红光/近红外光硫醇荧光探针

小分子生物硫醇,包括半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH),在生理活动中扮演了重要的角色,其浓度的异常变化常与多种疾病息息相关,因此对其进行检测就显得尤为重要。近几年来,荧光探针因具有操作简便、时空分辨率高、损伤小和可视化等优势,在硫醇的识别领域成为了研究热点之一。而在已报道的众多的硫醇荧光探针中,红光或近红外光发射的荧光探针又因其具有背景干扰小、穿透深度深、拉曼散射影响小等特点,而受到研究者的青睐。本综述重点回顾了近三年来文献中报道的性能优异、发射红光或近红外光信号的硫醇荧光探针,根据构成探针分子荧光团的种类不同而进行分类介绍,包括罗丹明类、二吡咯氟硼类、花菁类、天然色素类、给受体型共轭化合物和聚集诱导发光型化合物六类。本文主要从分子设计、荧光性质、识别机理和成像应用等方面对各种荧光探针进行综述,同时展望了长波长发射的硫醇荧光探针的应用前景及待解决的问题。     

小分子生物硫醇荧光探针研究进展

半胱氨酸(Cys)、同型半胱氨酸(Hcy)和还原型谷胱甘肽(GSH)等小分子生物硫醇在人的生理活动中起着重要作用.近年来,生物和环境样品中小分子生物硫醇的检测引起科学家们极大的兴趣,生物硫醇荧光探针和比色传感器得到快速发展.根据探针与生物硫醇的反应机理,包括利用小分子生物硫醇中巯基与探针反应、巯基和氨基协同与探针反应,综述两年来生物硫醇小分子荧光探针的设计、合成与应用进展.     

检测活性硫物种小分子荧光探针的研究进展

总结了近两年来检测生物硫醇、H_2S以及SO_2衍生物荧光探针的研究现状,着重讨论了探针设计的传感机制、传感性能和生物应用方面的特征。检测生物硫醇方面,主要介绍了涉及多反应位点的多通道探针用于区分谷胱甘肽(GSH)、半胱氨酸(Cys)和同型半胱氨酸(Hcy);检测H_2S方面,重点介绍了基于叠氮基还原和亲核反应这两种机制设计的探针;检测SO_2衍生物方面,主要总结了根据迈克尔加成法和醛的加成机制设计的探针。这为构建新型荧光探针以研究活性硫物种的生理和病理作用奠定了基础。     

基于萘酰亚胺的生物硫醇探针的合成及对含硫醇氨基酸的检测

合成了以4-羟基萘酰亚胺为荧光团,2,4-二硝基苯磺酰氧基为特异性识别基团的生物硫醇探针4-(2,4-二硝基苯磺酰氧基)-正丁基-1,8-萘酰亚胺(DNSBN).吸收光谱和荧光光谱结果表明, DNSBN对半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)3种生物硫醇分子具有高效的检测识别能力,不受其它17种天然氨基酸的干扰.同时,通过荧光滴定实验证实了此探针是一种比率型探针,555 nm处的荧光强度与溶液中的生物硫醇分子浓度在0 ~ 20 μmol/L范围内呈良好的线性关系,对Cys、Hcy和GSH的检出限(3σ)分别为25.9、92.0和77.9 nmol/L.而吸收光谱、荧光光谱和质谱表征数据显示,生物硫醇与2,4-二硝基苯磺酸酯发生亲核取代反应并导致磺酸酯的分解.随着识别基团的解离,探针分子的d-PeT (donor-excited photoinduced electron transfer) 效应被解除,并出现非常明显的比色与荧光变化.HeLa细胞成像实验表明,探针DNSBN具有良好的生物相容性,能够对细胞外源性生物硫醇分子进行检测.     

基于分子内电荷转移机制半胱氨酸荧光探针的合成及应用

利用半胱氨酸(Cys)诱导的α,β-不饱和醛酮的加成环化反应来恢复探针的分子内电荷转移过程(ICT),成功合成一种专一性识别半胱氨酸的荧光探针。研究表明,探针分子仅对Cys具有显著的青色荧光增强响应,明显区分于非硫醇氨基酸和含硫醇氨基酸(同型半胱氨酸和谷胱甘肽),荧光可以恢复42倍,具有较好的稳定性。MDA-MB-231细胞内Cys的荧光成像证明了该有机分子具有潜在检测细胞内Cys的能力。     

