CN115109227A - 一种新型多氟荧光聚合物及其制备方法 - Google Patents
一种新型多氟荧光聚合物及其制备方法 Download PDFInfo
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- CN115109227A CN115109227A CN202210971004.9A CN202210971004A CN115109227A CN 115109227 A CN115109227 A CN 115109227A CN 202210971004 A CN202210971004 A CN 202210971004A CN 115109227 A CN115109227 A CN 115109227A
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- Prior art keywords
- diol
- fluorescent polymer
- follows
- acetone
- polyfluoro
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Abstract
本发明涉及一种新型多氟荧光聚合物及其制备方法，以异氰酸酯和二醇的缩合反应为基础，引入含氟功能基团和荧光团，实现多氟荧光聚合物的制备。通过异氰酸酯与二醇的比例，以及亲水基团的引入调节脂水相容性，实现多氟二元醇水性聚合物荧光聚合物的制备。该新型多氟荧光聚合物因其含氟功能团的化学环境近乎一致，使得氟谱半峰宽窄，有效的提高了成像信号强度。此外，荧光团的引入，增加其成像的多样性，将使检测结果更加可靠。该探针在疾病诊断和治疗方面有着较好的应用前景。
Description
技术领域
本发明属于生物与新医药技术合成技术领域，尤其涉及了一种新型多氟荧光聚合物及其制备方法。
背景技术
利用活体成像技术对于疾病进行前期的检测，对疾病诊断和治疗具有重要意义，氟磁共振成像（19F MRI）由于其特异性，在生物成像和疾病诊断等领域受到越来越多的关注。氟成像的优点如下：第一，氟原子有着100%的丰度，自旋量子数为1/2，此外它与氢原子有着非常接近旋磁比（H：42.58 MHz·T–1，F：40.08 MHz·T–1），其敏感性是氢原子的83%（Drug Discov. Today, 2008, 13, 473）；第二，19F化合物的波谱特性变化范围非常广，而且人体中仅含微量的氟化物，存在于骨骼和牙齿中，它们对含氟造影剂成像的背景影响可以忽略不记（WIREs Nanomed. Nanobiotechnol.2010, 2, 431）。19F MRI的研究可追溯到1977年，由于化学和材料科学的限制，早期氟成像技术研究进展缓。直到最近几年，随着氟化学的快速发展，19F成像研究相关报道呈指数型出现。虽然一些先行者在该领域也做出了一些成绩（Chem. Rev., 2015, 115, 1106；Nano Research, 2016, 9(6): 1630），但是离市场的广泛应用还有一定差距。19F MRI示踪剂存在一些共性问题，如：成像剂成像灵敏度和清晰度的问题；成像剂稳定性和生物相容性的问题；成像剂代谢和对生物体的影响等。荧光成像作为一种常用的灵敏度高、成本低的成像手段，近年来，备受化学家们的青睐，开发出一系列新型荧光探针（Nanoscale, 2017, 9, 7163；Chin. J. Chem., 2018, 36, 25）。但是荧光成像空间分辨率低，组织渗透性差的缺点一直未被解决。
本发明设计一类新型的示踪剂-具有多氟结构的荧光聚合物，并对其多维成像进行初步探究。把荧光探针、氟核磁成像这两种检测手段有机结合起来，实现多维度呈现同一靶点的情况，将使检测结果更加可靠。
发明内容
为了解决上述现有技术中存在的问题，本发明提供了一种新型多氟荧光聚合物及其制备方法；这一新型荧光聚合物包含两类化学结构，多氟烷基醇封闭型聚氨酯型荧光聚合物和多氟二元醇水性聚合物荧光聚合物。
本发明的目的是这样实现的：
一种新型多氟烷基醇封闭型聚氨酯型荧光聚合物，其具有如下化学结构：
R1为异氰酸酯类化合物的母体结构，R1为：
