荧光素类荧光分子探针

荧光素衍生物是重要的荧光探针,在检测和生物成像等领域中显示出巨大的前景。因此,急需对功能性荧光素结构探针的设计策略进行深入研究。通常通过引入醛基或酯化到荧光素呫吨环和苯部分来构建探针,由于其高活性,这些衍生物可以与分析物复合以发生颜色和荧光强度的变化。本文总结了荧光素的修饰位点及方法,介绍了荧光素探针的合成、性质及应用,并对近五年荧光素探针对不同分析物(包括金属阳离子、阴离子、小分子和生物大分子)的检测进行分类说明,旨在为高灵敏度荧光素探针的筛选和生物检测提供参考,并推动其在分析物传感和检测中的进一步应用。     

Coherent third-order spectroscopic probes of molecular chirality

The third-order optical response of a system of coupled localized anharmonic vibrations is studied using a Green's function solution of the nonlinear exciton equations for bosonized excitons, which are treated as interacting quasiparticles. The explicit calculation of two-exciton states is avoided and the scattering of quasiparticles provides the mechanism of optical nonlinearities. To first-order in the optical wave vector we find several rotationally invariant tensor components for isotropic ensembles which are induced by chirality. The nonlocal nonlinear susceptibility tensor is calculated for infinitely large periodic structures in momentum space, where the problem size reduces to the exciton interaction radius. Applications are made to alpha and 3(10) helical infinite peptides.     

萘酰亚胺类荧光分子探针的研究进展

荧光分子探针作为一种有效的金属离子检测手段,不仅使用方便,而且具有高灵敏度,高选择性等突出的优点.作者综述了萘酰亚胺类荧光分子探针的最新研究进展;指出萘酰亚胺化合物具有独特的荧光化学性质(如荧光量子产率高、荧光发射波长适中、斯托克斯位移大、光稳定性好、结构易于修饰等),因此被广泛应用于荧光探针研究领域,并且在合成、离子识别、检测及细胞成像等方面不断取得新的应用.     

Synthesis and evaluation of polyhydroxylated near-infrared carbocyanine molecular probes

[reaction: see text] A new near-infrared (NIR) fluorescent molecular probe derived from indocarbocyanine dye and galactose was prepared, and the procedure was optimized. The presence of a nonionic polyhydroxyl moiety between hydrophobic groups enhances solubility and possibly minimizes aggregation in aqueous solutions. The structural framework of this molecule provides multivalent sites for labeling diverse molecules.     

Quadruplex-based molecular beacons as tunable DNA probes

Molecular beacons (MBs) are fluorescent nucleic acid probes with a hairpin-shaped structure in which the 5' and 3' ends are self-complementary. Due to a change in their emissive properties upon recognition with complementary sequences, MBs allow the diagnosis of single-stranded DNA or RNA with high mismatch discrimination, in vitro and in vivo. Whereas the stems of MB hairpins usually rely on the formation of a Watson-Crick duplex, we demonstrate in this report that the preceding structure can be replaced by a G-quadruplex motif (G4). Intramolecular quadruplexes may still be formed with a central loop composed of 12 to 21 bases, therefore extending the sequence repertoire of quadruplex formation. G4-MB can efficiently be used for oligonucleotide discrimination: in the presence of a complementary sequence, the central loop hybridizes and forms a duplex that causes opening of the quadruplex stem. The corresponding G4-MB unfolding can be detected by a change in its fluorescence emission. We discuss the thermodynamic and kinetic opportunities that are provided by using G4-MB instead of traditional MB. In particular, the intrinsic feature of the quadruplex motif facilitates the design of functional molecular beacons by independently varying the concentration of monovalent or divalent cations in the medium.     