一种基于查尔酮衍生物的荧光探针对巯基氨基酸的检测及细胞成像

生物硫醇(如半胱氨酸(Cys)、同型半胱氨酸(Hcy)及谷胱甘肽(GSH))与生物体和细胞中的许多生理和病理过程密切相关。荧光探针是对生物硫醇灵敏检测与成像的有力工具。本文合成了一种可检测生物硫醇的基于2′-羟基查尔酮荧光团开启型荧光探针1。探针中的2,4-二硝基苯磺酸酯基团既作为反应识别基团,又作为荧光猝灭基团。在DMSO/Tris(体积比8/2,pH=8.4)中,探针1与生物硫醇反应后释放出前体化合物3,3具有激发态分子内质子转移(ESIPT)和聚集诱导发光(AIE)特性,从而导致长波长荧光发射及较大的斯托克斯位移。探针1具有合成简单、灵敏度高、选择性高、细胞毒性低等优点,可以方便地检测溶液和活细胞中的生物硫醇。     

基于黄酮的长波长荧光探针用于检测体外和体内生物硫醇（英文）

半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)等生物硫醇在生理和病理过程中起着至关重要的作用,尤其是GSH在肿瘤细胞中过度表达,可以作为肿瘤的生物标志物.然而,同时区分活的正常细胞和肿瘤细胞存在着困难和挑战,因此设计并合成了一种基于N,N-二甲氨基萘黄酮(3)的肉眼可见“关-开”型长波长荧光探针(4).该探针对生物硫醇具有较高的选择性和较低的检测限,机理研究表明,生物硫醇催化探针的酯键断裂,生成了强荧光的黄酮3.该探针可用于活细胞和小鼠体内生物硫醇成像,并且对正常肝细胞HL-7702和肝癌细胞HepG2进行选择性成像.     

一种检测生物硫醇荧光探针的合成与应用

基于硫醇诱导的迈克尔加成反应阻断探针的光诱导电子转移过程(PET)合成了一种基于氟化硼络合二吡咯甲川(Bodipy)类染料的荧光探针,该探针具有高灵敏度和选择性,可在生理条件下检测硫醇。利用核磁和高分辨质谱对探针结构进行了表征。当向探针溶液加入硫醇(0~1 000μmol/L)时,可在探针溶液的绿色光谱区域引起一个显著的荧光增强响应(增强至150倍)。同时,探针可以检测相对较低浓度的硫醇,对于含有硫醇的氨基酸(半胱氨酸、谷胱甘肽和高半胱氨酸)的检出限分别为4.5×10~(-7),1.2×10~(-7),2.1×10~(-7)mol/L。此外,相对于其他氨基酸,探针对硫醇具有较高的选择性和灵敏度。该方法成功实现了细胞内硫醇的荧光成像,证明该荧光探针在生物体系中具有潜在的应用能力。     

选择性生物小分子硫醇荧光探针的研究进展

谷胱甘肽(GSH)、半胱氨酸(Cys)和高半胱氨酸(Hcy)作为生物体内含量较高的生物硫醇,在生物系统中起着重要作用。近年来,生物与环境样品中小分子生物硫醇的检测引起科学家们极大的兴趣,生物硫醇荧光探针和比色传感器得到快速发展。同时,作为更加精确的检测手段,选择性生物硫醇荧光探针的研究也得到了极大的关注。本文根据选择性生物硫醇荧光探针与生物硫醇的反应机理:醛基环化反应、丙烯酸酯加成环化反应、自然的化学连接反应、芳环取代重排反应和亲核加成-亲核取代反应,综述了近年来选择生物硫醇荧光探针的设计、合成与应用进展。     

基于蛋白模板金纳米簇及羟基氧化钴纳米片的激活型荧光纳米探针用于免标记和灵敏检测生物硫醇

该文基于牛血清白蛋白模板金纳米簇（BSA@AuNCs）与羟基氧化钴（CoOOH）纳米片构建了一种激活型荧光纳米探针用于生物硫醇的检测。带负电的BSA@AuNCs能通过静电吸附作用组装到带正电的CoOOH纳米片表面,与此同时,BSA@AuNCs的荧光由于内滤效应（IFE）有效地被CoOOH纳米片猝灭,形成BSA@AuNCs－CoOOH纳米探针。当向纳米探针溶液加入生物硫醇（0.05～150 μmol/L）时,生物硫醇与纳米探针中的CoOOH纳米片发生氧化还原反应,CoOOH纳米片被降解生成Co2+,同时释放出BSA@AuNCs,BSA@AuNCs荧光信号恢复。结果表明,该纳米探针可以检测低浓度的生物硫醇,对生物硫醇（半胱氨酸、谷胱甘肽和高半胱氨酸）的检出限为30 nmol/L。相对于其他的氨基酸、金属离子及糖类化合物,该纳米探针对生物硫醇具有较高的选择性并成功应用于人血清样品中生物硫醇的检测。     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.     

Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Both substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles have been synthesized by the 3+2 intramolecular dipolar cycloaddition of nitrilimines to alkynes. This cyclization has been extended to more versatile 3-bromo derivatives by the use of alkynylbromides as dipolarophiles.