8h。过滤,旋蒸除去丙酮,以石油醚和二氯甲烷为洗脱剂进行柱层析得白色固体化合物14(4.59g,87%)。化合物14(3.4g,14.78mmol)和丙二腈 (1.3g,19.7mmol)溶于乙酸酐(20mL),140℃搅拌过夜,旋蒸除去溶剂,以石油醚和二氯甲烷为洗脱剂进行柱层析得得alkyneEWGS(1.75g,42.5%)。1H NMR(400MHz,DMSO-d6)δ(ppm) 8.38(d,J=2.4Hz,1H),8.00(d,J=8.8Hz,1H),7.56(dd,J=8.8,2.4Hz,1H),7.38(s,1H), 4.93(d,J=2.0Hz,2H),3.69(t,J=2.Hz,1H),2.60(s,3H).13C NMR(100MHz,DMSO-d6) δ(ppm)157.21,155.58,151.89,129.65,129.00,125.64,121.86,119.83,117.91,116.53, 112.42,79.72,78.55,65.19,56.69,23.49.
实施例三:合成EWGSealkyneEWGSeazideEWGSe,合成路线见附图3
1)将邻溴苯甲酰氯(25g,0.114mol)溶于干燥的四氢呋喃(100mL)和三乙胺(100mL) 的混合溶液,除去反应液中的空气,加入二氯二(三苯基磷)钯(0.8g,11.4mmol)和碘化亚铜 (259.7mg,1.36mmol),氩气保护,冰水浴下逐滴滴加丙炔(0.114mol,1M的四氢呋喃溶液)。滴加完毕后,撤掉冰水浴,慢慢恢复至室温,继续反应17h。加入甲醇(10mL)淬灭反应,旋蒸除去溶剂,乙酸乙酯溶解粗品,5%硫酸水溶液、碳酸氢钠水溶液、饱和氯化钠水溶液分别洗涤2次,无水硫酸钠干燥,旋蒸除去溶剂,以石油醚和乙酸乙酯为洗脱剂进行柱层析,纯化得淡黄色油状化合物17(7.27g,28.6%)。硒粉(1.54g,19.5mmol)和硼氢化钠(0.54g, 14.27mmol)溶于DMF(60mL),100℃反应1h,氩气保护下缓慢滴加化合物18(2.03g,9.1mmol)的乙醇溶液,滴加完毕后,继续反应5h,反应结束后,旋蒸除去DMF,溶于乙酸乙酯,饱和食盐水洗涤3次,干燥,旋蒸除去溶剂,以石油醚和乙酸乙酯进行柱层析纯化得白色固体化合物18(1.32g,65.0%)。1H NMR(400MHz,CDCl3)δ(ppm)8.56(d,J=7.2Hz, 1H),7.63-7.54(d,J=6.8Hz,1H),7.53-7.41(m,2H),6.97(s,1H),2.51(s,3H).13C NMR (100MHz,CDCl3)δ(ppm)182.48,152.40,136.56,131.57,131.41,129.99,128.15,127.56, 127.03,25.04.
将化合物18(2.23g,10.4mmol)和丙二腈(0.79g,12mmol)溶于乙酸酐(15mL)中,140℃反应过夜。旋蒸除去溶剂,以石油醚和二氯甲烷为洗脱剂进行柱层析得黄色固体EWGSe(1.21g,42.9%)。1H NMR(400MHz,CDCl3)δ(ppm)8.73(d,J=4.8Hz,1H),7.71(d,J= 4.4Hz,1H),7.52(m,3H),2.60(s,3H).13C NMR(100MHz,CDCl3)δ(ppm)158.83,151.34,135.45,131.61,129.77,129.15,128.19,125.97,122.37,116.63,115.31,72.36,25.32.
