CN109942507A - 一种2,2-双氰基亚甲基噻唑及其应用 - Google Patents
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Abstract
本发明涉及一种2,2‑双氰基亚甲基噻唑，其化学结构如下式(I)所示。本发明所述的2,2‑双氰基亚甲基噻唑由2‑(4‑(4‑氰基苯基)噻唑‑2(5H)‑亚甲基)丙二腈和4‑(二苯基氨基)苯甲醛反应得到。本发明所述的2,2‑双氰基亚甲基噻唑具有近红外吸收，良好的光热转化效率，优异的光稳定和热稳定性，可以应用为光热剂。
Description
技术领域
本发明属于有机化学领域，涉及杂环化合物，具体涉及2,2-双氰基亚甲基噻唑衍生物。
背景技术
随着全球人口的快速增长和老龄化，癌症的发病率和死亡率正在迅速增长。然而，传统的临床肿瘤治疗方法，包括化学疗法，放射疗法和外科手术，表现出严重的副作用。光热疗法(PTT)作为肿瘤的非侵入性疗法之一，由于其毒性低、选择性高、耐药性小、副作用少，肿瘤破坏效率高等特点而备受关注。PTT在很大程度上取决于光热剂，其将吸收的近红外光转换成热量以消融肿瘤。
迄今为止，大多数可用于PTT的光热剂是无机材料，包括金属纳米材料(例如，Au、Pd和Ag纳米点)、碳纳米材料(例如，石墨烯和碳纳米管)、过渡金属二硫化物(例如，Ag2S、MoS2和WS2)。这些无机材料具有良好的稳定性和高的光热转换效率，但代谢性差，毒性高。公开号为107737349A的发明专利申请公开了一种硒化钼纳米杂合物用于PAI/PTT试剂，但是由于其中含有无机材料，可能存在代谢毒性。近红外吸收有机小分子(例如方酸菁染料、吲哚菁绿、卟啉、bodipy和二酮吡咯并吡咯-三苯胺)由于其快速代谢而具有优异的生物相容性而引起了人们的关注。
最近，Langa等人以三苯胺和2-羧甲基-2-氰基亚甲基噻唑为原料合成了两种化合物。这两种化合物显示出较强的红色荧光，但是其紫外吸收峰不在近红外区域，不能应用为光热试剂。(S.Gómez Esteban,P.de la Cruz,A.Aljarilla,L.M.Arellano and F.Langa,ORG LETT,19(2011)5362.)。中国专利(CN106008525)中设计合成了一种含三苯胺基的3，6-二(2-噻吩基)-2，5-二氢吡咯并[3，4-c]吡咯-1，4-二酮(DPP)衍生物作为肿瘤光热治疗试剂，但是其吸收峰在660nm处，属于红光区，光热转换效能较低。
发明内容
本发明要解决的技术问题是提供一种2,2-双氰基亚甲基噻唑，该化合物具有良好的光热转化效率，优异的光稳定和热稳定性。
本发明解决上述问题的技术方案是：
一种2,2-双氰基亚甲基噻唑，其结构式为下式(I)式所示：
本发明所述的2,2-双氰基亚甲基噻唑采用Knoevenagel缩合反应合成，可以由2-(4-(4-氰基苯基)噻唑-2(5H)-亚甲基)丙二腈与4-(二苯基氨基)苯甲醛反应得到。
本发明人推荐的方法由反应式(Ⅱ)表示：
本发明所述的2,2-双氰基亚甲基噻唑的最大吸收峰位于758nm处(属于近红外吸收)，具有良好的光热转化效率(高达38％)，而且光稳定性和热稳定性具佳，可用作为光热剂。
附图说明
图1为本发明所述的2,2-双氰基亚甲基噻唑的标准紫外-可见光光谱图。
图2为本发明所述的2,2-双氰基亚甲基噻唑的808nm激光照射前后的紫外-可见光光谱图。
图3为本发明所述的2,2-双氰基亚甲基噻唑的试管内升温曲线图。
图4为本发明所述的2,2-双氰基亚甲基噻唑的加热冷却循环曲线图。
具体实施方式
下面用具体实施例来进一步详细描述本发明的制备方法及其效果。
实施例1
2,2-双氰基亚甲基噻唑的制备：
2-(4-(4-氰基苯基)噻唑-2(5H)-亚甲基)丙二腈(1.25g，5.00mmol)和4-(二苯基氨基)苯甲醛(1.37g，5.00mmol)与乙酸铵的乙酸溶液在氮气保护下120℃下磁力搅拌48小时。然后将溶剂逐滴加入饱和碳酸氢钠溶液中。过滤后，滤渣使用二氯甲烷/甲醇(18：1)的混合物，通过柱色谱法纯化深色粗固体0.75g(产率34％)。
化合物的表征：
1H NMR(400MHz,MeOD),δ(ppm):7.58～7.59(d,4H),7.33～7.44(m,8H),7.19～7.23(t,2H),7.03～7.06(d,4H),6.68～6.70(d,1H).
