基于硼酸/二醇识别的新型糖囊泡荧光传感器

摘要 合成了含有识别基团苯硼酸、喹啉发色团的新型双亲化合物,N-硼苄基-8-16烷基溴化喹啉（N-(boronobenzyl)-8-hexadecyloxyquinolinium bromide (BHQB)）.该化合物在可选择性溶剂中自组织成囊泡,囊泡的相变温度为52.4℃;研究了BHQB囊泡的荧光性质,结果表明：当向囊泡体系加入糖时,喹啉在425nm 峰逐渐增强而508nm峰急剧减弱,变化趋势为葡萄糖>果糖.实验结果表明,BHQB囊泡可以作为可植入、连续检测血糖浓度的荧光囊泡传感器,可望用于临床实际应用.     

新型含苯硼酸和萘双亲化合物的合成与囊泡荧光传感器的制备

合成了含有识别基团苯硼酸和荧光基团萘的新型对-[(5-十二烷氧基-1-氧基)萘]甲基苯硼酸{p-[(5-dodecyloxy-1-oxy) naphthalene] methyl-phenylboronic acid, DNMPBA}双亲化合物; 该化合物在THF/水选择性溶剂中自组织成囊泡, 囊泡的相变温度为56.8 ℃; 当向囊泡体系加糖时, DNMPBA囊泡中的萘生色基在345 nm的荧光峰强度急剧增强; 荧光强度随添加不同糖的变化趋势为果糖>葡萄糖>麦芽糖>乙二醇. 荧光强度增强可能归因于所形成的硼酸酯减弱了DNMPBA双亲化合物中一个氧原子孤对电子对萘生色基的猝灭作用而使荧光强度重新恢复. DNMPBA囊泡与糖的相互作用导致体系荧光强度变化, 使该体系有可能应用于检测生物物质如糖的化学传感器.     

检测维生素C的囊泡荧光传感器的制备

利用合成的含有识别基团苯硼酸和荧光读出基团萘的新型双亲化合物(DNMPBA)在THF/水选择性溶剂中自组织成囊泡,囊泡的相变温度为56.8℃;当向囊泡体系加维生素C时,DNMPBA囊泡中的萘生色基在345nm的荧光峰强度急剧减弱.荧光强度减弱归于所形成的硼酸酯增强了DNMPBA双亲化合物中一个氧原子孤对电子对萘生色基的淬灭作用.DNMPBA囊泡与维生素C的相互作用而导致体系荧光强度变化,使该体系有可能应用于检测生物物质如维生素C的化学传感器.     

选择性识别儿茶酚胺的长波长二硼酸荧光探针

儿茶酚胺是人体中重要的神经递质.选择性识别儿茶酚胺对帕金森氏综合症、嗜铬细胞瘤、神经母细胞瘤等疾病临床诊断及病理学研究具有重要意义.2-(4-二羟基硼烷)苯基喹啉-4-羧酸(PBAQA)与糖结合后荧光强度增强,与儿茶酚胺结合后荧光强度下降,可以作为选择性识别儿茶酚胺的荧光探针.但由于发射波长较短,PBAQA及其衍生物在荧光成像方面存在诸多限制.本文作者采用廉价易得的原料制备中间体PBAQA,然后经酰胺缩合、脱保护,制备氨基中间体,再与3-羧基硼酸缩合合成二硼酸.目标化合物的发射波长明显红移至500 nm左右,斯托克位移超过100 nm.初步活性测试发现,目标化合物与儿茶酚胺结合后荧光强度明显降低,且荧光强度改变与儿茶酚胺浓度存在线性关系,可作为选择性识别儿茶酚胺的长波长荧光探针.     

一个基于2-(4-二羟基硼烷)苯基喹啉-4-羧酸的长波长水溶性荧光探针

水溶性荧光探针2-(4-二羟基硼烷)苯基喹啉-4-羧酸(PBAQA)能实现儿茶酚的选择性识别,但发射波长较短.PBAQA及衍生物通常在285 nm进行荧光发射.本文报道以PBAQA为building block,通过化学合成制备一个新的二硼酸荧光探针.该化合物具有更长的发射波长,发射波长为364 nm.初步荧光活性测试结果表明,该化合物对多巴胺具有一定结合选择性.对寻找具有较长发射波长的硼酸荧光探针,实现探针分子在嗜铬细胞瘤等细胞组织进行荧光成像具有重要意义.     

合成双分子膜的研究 Ⅰ.单链1,5取代萘刚性生色基的双亲化合物的合成及其在稀溶液中的自组织规律

本文首次报道了系列单链、1,5取代萘刚性生色基团的两亲化合物C_nNaph(1,5)C_6N~+(n=16,12,10,8,6和4)的合成.用电镜、~1H NMR和DSC分别观察了该系列化合物在稀溶液中的聚集形态、聚集体内分子运动和物相变化.结果表明:当n≥8时,该系列双亲化合物在稀溶液中自组织成双层结构的囊泡,泡壁为双分子膜.n=6时,囊泡形状不完整.n=4时,聚集体无确定形态.     