2)使用与化合物18相同的方法合成化合物21,化合物21(2.5g,9.88mmol)以二氯甲烷(20mL)为溶剂,0℃下逐滴滴加三溴化硼(2.75mL,29.09mmol),逐渐升至室温,搅拌过夜,反应结束后,加入冰水淬灭多余的三溴化硼,用乙酸乙酯萃取,无水硫酸钠干燥,旋蒸除去溶剂,以乙酸乙酯和二氯甲烷为洗脱剂进行柱层析得白色固体化合物22(1.96g,83.0%)。化合物22(3.7g,15.47mmol),溶于乙腈(50mL),加入碳酸钾(4.27g,30.90mmol)升温至80℃,逐滴滴加炔丙溴(2.7g,22.7mmol),滴加完毕,继续反应8h。反应结束后,过滤,旋蒸除去溶剂,以石油醚和二氯甲烷进行柱层析得白色固体化合物23(3.3g,77.0%)。使用与化合物23 相同的合成方法得到白色固体化合物24。将化合物23(2g,7.2mmol)溶于20(mL)乙酸酐中,加入丙二腈(0.57g,8.6mmol),140℃搅拌过夜,反应结束后,旋蒸除去溶剂,以石油醚和二氯甲烷为洗脱剂进行柱层析,得黄色固体化合物alkynePSSe(0.99g,42.0%)。1H NMR(400MHz, DMSO-d6)δ(ppm)8.26(d,J=2.8Hz,1H),8.07(d,J=8.8Hz,1H),7.53-7.40(m,2H), 4.91(d,J=2.0Hz,2H),3.67(t,J=2.0Hz,1H),2.65(t,J=6.4Hz,3H).13C NMR(101MHz, DMSO-d6)δ(ppm)158.29,157.09,155.18,131.50,128.42,126.54,121.74,121.10,117.54, 116.14,114.42,79.62,78.70,69.90,56.70,25.39.
使用与alkynePSSe相同的合成方法合成黄色固体化合物azidePSSe1H NMR(400MHz,CDCl3)δ(ppm)8.21(d,J=2.8Hz,1H),8.04(d,J=8.8Hz,1H),7.47(d,J=0.8Hz,1H), 7.39(dd,J=8.8,2.8Hz,1H),4.28(t,J=4.8Hz,2H),3.75(t,J=5.2Hz,2H),2.65(s,3H). 13CNMR(100MHz,CDCl3)δ(ppm)158.45,157.77,155.08,131.51,128.23,126.57,121.71,121.57,117.69,116.16,113.32,69.89,67.82,49.80,25.35.
实例四:合成PSO-Br、PSO-IalkynePSO-I,合成路线见附图4
1)3,5-二溴-4-苯甲醛(0.8g,2.9mmol)溶于乙腈(20mL),分别加入哌啶(1.6mL)和乙酸(0.8mL),再加入适量的分子筛,搅拌,升温至85℃,加入EWGO(0.5g,2.4mmol),继续反应8h。反应结束后,过滤除掉分子筛,加入乙酸乙酯(50mL),1M的盐酸水溶液洗涤,过滤得粗品,以二氯甲烷为洗脱剂通过柱层析的方式进行纯化,得黄色固体化合物PSO-Br(0.42g,37.4%)。1H NMR(400MHz,DMSO-d6)δ(ppm)10.57(s,1H),8.73(d,J=8.4Hz,1H),8.02 (s,2H),7.94(m,1H),7.72(d,J=8.4Hz,1H),7.63(m,2H),7.49(d,J=15.6Hz,1H),6.98 (s,1H).
2)使用和PSO-Br相同的合成方法合成PSO-I1H NMR(400MHz,DMSO-d6)δ(ppm) 10.10(s,1H),8.72(d,J=8.4Hz,1H),8.18(s,2H),7.93(m,1H),7.72(d,J=8.4Hz,1H),7.64-7.56(m,2H),7.44(d,J=16.0Hz,1H),6.98(s,1H).13C NMR(101MHz,DMSO-d6) δ(ppm)158.60,157.95,153.30,152.44,139.40,136.18,135.90,131.37,126.60,125.12,119.39,119.03,117.68,117.57,116.32,107.04,87.85,60.44.HRMS(ESI):m/z[M+H]+calcd for C20H11I2N2O2 564.8905;found 564.8819.
