核酸光化学生物学

光敏感基团作为光化学开关被广泛应用于各种生物过程的光调控中。特别是过去十几年内,核苷酸、寡聚核苷酸和DNA/RNA的光敏修饰策略得到了长足的发展,并在细胞信号传导和靶基因的功能调控等诸多生物学研究中发挥重要的作用。本文主要针对常用的光敏感基团、光敏感核酸及其化学生物学研究进展进行简要综述,并对未来核酸光化学生物学的研究进行了展望。     

双光子激光共焦扫描显微技术在环境化学中的应用及展望

介绍了双光子激光共焦扫描显微技术的基本原理,评述了该技术与传统荧光显微技术和单光子激光共焦扫描显微技术的异同,并且结合双光子激光共焦扫描显微技术在实际工作中的应用,评述了其在环境化学中的应用潜力及发展前景.     

双光子诱导产生单重态氧的三重态光敏剂的研究

自2001年以来,双光子敏化产生单重态氧的三重态光敏剂的研究取得了一定的进展。双光子三重态光敏剂对肿瘤组织的近红外激光和红外激光的光动力治疗作用具有广阔的应用前景。本文重点分析了近些年已报道的双光子三重态光敏剂种类,如疏水性、水溶性等不同的敏化剂;介绍了可以根据分子的激发态性质、利用化学手段对双光子三重态敏化剂的性质以及光敏产生单重态氧的量子产率进行调控;概括了双光子三重态敏化剂的相对和绝对双光子横截面的测量方法;总结了双光子三重态敏化剂发展中面临的一些关键问题,并展望了双光子三重态敏化剂的发展方向。     

双光子光聚合技术及其研究进展

本文对双光子光聚合技术进行了比较全面系统的综述,主要介绍了双光子光聚合的基本原理,国内外双光子光聚合光敏引发体系和具有大的双光子吸收截面有机分子的研究现状以及双光子光聚合技术的潜在应用领域.     

末端基团对芴类衍生物分子非线性光学性质的影响

通过采用预估矫正的时域有限差分方法数值求解速率方程-光场强度方程,研究了纳秒激光脉冲在具有不同末端基团的对称性芴类衍生物分子2,7-双(4′-(二甲基氨基)苯乙烯基)-9-氢-芴(F1分子)和2,7-双(4′-硝基苯乙烯基)-9-氢-芴(F2分子)中的动力学传播过程以及光限幅效应,分析了两种分子的光限幅特性随传播距离(z)、粒子数密度(N)以及脉冲宽度(τ)的变化情况,并且拟合了两种分子的动态双光子吸收(TPA)截面。计算结果表明,该系列分子具有较大的双光子吸收截面以及较好的光限幅效应。此外,F2分子的末端基团―NO2与F1分子的末端基团―N(CH3)2相比具有更强的得电子能力,因而使得F2分子具有更大的跃迁偶极矩,双光子吸收截面增大,光限幅效应更为明显。     

香豆素肟酯类双光子引发剂的合成及性能研究

开发高效的双光子引发剂是提升双光子聚合速度的关键。本文基于光致脱羧机制,设计并合成了两种以共轭香豆素作为生色团、肟酯作为引发基团的双光子引发剂,并通过实验测试结合模拟计算对该类引发剂的光物理和光化学行为进行了研究。结果表明,该类引发剂在400~500 nm区域具有较强吸收,在LED可见光辐照下发生分解,具有光漂白特性,光解后释放的活性种可引发丙烯酸酯类单体聚合。利用双光子三维微纳成型技术,该类香豆素肟酯化合物可有效用于构建高分辨率的三维微纳结构。并通过量子化学计算,对该类引发剂的引发机理进行了探讨。     

双光子技术在光生酸剂中的应用研究

自2000年以来,双光子技术开始应用于光生酸剂体系中,并取得了一定的研究进展。双光子技术在光生酸剂中的应用主要有两种情况:一是单分子体系,即光生酸剂分子本身具有较高的双光子吸收截面,可以在双光子激发下产生光酸;二是双分子体系,由具有较高吸收截面的敏化剂分子和光生酸剂分子组成,通过分子间电子转移的方式产生光酸。本文就这一类具有特殊光学性质的有机分子体系的构成及其应用进行了综述,介绍了不同类型的可以利用双光子技术的光生酸剂体系,总结了双光子技术在光生酸剂发展中面临的一些关键问题,展望了双光子技术在光生酸剂中的发展方向。     

生命及其分子机器

一、生命和生命科学生物学进入分子水平是一件完成于50年代前后,即从1945到1965年间二十年中的大事。它的发生也是顺理成章和水到渠成的。当生物学已经发展到了若无关于蛋白和核酸这两类生物大分子三维结构的确切知识几乎无法前进的时候,正好X射线晶体学和结构化学已经成长到足以来担当这项带有突破性质的任务了。当时生物学在其自身的发展中已逐渐明确:蛋白作为一类分子,既可为生物体充当构架材料,也可为生命执行各种特殊使命;DNA(去氧核糖核酸)则充当生命之蓝图,即为决定生物总体设计的分子。     