选择性识别果糖的二硼酸荧光探针的合成及初步活性研究

通过以2-(4-二羟基硼烷)苯基喹啉-4-羧酸(PBAQA)和羧酸苯硼酸作为功能单体,哌嗪作为连接片,在甲醇溶液中经过进行两次酰胺缩合,得到具有双结合位点的新型水溶性二硼酸化合物.初步的荧光活性实验证明,果糖能够显著性地增强化合物11,12的荧光强度,结合常数显著高于其他糖类.加入75 mmol·L~(-1)果糖后,荧光强度增加12倍.因此,化合物11,12适合用作果糖选择性识别和检测的荧光探针.本文合成具有双结合位点的新型二硼酸化合物水溶性好,这对寻找新型水溶性硼酸荧光探针,提高探针分子在食品和医药中对果糖识别能力具有重要意义.     

全合成双分子膜分子激发态能量转移的研究

研究了全合成双分子膜内的分子激发态能量转移行为,给体为囊泡双亲分子上的联苯生色基,受体是通过静电相互作用结合在囊泡表面上的荧光黄阴离子.荧光黄猝灭联苯的荧光强度符合Sern-Volmer猝灭定律.探讨了囊泡在能量转移过程中的组织作用、转移效率与机制.通过研究由静电作用结合在囊泡表面上的荧光黄给体和四苯基卟啉受体间的能量转移,改善了光的输出,扩展了光波的覆盖范围.全合成双分子膜是能量转移的有效介质和良好的膜模拟剂.     

2-甲基-2,5'-(乙烯基)-二-8-羟基喹啉锌配合物的合成与荧光特性

设计合成了8-羟基喹啉衍生物3和4以及它们的金属锌配合物5和6,化合物3和4经质谱(MS)、元素分析(EA)、红外光谱(IR)、紫外光谱(UV)、核磁共振氢谱(1H NMR)进行表征,并测定了它们的荧光性质,与2-甲基-8-羟基喹啉(λmax=390 nm)比较表明,化合物3和4的荧光红移80～150 nm;用X射线单晶衍射仪测定了化合物3的晶体结构,晶体属于三斜晶系,空间群P-1,a=0.706 87(5)nm,b=0.962 03(6)nm,c=1.221 09(8)nm,α=86.735(4)°,β=87.840(4)°,γ=74.333(4)°,V=0.79801(9)nm3,Z=2,Dc=1.367Mg·m-3,μ=0.089 mm-1,F(000)=344,wR1=0.055 2,wR2=0.1581.化合物3的晶体结构确认了2-甲基-8-羟基喹啉甲酰化是在5位.测定了化合物5和6的荧光光谱及其荧光寿命,结果表明,化合物5和6发光的峰值为620nm和623nm,能够发出橙色的荧光,与2-甲基-8-羟基喹啉锌(λmax=515nm)比较,发生了明显的红移.化合物5和6的寿命分别为1.57ns和1.77ns,呈单指数衰减.     

新型单硼酸衍生物的合成及作为荧光探针对糖的选择性识别

合成了一种新的单硼酸衍生物,分别考察了其与D-葡萄糖、D-果糖、D-甘露糖的结合反应,通过硼酸衍生物荧光强度变化达到对糖的选择性识别.该化合物合成简单,作为糖的荧光探针,选择性好,生物基质中的氨基酸、蛋白质和生物胺均不干扰糖的测定.测定上述3种糖时,其浓度分别在0.01～1.0 μmol·L-1,0.1～2.0 μmol·L-1和0.2～3.0 μmol·L-1范围内,与荧光强度呈现良好的线性关系.方法具有较高的灵敏度,不同糖的检出限在0.008 2～0.10 μmol·L-1之间.应用于人血清中D-葡萄糖浓度的测定,结果满意.     

Wavelength-ratiometric near-physiological pH sensors based on 6-aminoquinolinium boronic acid probes

We describe the pH response of a set of isomeric water-soluble fluorescent probes based on both the 6-aminoquinolinium and boronic acid moieties. These probes show spectral shifts and intensity changes with pH, in a wavelength-ratiometric and colorimetric manner. Subsequently, changes in pH can readily be determined around the physiological level.Although boronic acid containing probes are known to exhibit pH sensitivity along with an ability for saccharide binding/chelating, the new probes reported here are considered to be unique and show an unperturbed pH response, even in the presence of high concentrations of background saccharide, such as with glucose and fructose, allowing for the predominant pH sensitivity. The response of the probes is based on the ability of the boronic acid group to interact with strong bases like OH⁻, changing from the neutral form of the boronic acid group, R-B(OH)₂, to the anionic ester, R-B⁻(OH)₃, form, which is an electron donating group. The presence of an electron deficient quaternary heterocyclic nitrogen center and a strong electron donating amino group in the 6-position of the quinolinium backbone, provides for the spectral changes observed upon OH⁻ complexation. In addition, by comparing the results obtained with systems separately incorporating 6-methoxy or 6-methyl substituents, the suppressed response towards monosaccharides, such as with glucose and fructose, can clearly be observed for these systems. Finally we compare our results to those of a control compound, BAQ, which does not contain the boronic acid group, allowing a rationale of the spectral changes to be made.     