R2为二醇类化合物，包括：己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400。
R3为全氟叔丁醇、(4-(1,2,2-三苯基乙烯基)苯基)甲醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮。
多氟烷基醇封闭型聚氨酯型荧光聚合物的制备方法，其特征在于，包括以下步骤：
1）将2当量的异氰酸酯类化合物溶解于有机溶剂A中，异氰酸酯化合物的溶度范围为：0.3 ～ 3 mmol/mL。
2）将1当量的二醇类化合物和0.001 ～ 0.01当量的催化剂DBTDL溶解于有机溶剂A中，二醇类化合物的溶度范围为：0.2 ～ 2 mmol/mL。混合均匀后，搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中，25 ～ 80℃反应3小时。
3）将2当量的全氟叔丁醇和荧光剂混合物加入反应体系中，全氟叔丁醇和荧光剂的摩尔比为1：0.5～1:0.05，继续搅拌1 ～ 3小时，旋除溶剂即可制得多氟烷基醇封闭型聚氨酯型荧光探针。
所述的反应溶剂A选自丙酮、四氢呋喃、乙腈、环己烷、乙酸乙酯、乙酸甲酯或1,4-二氧六环。优选丙酮或1,4-二氧六环。
本发明的第二个技术方案为多氟二元醇水性聚合物荧光聚合物，其具有如下化学结构：
R1为异氰酸酯类化合物的母体结构，R1为：
R4为二醇类化合物，包括：八氟-1,6-己二醇、1H,1H,10H,10H-全氟-1,10-癸二醇、六氟-1,5-戊二醇、十二氟-1,8-辛二醇、己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2,2-二羟甲基丙酸。
多氟二元醇水性聚合物荧光聚合物的制备方法，其特征在于，包括以下步骤：
1）将2当量的异氰酸酯类化合物溶解于丙酮中，异氰酸酯化合物的溶度范围为：0.3 ～ 3 mmol/mL。
2）将1当量的二醇类化合物的混合物A和0.001 ～ 0.01当量的催化剂DBTDL溶解于丙酮中，二醇类化合物的溶度范围为：0.2 ～ 2 mmol/mL。混合均匀后，搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中，25 ～ 80℃反应2小时。随后加入0.5当量二醇类化合物的混合物B，继续搅拌1小时；接着加入三乙胺搅拌30分钟，最后加入去离子水高速搅拌乳化，旋除溶剂丙酮，即可制得多氟二元醇水性聚合物荧光聚合物。
所述的二醇类化合物的混合物A为含氟二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮和普通二醇（如：己二醇、PEG-200等）三者的混合物。三者的投料摩尔比为：0.3 ～ 1: 0 ～ 0.2 ：0 ～ 0.7；
所述的二醇类化合物的混合物B为2,2-二羟甲基丙酸和短脂肪链二醇（如：己二醇、丁二醇等）的混合物，两者的投料摩尔比为：0.1 ～ 0.5: 0.5 ～ 0.9。
积极有益效果：（1）本发明将多氟化合物与荧光分子通过酰胺键选择性的结合起来，实现多维度呈现同一靶点的情况，将使检测结果更加可靠；（2）相比于多氟聚合物，多氟荧光聚合物可以同时获得荧光成像的图像和磁共振图像，通过比对研究为肿瘤临床诊断提供更加准确的影像支撑；（3）这一新型多氟荧光聚合物有着较多的亲水基团，生物相容性好。（4）该多氟荧光聚合物因其含氟功能团的化学环境近乎一致，使得氟谱半峰宽窄，有效的提高了成像信号强度。
附图说明
图1为实施例1中聚合物1的核磁氟谱图片；
图2是实施例3中聚合物3的红外光谱图；
图3是实施例3中聚合物3不同浓度下的荧光强度图谱；
图4是实施例8聚合物8不同浓度下的荧光强度图谱；
图5是聚合物8的19F 365 MHz核磁成像图谱。
具体实施方式
以下为本发明的详细实施步骤：
实施例1