噻吩基卟啉衍生物的单光子和双光子吸收性质的理论研究

本文理论上研究了两个系列的噻吩基卟啉衍生物,这种衍生物在可见光区具有大的双光子吸收截面。用密度泛函理论和ZINDO-SOS方法,计算了分子的几何构型、电子结构,单光子和双光子吸收性质。结果显示噻吩单元的数目影响分子的单光子和双光子吸收性质。具有两个或三个噻吩基团的噻吩基卟啉衍生物在较大范围内具有可用于实际应用中的双光子吸收响应,这一性质有利于这类分子在光限幅中的应用。插入乙炔基有利于扩大共轭范围,增加分子的双光子吸收截面。同时,乙炔基团的加入导致了单光子和双光子波长的红移。从高透明性和相对大的非线性光学响应考虑,噻吩基卟啉衍生物是一类有应用前景的双光子吸收材料。     

迈克尔反应受体分子化学生物学研究

迈克尔受体是烯键或炔键与吸电子基团共轭相连形成的官能团,含有这样官能团的化学小分子能与亲核试剂发生迈克尔加成反应,因此称为迈克尔反应受体分子。迈克尔反应受体分子是一类重要的生理活性分子,它们直接或间接参与许多生命过程,同时也是细胞中许多信号转导途径的调节者,在化学生物学研究中起着重要的作用。本文对迈克尔反应受体分子化学生物学研究进展进行了综述。     

Dendrimer Conjugation Enables Multiphoton Chemical Neurophysiology Studies with an Extended π‐Electron Caging Chromophore

We have developed a caged neurotransmitter using an extended π‐electron chromophore for efficient multiphoton uncaging on living neurons. Widely studied in a chemical context, such chromophores are inherently bioincompatible due to their highly lipophilic character. Attachment of two polycarboxylate dendrimers, a method we call “cloaking”, to a bisstyrylthiophene (or BIST) core effectively transformed the chromophore into a water‐soluble optical probe, whilst maintaining the high two‐photon absorption of over 500 GM. Importantly, the cloaked caged compound was biologically inert at the high concentrations required for multiphoton chemical physiology. Thus, in contrast to non‐cloaked BIST compounds, the BIST‐caged neurotransmitter can be safely delivered onto neurons in acutely isolated brain slices, thereby enabling high‐resolution two‐photon uncaging without any side effects. We expect that our cloaking method will enable the development of new classes of cell‐compatible photolabile probes using a wide variety of extended π‐electron caging chromophores.     

"Turn-on" fluorescent sensing with "reactive" probes

Chemical probes are valuable tools for the investigation of biochemical processes, diagnosis of disease markers, detection of hazardous compounds, and other purposes. Therefore, the development of chemical probes continues to grow through various approaches with different disciplines and design strategies. Fluorescent probes have received much attention because they are sensitive and easy-to-operate, in general. To realize desired selectivity toward a given analyte, the recognition site of a fluorescent probe is designed in such a way to maximize the binding interactions, usually through weak molecular forces such as hydrogen bonding, toward the analyte over other competing ones. In addition to such a supramolecular approach, the development of fluorescent probes that sense analytes through chemical reactions has witnessed its usefulness for achieving high selectivity, in many cases, superior to that obtainable by the supramolecular approach. Creative incorporations of the reactive groups to latent fluorophores have provided novel chemical probes for various analytes. In this feature article, we overview the recent progress in the development of turn-on fluorescent probes that are operating through chemical reactions triggered by target analytes. Various chemical reactions have been implemented in the development of many reactive probes with very high selectivity and sensitivity toward target analytes. A major emphasis has been focused on the type of chemical reactions utilized, with the hope that further explorations can be made with new chemical reactions to develop reactive probes useful for various applications.     

Photocontrollable analyte-responsive fluorescent probes: a photocaged copper-responsive fluorescence turn-on probe

Analyte-responsive fluorescent probes are valuable chemical tools for dissecting complex living systems. However, the major shortcoming of fluorescent probes is that once they enter the cells, control over them is basically lost. It is critical to regulate fluorescent probes in a spatial and temporal manner, as functions of biomolecules are spatiotemporal. On the other hand, light can be manipulated in time and in the application site, so the photocaging technique allows researchers to control the biomolecules of interest in a temporal and spatial fashion. Herein, we propose for the first time the combination of the merits of sensing and photocaging technologies, which may afford the caging version of analyte-responsive fluorescent probes, referred to as photocontrollable analyte-responsive fluorescent probes (PCAFPs). These "smart" fluorescent probes apparently have the intrinsic advantage of spatiotemporal control when compared to traditional fluorescent probes, as the "sensing activity" of PCAFPs is photocontrollable. This should enable biologists to interrogate complex biological systems in a spatial and temporal manner with an innovative chemical tool. In this work, for proof of concept, we report the rational design, synthesis, photocontrollable sensing in solution and in living cells, and mechanistic studies of a molecular prototype of PCAFP for copper as the first paradigm of this new class of smart fluorescent probes. We believe that PCAFPs represent a substantial breakthrough in the sensing and photocaging fields, and that the general concept of PCAFPs should be broadly applicable for a wide variety of biologically relevant species.     