13C NMR(100MHz,MeOD),δ(ppm):174.58,170.13,153.14,147.08,140.17,135.45,132.37,130.82,130.56,130.05,129.42,126.86,126.08,124.07,120.49,119.20,116.51,112.52,66.82.
IR(v-1,KBr):3452,2924,2859,2199,1648,1589,1493,1320,1182,1079,838,756,703.
上述检测结果证实制备的化合物为化学式(I)所示的2,2-双氰基亚甲基噻唑。
实施例2(2,2-双氰基亚甲基噻唑的紫外吸收)
配制浓度为1mM的2,2-双氰基亚甲基噻唑DMSO溶液，取10μL2,2-双氰基亚甲基噻唑DMSO溶液，加入10mL的离心管，用蒸馏水稀释到10mL得到浓度为10μM的2,2-双氰基亚甲基噻唑水溶液(含1％DMSO)。
采用Thermofisher Evolution 300紫外吸收光谱仪测量上述2,2-双氰基亚甲基噻唑水溶液的紫外吸收光谱，其结果如图1所示。2,2-双氰基亚甲基噻唑的紫外吸收光谱在758nm处显示一强吸收峰，属于近红外吸收。
实施例3(2,2-双氰基亚甲基噻唑的光稳定性)
配制浓度为1mM的2,2-双氰基亚甲基噻唑DMSO溶液，取10μL2,2-双氰基亚甲基噻唑DMSO溶液，加入10mL的离心管，用蒸馏水稀释到10mL得到浓度为10μM的2,2-双氰基亚甲基噻唑水溶液(含1％DMSO)。
采用808nm激光照射2,2-双氰基亚甲基噻唑水溶液10分钟后，采用ThermofisherEvolution 300紫外吸收光谱仪测量上述2,2-双氰基亚甲基噻唑水溶液的紫外吸收光谱，其结果如图2所示。从图2可以知道，808nm激光照射前后2,2-双氰基亚甲基噻唑紫外吸收光谱变化较小，说明2,2-双氰基亚甲基噻唑具有良好的光稳定性。
实施例4(2,2-双氰基亚甲基噻唑的光热转化效率检测)
按照文献(D.K.Roper,W.Ahn,M.Hoepfner,J.Phys.Chem.C,2007,111,3636.)所述方法检测得到2,2-双氰基亚甲基噻唑的光热转化效率为38％。
实施例5(2,2-双氰基亚甲基噻唑的光热转化性能)
按照实施例2所述方法配置浓度为10,20，40，80μM的2,2-双氰基亚甲基噻唑溶液，采用激光照射10min后(808nm，2.5W/cm2)用Fluke红外测温仪检测其温度。结果如图3所示。808nm激光照射后，溶液温度显著升高。例如浓度为40μM的2,2-双氰基亚甲基噻唑溶液808nm激光照射10min后，温度升高了28℃。结果表明2,2-双氰基亚甲基噻唑具有良好的光热转换能力。
实施例6(2,2-双氰基亚甲基噻唑的热稳定性)
采用加热冷却循环法检测2,2-双氰基亚甲基噻唑的热稳定性。首先用激光(808nm，2.5W/cm2)照射40μM的2,2-双氰基亚甲基噻唑溶液10min后，关闭激光，自然冷却10min后再开始激光照射，如此往复4个循环。其结果如图4所示。2,2-双氰基亚甲基噻唑溶液的升降温曲线在4个加热和冷却过程中变化很小。结果证实2,2-双氰基亚甲基噻唑溶液具有高热稳定性。
Claims (2)
1.一种2,2-双氰基亚甲基噻唑，其结构式为下式(I)式所示：
2.权利要求1所述的2,2-双氰基亚甲基噻唑在制备光热剂中的应用。
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| DE19502702A1 (de) * | 1995-01-28 | 1996-08-01 | Basf Ag | Thiazolmethinfarbstoffe |
| WO2007036561A2 (de) * | 2005-09-30 | 2007-04-05 | Siemens Aktiengesellschaft | Elektrochrome pasten mit neuen farbstoffen |
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| DE19502702A1 (de) * | 1995-01-28 | 1996-08-01 | Basf Ag | Thiazolmethinfarbstoffe |
| WO2007036561A2 (de) * | 2005-09-30 | 2007-04-05 | Siemens Aktiengesellschaft | Elektrochrome pasten mit neuen farbstoffen |
Non-Patent Citations (2)
| Title |
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| ANA ALJARILLA ET AL.,: "Push-pull triphenylamine based chromophores as photosensitizers and electron donors for molecular solar cells", 《TETRAHEDRON》 * |
| ZIKANG CHEN ET AL.,: "2-Dicyanomethylenethiazole based NIR absorbing organic nanoparticles for photothermal therapy and photoacoustic imaging", 《J. MATER. CHEM. B》 * |
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