Fluorescent molecular rotors as probes for polymers

The use of a molecular rotor (1,1-dicyano-4-(4'-dimethylaminophenyl)-1,3-butadiene) as a fluorescent probe was proved to be of great interest for the study of polymers. First, the rotor can detect the critical time of the glass effect in the bulk polymerization of MMA into PMMA due to viscosity change, this will allow a better control of the process and is complementary to the information issued from the use of the fluorescent pyrene probe which is sensitive to the gel effect. Second, the cinnamylidene rotor was able to detect the formation of hydrophobic microdomains for cationic amphiphilic polymers in their aggregation modes when they were solubilized in water, both polarity and viscosity changes are playing a role. The possibility of incorporation of various molecular fluorescent rotors in polymers beads was also studied.     

Synthesis of novel molecular probes inspired by harringtonolide

A novel harringtonolide-inspired scaffold containing a cycloheptatriene ring and two fused cyclopentane rings has been synthesised from simple starting materials. The scaffold, containing a similar substitution pattern and relative stereochemistry to the complex diterpenoid, has been enumerated into a small library of derivatives. One of these library members has been converted into a sub-library of substituted triazoles using copper-catalysed azide-alkyne cycloaddition (click) chemistry. The scaffold may be useful in drug discovery or in the preparation of additional molecular probes for chemical biology.     

A thermodynamic investigation into the binding properties of DNA functionalized gold nanoparticle probes and molecular fluorophore probes

We report the first quantitative analysis of the oligonucleotide binding thermodynamics for DNA functionalized gold nanoparticle probes and compare our findings to molecular fluorophore probes on a sequence-for-sequence basis. With proper design, nanoparticle probes show significantly increased binding over molecular fluorophore probes under identical conditions. This is significant because probe binding strength directly influences detection sensitivity limits.     

Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for realtime, in-situ...     

Nitrile and thiocyanate IR probes: molecular dynamics simulation studies

Nitrile- and thiocyanate-derivatized amino acids have been found to be useful IR probes for investigating their local electrostatic environments in proteins. To shed light on the CN stretch frequency shift and spectral lineshape change induced by interactions with hydrogen-bonding solvent molecules, we carried out both classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations for MeCN and MeSCN in water. These QM/MM and conventional force field MD simulation results were found to be inconsistent with the experimental results as well as with the high-level ab initio calculation results of MeCN-water and MeSCN-water potential energies. Thus, a new set of atomic partial charges of MeCN and MeSCN is obtained. By using the MD simulation trajectories and the electrostatic potential model recently developed, the CN and SCN stretching mode frequency trajectories were obtained and used to simulate the IR spectra. The C[Triple Bond]N frequency blueshifts of MeCN and MeSCN in water are estimated to be 9.0 and 1.9 cm(-1), respectively, in comparison with those of gas phase values. These values are found to be in reasonable agreement with the experimentally measured IR spectra of MeCN, MeSCN, beta-cyano-L-alanine, and cyanylated cysteine in water and other polar solvents.     

Oxygen imaging of living cells and tissues using luminescent molecular probes

Oxygen imaging of biological cells and tissues is becoming increasingly important in cell biology and in the pathophysiology of various hypoxia-related diseases. The optical oxygen-sensing method using luminescent probes provides very useful, high spatial resolution information regarding oxygen distribution in living cells and tissues. This review focuses on recent advances in biological oxygen measurements based on the phosphorescence quenching of probe molecules by oxygen, and on hypoxia-sensitive fluorescent probes. Special attention is devoted to metal complex probes, Pt(II)- and Pd(II)-porphyrins, Ru(II) complexes, and Ir(III) complexes. Current knowledge regarding the mechanism of phosphorescence quenching of metal complexes by oxygen is described in relation to the oxygen sensitivity of the probes, and recent advances in optical oxygen probes and detection techniques for intracellular and tissue oxygen measurements are reviewed, emphasizing the usefulness of chemical modifications for improving probe properties. Tissue oxygen imaging and hypoxic tumor imaging using these metal complex probes demonstrate the vast potential of optical oxygen-sensing methods using luminescent probes.     