Reduction-responsive vesicles composed of dimethylaminopropyl octadecanamide and dithiodipropionic acid

Reduction-responsive vesicle was prepared by salt-bridging N-[3-(dimethylamino)propyl]-octadecanamide (DMAPODA, a cationic amphiphile) using 3,3′-dithiodipropionic acid (DTPA, a disulfide diacid compound). According to the transmission electron micrograph and the fluorescence quenching degree (53.2%), it could be said that vesicles were formed when the DMAPODA to DTPA molar ratio was 2:2. The DMAPODA/DTPA associate was considered to be a building block for vesicle formation because DTPA could electrostatically associate with DMAPODA and help the cationic amphiphile assemble into the vesicle. On a differential scanning calorimetric thermogram, the DMAPODA/DTPA vesicle showed two endothermic peaks at 50.6°C and 63.2°C. The peak found at the lower temperature was possibly due to the solid gel-to-liquid crystal phase transition of the vesicular membrane and the peak found at the higher temperature was considered to be due to the melting of DMAPODA, indicating that unassociated DMAPODA coexisted with DMAPODA/DTPA vesicles. The release of calcein enveloped in the vesicle was promoted by DL-dithiothreitol, possibly because DTPA can be broken by the reducing agent to form mercaptopropionic acids and the vesicle could be disintegrated and/or the vesicular membrane would become defective.     

The effect of boronic acid acidity on performance of viologen-based boronic acids in a two-component optical glucose-sensing system

A two-component saccharide sensing system using the fluorescent dye, hydroxypyrene trisulfonic acid, combined with a boronic acid functional viologen as a receptor/quencher in pH 7.4 buffer solution has been further investigated. The effect of substituents on the acidity of the boronic acid was measured. The boronic acid pK_a changed in the expected manner when electron donating or withdrawing groups were present. The glucose binding constants were dependent on pK_a, but no simple correlation was observed for the Stern-Volmer quenching constants and the fluorescence signal modulation.     

硼酸类荧光受体识别单糖*

糖广泛存在于自然界中,与蛋白质和核酸一起并列构成生命体的三大物质单元。由于糖含有多个羟基,含硼酸基的有机物与二醇间有强烈结合作用,故硼酸基团常用于糖类识别和细胞标记。当荧光体与硼酸基团相连接时即可构建识别糖的荧光传感器。本文按发光团结构进行分类,分为：萘基硼酸类受体（包括对二甲氨基萘硼酸衍生物,N-取代的氨基萘硼酸衍生物,1,8-萘二甲酰亚胺为母体的单硼酸衍生物）、杂环硼酸类受体（包括含氮杂环硼酸衍生物、含硫杂环硼酸衍生物以及含氧杂环硼酸衍生物）、蒽环硼酸类受体、芘环硼酸类受体、紫精硼酸类受体及其它类型的硼酸类受体等,详细评述了自2002年以来含硼酸基团的新型荧光受体在单糖识别研究中的最新进展。     

One saccharide sensor based on the complex of the boronic acid and the monosaccharide using electrochemical impedance spectroscopy

A novel saccharide sensor based on the covalent interaction between the boronic acid and saccharides was developed. Poly (aminophenylboronic acid) (PABA) was prepared by electropolymerizing 3-aminophenylboronic acid on gold electrode surface in acidic solution. The boronic acid group of the PABA film can form covalent-bond with different saccharides, which can change the dielectric characteristics of the PABA film, and the change of the dielectric characteristic was saccharides concentration dependent. Four kinds of saccharides could be detected by using electrochemical impedance spectroscopy. Good linear relationship and high sensitivity were obtained by this method.     

A novel system of self-reproducing giant vesicles

Novel self-reproducing giant vesicles, consisting of a vesicular amphiphile with an imine group in its hydrophobic chain, were constructed. This vesicular amphiphile, the product of a dehydrocondensation reaction between amphiphilic aldehyde and a lipophilic aniline derivative, could be prepared within the giant vesicles. When a protected form of the aldehyde precursor was added to a suspension of giant vesicles containing the lipophilic aniline precursor and a catalyst, dehydrocondensation between the two precursors took place inside the vesicles and produced the same amphiphile as the one which constitutes the original vesicle. The newly formed amphiphiles self-assembled in the inner water pool to form small vesicles, which were eventually extruded through the outer layer of the original vesicle to the bulk water. Accordingly, this kinetic system can be designated as a self-reproducing system of giant vesicles.     

Multicolor saccharide-sensing chips based on boronic acid-containing thin films showing stepwise release and binding of dyes

A novel saccharide sensor that shows a distinct color change resembling a "traffic signal" was developed. By copolymerizing a boronic acid monomer and an amine monomer on a glass plate, a boronic acid-containing thin film was obtained. After adsorbing anionic blue and yellow dyes, the thin film was immersed in aqueous saccharide solutions containing a cationic red dye. As saccharide concentration increased, the thin film changed its color from green to red via yellow. Origin of the distinct color change was attributed to a stepwise release and binding of dyes.