将4.6克（0.02 mol）IPDI溶解于20毫升的丙酮中，将1.18克（0.01 mol）己二醇和0.08克DBTDL催化剂溶解于15毫升的丙酮中，搅拌下把己二醇的丙酮溶液滴加入IPDI溶液中，滴加完毕后室温下反应3小时，称取并加入3.5克（0.015 mol）全氟叔丁醇和1.8克(0.005 mol)(4-(1,2,2-三苯基乙烯基)苯基)甲醇，继续反应2小时，随后旋除溶剂，制得多氟荧光聚合物1。根据投料情况单一的低聚物两端封端剂R3有三种情况：1）都是全氟叔丁醇，2）一端是全氟叔丁醇，一端是四苯乙烯，3）两端都是四苯乙烯（如下式所示）。通过GPC测定，其峰值分子量为3854。红外特征数据如下：IR（cm-1）: 3363.03, 2928.26, 1685.31,1658.55, 1533.13, 1462.84，1402.58, 1170.21, 1037.26, 964.9, 788.81， 725.46。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.06 (s)。
实施例2
将4.6克（0.02 mol）IPDI溶解于20毫升的丙酮中，将1.18克（0.01 mol）己二醇和0.06克DBTDL催化剂溶解于15毫升的丙酮中，搅拌下把己二醇的丙酮溶液滴加入IPDI溶液中，滴加完毕后室温下反应3小时，称取并加入4.2克（0.018 mol）全氟叔丁醇和0.72克（0.002 mol）(4-(1,2,2-三苯基乙烯基)苯基)甲醇，继续反应2小时，随后旋除溶剂，制得多氟荧光聚合物2。通过GPC测定，其峰值分子量为3798。红外特征数据如下：IR（cm-1）:3363.33, 2928.24, 1685.35, 1658.45, 1533.23, 1462.74，1402.58, 1170.29,1037.38, 964.56, 787.1， 725.25。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.08(s)。
实施例3
将4.6克（0.02 mol）IPDI溶解于20毫升的1,4-二氧六环中，将5克（0.01 mol）二醇T5650E和0.04克DBTDL催化剂分散于15毫升的1,4-二氧六环中，搅拌下把T5650E的1,4-二氧六环溶液滴加入IPDI溶液中，滴加完毕后室温下反应3小时，称取并加入4.2克（0.018mol）全氟叔丁醇和0.66克（0.002 mol）3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮，继续反应2小时，随后旋除溶剂，制得多氟荧光聚合物3。根据投料情况单一的低聚物两端封端剂R3有三种情况：1）都是全氟叔丁醇，2）一端是全氟叔丁醇，一端是荧光素，3）两端都是荧光素。通过GPC测定，其峰值分子量为3620。红外特征数据如下：IR（cm-1）:3370.84, 2963.78, 2929.38, 1742.68， 1741.93, 1553.45, 1462.59，1261.53,965.93, 801.06, 724.82。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.69 (s)。
实施例4
将4.6克（0.02 mol）IPDI溶解于20毫升的四氢呋喃中，将2克（0.01 mol）二醇PEG-200和0.06克DBTDL催化剂分散于15毫升的四氢呋喃中，搅拌下把PEG-200的四氢呋喃溶液滴加入IPDI溶液中，滴加完毕后室温下反应3小时，称取并加入4.2克（0.018 mol）全氟叔丁醇和0.72克（0.002 mol）(4-(1,2,2-三苯基乙烯基)苯基)甲醇，继续反应3小时，随后旋除溶剂，制得多氟荧光聚合物4。通过GPC测定，其峰值分子量为3685。红外特征数据如下：IR（cm-1）: 3365.78, 2970.37, 2926.75, 1748.28， 1740.93, 1716.64，1541.12, 1244.08，1109.07， 933.54， 775.36， 646.15。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.48 (s)。
实施例5