Two‐Photon Fluorescent Probes for Metal Ions

Two‐photon microscopy (TPM) has become an indispensible tool in biology and medicine owing to the capability of imaging the intact tissue for a long period of time. To make it a versatile tool in biology, a variety of two‐photon probes for specific applications are needed. In this context, many research groups are developing two‐photon probes for various applications. In this Focus Review, we summarize recent results on model studies and selected examples of two‐photon probes that can detect intracellular free metal ions in live cells and tissues to provide a guideline for the design of useful two‐photon probes for various in vivo imaging applications.     

From One‐Photon to Two‐Photon Probes: “Caged” Compounds,Actuators, and Photoswitches

Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two‐photon excitation has significant advantages deep in biological tissues, but raises problems in the design of “smart” probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two‐photon probes.     

Fluorescent molecular probes for the detection of chemical warfare agents and their mimics

Owing to their direct toxic effects on human beings, animals, and plants, chemical warfare agents (CWAs) and their mimics have become widespread in chemical warfare and agriculture. The considerable concerns about their entry into biological systems and the residues in environment stimulate the development of rapid and sensitive methods for the detection and analysis of this family of compounds. In the progress of sensitive, selective, and fast responsive detection, fluorescent molecular probes have been widely used in the detection of CWAs in recent years. Here the recent reports on the design of fluorescent molecular probes and their advantages in the detection of CWAs were reviewed. Furthermore, the extensive interests accelerate the development of novel fluorescent molecular probes and detection techniques in this field.     

Computational design of improved two‐photon active caging compounds based on nitrodibenzofuran

Nitrodibenzofuran (NDBF) has recently been established as photolabile protecting group and efficiently used as two‐photon active cage. In this work, a computational approach is exploited to rationally design improved two‐photon active caging groups based on this NDBF chromophore. For this objective, first the two‐photon absorption (TPA) properties of NDBF are investigated in detail and a suitable theoretical approach for the reliable simulation of TPA spectra of this class of compounds is identified. Then, virtual chemical modifications are performed by introduction of substituents at the chromophore and replacement of the central furan ring by pyrolle, thiophene, and borrole heterocycles. Subsequently, the TPA properties of the resulting compounds are computed, and the influences of the chemical modifications on TPA properties investigated in detail. The most promising candidates with largely increased two‐photon uncaging efficiencies are dimethylamino‐substituted derivatives of NDBF, nitrodibenzopyrrol, and nitrodibenzothiophene. © 2012 Wiley Periodicals, Inc.     

Expanded utility of the native chemical ligation reaction

The post-genomic era heralds a multitude of challenges for chemists and biologists alike, with the study of protein functions at the heart of much research. The elucidation of protein structure, localization, stability, post-translational modifications, and protein interactions will steadily unveil the role of each protein and its associated biological function in the cell. The push to develop new technologies has necessitated the integration of various disciplines in science. Consequently, the role of chemistry has never been so profound in the study of biological processes. By combining the strengths of recombinant DNA technology, protein splicing, organic chemistry, and the chemoselective chemistry of native chemical ligation, various strategies have been successfully developed and applied to chemoselectively label proteins, both in vitro and in live cells, with biotin, fluorescent, and other small molecule probes. The site-specific incorporation of molecular entities with unique chemical functionalities in proteins has many potential applications in chemical and biological studies of proteins. In this article, we highlight recent progress of these strategies in several areas related to proteomics and chemical biology, namely, in vitro and in vivo protein biotinylation, protein microarray technologies for large-scale protein analysis, and live-cell bioimaging.     

Artificial light-harvesting antennae: electronic energy transfer by way of molecular funnels

Electronic energy transfer (EET) plays a critical role in many biological processes and is used by nature to direct energy to a site where chemical reactions need to be initiated. Such EET can occur over large distances and can involve many individual molecules of identical, similar or disparate chemical identity. Advances in spectroscopy and data processing have allowed the rates of EET to be measured on extremely fast timescales such that improved mechanistic insight becomes feasible. At the same time, highly sophisticated synthetic operations have been devised that facilitate the isolation and purification of elaborate multi-component molecular arrays. A key feature of these arrays concerns the logical positioning of individual units in a way that favours directed EET along the molecular axis or along some other preferred pathway. The availability of these novel molecular materials allows close examination of popular theoretical models and paves the way for the development of advanced molecular sensors, artificial light harvesters, fluorescent labels and sensitizers. Of particular interest is the spectacular growth in the application of boron dipyrromethene dyes as basic reagents in such artificial photon collectors and these compounds have dominated the market in recent years because of their synthetic versatility and valuable photophysical properties. In this article, recent developments in the field are highlighted in terms of synthesis and subsequent spectroscopic exploration.