3)使用和PSO-Br相同的合成方法合成alkynePSO-I1H NMR(400MHz,DMSO-d6)δ (ppm)10.05(s,1H),8.66(s,1H),8.16(s,2H),7.52(d,J=16.0Hz,1H),7.42(d,J=16.0 Hz,1H),7.33(s,1H),6.90(s,1H),5.10(d,J=2.Hz,2H),3.73(s,1H),1.40(s,9H).13C NMR(101MHz,DMSO-d6)δ(ppm)161.75,157.94,157.44,153.14,152.85,139.21,137.75, 135.10,131.67,123.25,119.41,118.09,116.64,110.69,106.86,102.22,87.59,79.70,78.44,58.28,56.92,55.37,36.00.
实例五:合成PSS-Br、PSS-I,合成路线见附图4
1)使用和PSO-Br相同的合成方法合成PSS-Br1H NMR(400MHz,DMSO-d6)δ(ppm)10.49(s,1H),8.80(s,1H),8.05(s,2H),7.91(m,2H),7.76(d,J=16.0Hz,1H),7.63(s,1H),7.34-7.25(d,J=16.8Hz,1H),1.36(d,J=2.2Hz,9H).13C NMR(101MHz,DMSO- d6)δ(ppm)156.23,152.45,151.80,148.31,134.37,132.23,131.95,131.09,130.24,128.14,126.27,124.63,124.56,121.78,118.11,116.43,112.66,66.76,35.80,31.11.
2)使用和PSO-Br相同的合成方法合成PSS-I1H NMR(400MHz,DMSO-d6)δ(ppm) 10.01(s,1H),8.80(d,J=1.2Hz,1H),8.22(s,2H),7.94-7.86(m,2H),7.71(d,J=16.4Hz, 1H),7.64(s,1H),7.27(d,J=16.0Hz,1H),1.36(s,9H).13C NMR(101MHz,DMSO-d6)δ (ppm)157.20,156.13,155.96,151.67,148.32,139.07,134.00,131.90,131.69,130.94,130.85,128.03,125.74,124.53,121.56,118.09,116.41,87.51,66.51,35.75,31.13.HRMS(ESI):m/z[M+H]+ calcd for C24H19I2N2OS 636.9302;found 636.9291.
实例五:合成PSSe、PSSe-Br、PSSe-IazidePSSe-I,合成路线见附图4
1)使用和PSO-Br相同的合成方法合成PSSe1H NMR(400MHz,DMSO-d6)δ(ppm) 10.06(s,1H),8.61(d,J=7.6Hz,1H),8.09(d,J=6.8Hz,1H),7.80-7.50(m,6H),7.31- 7.16(d,J=16.0Hz,1H),6.83(d,J=6.8Hz,2H).13C NMR(100MHz,DMSO-d6)δ(ppm) 160.07,159.07,151.84,139.03,134.12,132.58,130.56,130.47,129.58,128.59,126.85, 126.51,125.04,122.45,117.64,116.38,116.17,70.49.HRMS(ESI):m/z[M+H]+ calcd forC20H13N2OSe 377.0188;found 377.0181.
2)使用和PSO-Br相同的合成方法合成PSSe-Br1H NMR(400MHz,DMSO-d6,Figure S23)δ(ppm)10.48(s,1H),8.60(d,J=8.0Hz,1H),8.13-8.01(m,3H),7.83-7.61(m,4H), 7.19(d,J=16.0Hz,1H).13C NMR(100MHz,DMSO-d6,Figure S24)δ(ppm)159.04,152.37,150.70,135.53,134.10,132.69,132.26,130.60,130.52,129.68,128.70,128.31,126.39,123.83,117.43,115.92,112.72,71.80.HRMS(ESI):m/z[M]calcd for C20H10Br2N2OSe533.0810;found 533.0991.