将3.4克（0.02 mol）HDI溶解于25毫升的丙酮中，将5克（0.01 mol）二醇T5650E和0.05克DBTDL催化剂分散于20毫升的丙酮中，搅拌下把T5650E的丙酮溶液滴加入HDI溶液中，滴加完毕后室温下反应3小时，称取并加入4.2克（0.019 mol）全氟叔丁醇和0.33克（0.001 mol）3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮，继续反应2小时，随后旋除溶剂，制得多氟荧光聚合物5。通过GPC测定，其峰值分子量为3255。红外特征数据如下：IR（cm-1）: 3367.93, 2958.43, 2936.12, 1746.39， 1740.08, 1558.72, 1459.37，1239.28, 985.79, 808.32, 736.18。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.57 (s)。
实施例6
将5.25克（0.02 mol）HMDI溶解于25毫升的丙酮中，将0.9克（0.01 mol）丁二醇和0.046克DBTDL催化剂分散于10毫升的丙酮中，搅拌下把丁二醇的丙酮溶液滴加入HMDI溶液中，滴加完毕后室温下反应3小时，称取并加入4.2克（0.019 mol）全氟叔丁醇和0.36克（0.001 mol）(4-(1,2,2-三苯基乙烯基)苯基)甲醇，继续反应2.5小时，随后旋除溶剂，制得多氟荧光聚合物6。通过GPC测定，其峰值分子量为3429。红外特征数据如下：IR（cm-1）:3737.26， 3614.85, 2922.41, 1696.41， 1675.83, 1544.75, 1054.29，888.13, 795.49,676.02。核磁氟谱数据为：19F NMR (376 MHz, CDCl3)δ -74.55 (s)。
实施例7
将4.6克（0.02 mol）IPDI溶解于15毫升的丙酮中，将1.3克（0.005 mol）八氟-1,6-己二醇、0.33克（0.001 mol）荧光素、0.8克（0.004 mol）PEG-200和0.04克DBTDL催化剂分散于15毫升的丙酮中，搅拌下把二醇的混合液滴加入IPDI溶液中，滴加完毕后加热至50度反应2小时，随后加入0.67克（0.005 mol）2,2-二羟甲基丙酸和0.45克（0.005 mol）丁二醇，继续搅拌1小时；接着加入0.1克三乙胺搅拌30分钟，旋除一半溶剂后，加入20毫升的去离子水高速搅拌乳化30分钟，旋除剩余溶剂丙酮，即可制得多氟二元醇水性荧光聚合物7。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定，其峰值分子量为2785。绝干聚合物的红外特征数据如下：IR（cm-1）: 3321.71, 2903.01, 1756.39， 1739.28, 1564.16, 1461.52，1357.93，1303.56, 1172.48，1100.56，1043.45，965.93, 843.25, 726，725.33。核磁氟谱数据为：19FNMR (376 MHz, DMSO-d6)δ -69.61 (s).
实施例8
将4.6克（0.02 mol）IPDI溶解于15毫升的丙酮中，将2.1克（0.008 mol）八氟-1,6-己二醇、0.33克（0.001 mol）荧光素、0.2克（0.001 mol）PEG-200和0.06克DBTDL催化剂分散于15毫升的丙酮中，搅拌下把二醇的混合液滴加入IPDI溶液中，滴加完毕后加热至60度反应2小时，随后加入0.26克（0.002 mol）2,2-二羟甲基丙酸和0.72克（0.008 mol）丁二醇，继续搅拌1小时；接着加入0.1克三乙胺搅拌30分钟，旋除一半溶剂后，加入20毫升的去离子水高速搅拌乳化30分钟，旋除剩余溶剂丙酮，即可制得多氟二元醇水性荧光聚合物8。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定，其峰值分子量为2958。绝干聚合物的红外特征数据相比于实施例7变化不大，具体如下：IR（cm-1）: 3321.75, 2903.35, 1756.56， 1739.75,1564.76, 1463.15，1353.68，1301.22, 1164.59，1104.36，1033.69，965.91, 842.14,725.59，722.34。核磁氟谱数据为：19F NMR (376 MHz, DMSO-d6)δ -69.43 (s).