Near-infrared fluorescent molecular probes for imaging and diagnosis of nephro-urological diseases

Near-infrared (NIR) fluorescence imaging has improved imaging depth relative to conventional fluorescence imaging in the visible region, demonstrating great potential in both fundamental biomedical research and clinical practice. To improve the detection specificity, NIR fluorescence imaging probes have been under extensive development. This review summarizes the particular application of optical imaging probes with the NIR-I window (700–900 nm) or the NIR-II window (1000–1700 nm) emission for diagnosis of nephron-urological diseases. These molecular probes have enabled contrast-enhanced imaging of anatomical structures and physiological function as well as molecular imaging and early diagnosis of acute kidney injury, iatrogenic ureteral injury and bladder cancer. The design strategies of molecular probes are specifically elaborated along with representative imaging applications. The potential challenges and perspectives in this field are also discussed.

Near-infrared fluorescent molecular probes with improved imaging depth and optimized biodistribution have been reviewed, showing great potential for diagnosis of nephro-urological diseases.     

Characterisation of zeolitic catalysts by the adsorption of molecular probes

Few examples of the characterisation by FTIR spectroscopy supplemented by the use of CO₂, CO and NO molecular probes of acid, base and redox centres in zeolites (NaX and NaY) and zeolitetype (HSAPO-34, a silicon-aluminophosphate, and CoAPO-18, a cobalt-aluminophosphate) catalysts, are illustrated.     

Recent developments in molecular dynamics simulations of fluorescent membrane probes

Due to their sensitivity and versatility, the use of fluorescence techniques in membrane biophysics is widespread. Because membrane lipids are non-fluorescent, extrinsic membrane probes are widely used. However, the behaviour of these probes when inserted in the bilayer is often poorly understood, and it can be hard to distinguish between legitimate membrane properties and perturbation resulting from probe incorporation. Atomistic molecular dynamics simulations present a convenient way to address these issues and have been increasingly used in recent years in this context. This article reviews the application of molecular dynamics to the study of fluorescent membrane probes, focusing on recent work with complex design fluorophores and ordered bilayer systems.     

基于光化学探针的分子键盘锁研究进展

分子键盘锁作为一类新型的分子逻辑器件,其信号输出依赖于特定顺序的信号输入组合,可以在分子水平上保护信息。光化学探针分子以其选择性好、灵敏度高、易于实现在线分析以及可通过目视比色识别和原位检测等特点成为目前研究的热点。本文介绍了基于光化学分子探针发展起来的分子键盘锁,根据信号输入类型主要有阳离子输入、阴离子输入和阳离子/阴离子混合输入等类型。最后,展望了分子键盘锁的发展趋势。     

Bifunctional atomic force microscopy probes for molecular screening applications

Force mapping with the atomic force microscope (AFM) allows the simultaneous acquisition of topography and probe-sample interaction data. For example, AFM probes functionalised with an antigen can be employed to map the spatial distribution of recognition events on a substrate functionalised with its specific antibody. However, to date this method has been limited to the detection of single receptor-ligand species. Were the detection of multiple receptor-ligand interactions possible, force mapping would offer great scope as a sensitive tool for bioassay and screening applications. We have developed an immobilisation strategy, which allows two different molecular species (in this case human serum albumin and the β subunit of human chorionic gonadotropin) to be present simultaneously on an AFM probe. Single point force spectroscopy results have revealed the ability of such probes to discriminate between their corresponding recognition points (anti-HSA and anti-βhCG IgG antibodies). As a control, force measurements were re-recorded in the presence of the known antigen (free in solution) for each antibody species and a marked decrease in the frequency of specific interaction is observed. As an additional control interactions between anti-βhCG IgG and the multifunctional probe are taken in the presence of free βhCG (“true” antigen) and free HSA (“false” antigen). It is shown that measurements recorded in the presence of a non-related protein species results in no change in either the force observed or the frequency of specific interactions, further confirmation that the specificity of force observed is due to the separation of antibody-antigen complex.