3)使用和PSO-Br相同的合成方法合成PSSe-I1H NMR(400MHz,DMSO-d6)δ(ppm)10.01(s,1H),8.59(dd,J=8.0,1.2Hz,1H),8.22(s,2H),8.10(dd,J=7.6,1.2Hz,1H),7.81-7.59(m,4H),7.16(d,J=16.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ(ppm)159.10,157.16,150.95,139.13,135.37,134.12,132.66,132.08,130.59,129.68,128.68,127.88,126.42,123.65,117.47,115.95,87.65,71.65.HRMS(ESI):m/z[M+H]+ calcd forC20H11I2N2OSe 628.8121;found 628.8042.
4)使用和PSO-Br相同的合成方法合成azidePSSe-I1H NMR(400MHz,DMSO-d6)δ (ppm)9.69(s,1H),8.17(m,3H),8.01(d,J=8.8Hz,1H),7.68(m,2H),7.36(dd,J=8.4, 1.6Hz,1H),7.11(d,J=15.6Hz,1H),4.27(t,J=4.4Hz,2H),3.75(t,J=3.6Hz,2H).13C NMR(100MHz,DMSO-d6)δ(ppm)158.44,157.78,151.71,139.17,135.36,131.79,131.31,127.39,127.23,125.89,122.99,121.56,117.92,116.27,113.43,88.01,70.25,67.80,49.78.
以上所述仅是本发明的优选实施方式,应当指出,对于使用本技术领域的研究人员,在不脱离本发明技术原理的前提下,对这些实施例进行的多种修改,这些修改应该视为本发明的保护范围。

Claims (10)

1.一类光敏剂及中间体,其特征在于,具有如式(I)(II)所示的结构式:
Figure FSA0000184446170000011
其中,Q为O或S或Se,X为H或Br或I,R1为H或
Figure FSA0000184446170000012
R2为H或
Figure FSA0000184446170000013
2.根据权力要求1所述的中间体,其特征在于,创造性地进行改造母核,将中心原子O更换为S和Se,并在R1和R2位置预留官能团,得到其衍生物,合成路线如下:
Figure FSA0000184446170000014
3.根据权力要求1所述的光敏剂,其特征在于,将式(I)中的母核分别与对羟基苯甲醛、3,5-二溴-4-羟基苯甲醛和3,5-二碘-4-羟基苯甲醛进行Knoevenagel反应,得到一类新型光敏剂,合成路线如下:
Figure FSA0000184446170000031
Figure FSA0000184446170000041
4.根据权力要求3所述光敏剂的制备方法,其特征在于,Knoevenagel反应的溶剂为乙腈,温度为85℃。
5.根据权力要求3所述光敏剂的制备方法,其特征在于,Knoevenagel反应中的哌啶和乙酸的体积比为2∶1。
6.根据权力要求1所述光敏剂,其特征在于,引入卤(Br、I)原子,一方面可有效降低光敏剂酚羟基的pKa,使其更加适应生理pH值,另一方面促进隙间穿越,提高光敏性。
7.根据权力要求1所述光敏剂,其特征在于,相同浓度下该类光敏剂与传统的光敏剂(MB)相比较,在可见光区有较大的吸收面积。
8.根据权力要求1所述光敏剂,其特征在于,中心原子Q(O、S、Se)所对应的光敏剂,其波长依次红移(X为Br,O<S<Se;X为I,O<S<Se)。
9.根据权力要求1所述光敏剂,提供了一种光动力测试方法:1)DMA(60μM)、F127(0.3%)和光敏剂(2.5μM)溶于DMF,混合均匀,分散到PBS溶液中。2)氙灯光源(490-700nm),5mW/cm2,每光照一分钟,使用紫外分光光度计依次扫描,扫描范围350-800nm,共计光照10min。
10.根据权力要求2所述的中间体的制备方法,凡依照本策略做出的等同于替代或变换所制得的中间体,均在本发明的保护范围之内。
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