实施例9
将3.4克（0.02 mol）HDI溶解于15毫升的丙酮中，将2.1克（0.006 mol）十二氟-1,8-辛二醇、0.33克（0.001 mol）荧光素、1.5克（0.003 mol）T5650E和0.06克DBTDL催化剂分散于15毫升的丙酮中，搅拌下把二醇的混合液滴加入IPDI溶液中，滴加完毕后加热至50度反应2小时，随后加入0.26克（0.002 mol）2,2-二羟甲基丙酸和0.72克（0.008 mol）丁二醇，继续搅拌1小时；接着加入0.1克三乙胺搅拌30分钟，旋除一半溶剂后，加入20毫升的去离子水高速搅拌乳化30分钟，旋除剩余溶剂丙酮，即可制得多氟二元醇水性荧光聚合物9。其中R4为十二氟-1,8-辛二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定，其峰值分子量为2796。绝干聚合物的红外特征数据如下：IR（cm-1）: 3330.02, 2961.12, 1719.61， 1635.43, 1657.91, 1557.91，1460.41，1304.80, 1164.59，1086.59，876.74, 770.57, 725.53，649.12。核磁氟谱数据为：19F NMR (376 MHz, DMSO-d6)δ -68.79 (s).
实施例10
将3.4克（0.02 mol）HDI溶解于15毫升的丙酮中，将2.1克（0.008mol）八氟-1,6-己二醇、0.33克（0.001 mol）荧光素、0.5克（0.001mol）T5650E和0.08克DBTDL催化剂分散于15毫升的丙酮中，搅拌下把二醇的混合液滴加入IPDI溶液中，滴加完毕后加热至50度反应2小时，随后加入0.13克（0.001 mol）2,2-二羟甲基丙酸和0.56克（0.009 mol）乙二醇，继续搅拌1小时；接着加入0.1克三乙胺搅拌30分钟，旋除一半溶剂后，加入20毫升的去离子水高速搅拌乳化30分钟，旋除剩余溶剂丙酮，即可制得多氟二元醇水性荧光聚合物10。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、T5650E或乙二醇。通过GPC测定，其峰值分子量为2689。绝干聚合物的红外特征数据如下：IR（cm-1）: 3330.02, 2961.12, 1719.61， 1635.43, 1657.91, 1557.91，1460.41，1304.80,1164.59，1086.59，876.74, 770.57, 725.53，649.12。核磁氟谱数据为：19F NMR (376 MHz,DMSO-d6)δ -68.79 (s).
实施例11
将3.4克（0.02 mol）HMDI溶解于15毫升的丙酮中，将2.1克（0.008 mol）八氟-1,6-己二醇、0.33克（0.001 mol）荧光素、0.5克（0.001 mol）T5650E和0.06克DBTDL催化剂分散于15毫升的丙酮中，搅拌下把二醇的混合液滴加入HMDI溶液中，滴加完毕后加热至50度反应2小时，随后加入0.13克（0.001 mol）2,2-二羟甲基丙酸和1.05克（0.009 mol）己二醇，继续搅拌1小时；接着加入0.1克三乙胺搅拌30分钟，旋除一半溶剂后，加入20毫升的去离子水高速搅拌乳化30分钟，旋除剩余溶剂丙酮，即可制得多氟二元醇水性荧光聚合物8。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、T5650E或己二醇。通过GPC测定，其峰值分子量为2958。绝干聚合物的红外特征数据如下：IR（cm-1）: 3733.23， 3623.51, 2935.28, 1768.41，1725.67， 1675.35, 1544.23,1048.34，875.55, 795.49, 647.02。核磁氟谱数据为：19F NMR (376 MHz, DMSO-d6)δ -68.59 (s).
荧光强度实验和核磁共振谱实验
称取多氟荧光聚合物3配置质量浓度为20 mg/mL, 10 mg/mL, 5 mg/mL, 1 mg/mL, 0.5 mg/mL, 0.2 mg/mL, 0.1 mg/mL的DMSO溶液各20毫升，测量其荧光强度，测量结果（图3），该探针的荧光强度与聚合物的浓度呈正相关。
称取多氟二元醇水性荧光聚合物8配置质量浓度为50 mg/mL, 10 mg/mL, 5 mg/mL, 2 mg/mL, 1 mg/mL, 0.5 mg/mL, 0.2 mg/mL的DMSO溶液各20毫升，测量其荧光强度，测量结果（图4），该探针的荧光强度与聚合物的浓度呈正相关。
进一步称取多氟二元醇水性荧光聚合物8，用氘代二甲基亚砜配置成浓度为：100mg/mL, 20 mg/mL, 5 mg/mL和1 mg/mL不同浓度的溶液，对其进行体外19F MRI成像效果测试，结果显示（图5），该探针的19F SNR与探针的浓度呈正相关。
本发明的技术方案所公开的技术手段不仅限于上述实施方式所公开的技术手段，还包括由以上技术特征任意组合所组成的技术方案。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也视为本发明的保护范围。
Claims (7)
1.一种新型多氟荧光聚合物，其特征在于，具有如下化学结构：
其中，R1为异氰酸酯类化合物的母体结构，R1为：
R2为二醇类化合物，包括：己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400；
R3为全氟叔丁醇、(4-(1,2,2-三苯基乙烯基)苯基)甲醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮。
2.如权利要求1所述的新型多氟荧光聚合物的制备方法，其特征在于，包括以下步骤：
将2当量的异氰酸酯类化合物溶解于有机溶剂A中，异氰酸酯化合物的溶度范围为：0.3～ 3 mmol/mL；
将1当量的二醇类化合物和0.001 ～ 0.01当量的催化剂DBTDL溶解于有机溶剂A中，二醇类化合物的溶度范围为：0.2 ～ 2 mmol/mL；混合均匀后，搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中，25 ～ 80℃反应3小时；
将2当量的全氟叔丁醇和荧光剂混合物加入步骤（2）的反应体系中，全氟叔丁醇和荧光剂的摩尔比为1：0.5～1:0.05，继续搅拌1 ～ 3小时，旋除溶剂即可制得多氟烷基醇封闭型聚氨酯型荧光聚合物。
3.根据权利要求2所述的一种新型多氟荧光聚合物的制备方法，其特征在于，所述步骤的反应溶剂A选自丙酮、四氢呋喃、乙腈、环己烷、乙酸乙酯、乙酸甲酯或1,4-二氧六环；优选丙酮或1,4-二氧六环。
4.一种新型多氟荧光聚合物，其特征在于，具有如下化学结构：
R1为异氰酸酯类化合物的母体结构，R1为：
R4为二醇类化合物，包括：八氟-1,6-己二醇、1H,1H,10H,10H-全氟-1,10-癸二醇、六氟-1,5-戊二醇、十二氟-1,8-辛二醇、己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2,2-二羟甲基丙酸。
5.如权利要求4所述的一种新型多氟荧光聚合物的制备方法，其特征在于，包括以下步骤：
将2当量的异氰酸酯类化合物溶解于丙酮中，异氰酸酯化合物的溶度范围为：0.3 ～ 3mmol/mL；
将1当量的二醇类化合物的混合物A和0.001 ～ 0.01当量的催化剂DBTDL溶解于丙酮中，二醇类化合物的溶度范围为：0.2 ～ 2 mmol/mL；混合均匀后，搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中，25 ～ 80℃反应2小时；随后加入0.5当量二醇类化合物的混合物B，继续搅拌1小时；接着加入三乙胺搅拌30分钟，最后加入去离子水高速搅拌乳化，旋除溶剂丙酮，即可制得多氟二元醇水性聚合物荧光聚合物。
6.根据权利要求5所述的一种新型多氟荧光聚合物的制备方法，其特征在于，所述步骤的二醇类化合物的混合物A为含氟二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮和普通二醇三者的混合物；三者的投料摩尔比为：0.3 ～ 1: 0 ～ 0.2 ：0 ～ 0.7。
7.根据权利要求5所述的一种新型多氟荧光聚合物的制备方法，其特征在于，所述步骤的所述的二醇类化合物的混合物B为2,2-二羟甲基丙酸和短脂肪链二醇的混合物，两者的投料摩尔比为：0.1 ～ 0.5: 0.5 ～ 0.9。
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