Molecular Logic Gate Laboratory, Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea.
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 305-701, Republic of Korea.
Chem Asian J. 2019 Sep 16;14(18):3048-3084. doi: 10.1002/asia.201900672. Epub 2019 Sep 2.
In recent decades, HOCl research has attracted a lot of scientists from around the world. This chemical species is well known as an important player in the biological systems of eukaryotic organisms including humans. In the human body, HOCl is produced by the myeloperoxidase enzyme from superoxide in very low concentrations (20 to 400 μm); this species is secreted by neutrophils and monocytes to help fight pathogens. However, in the condition called "oxidative stress", HOCl has the capability to attack many important biomolecules such as amino acids, proteins, nucleotides, nucleic acids, carbohydrates, and lipids; these reactions could ultimately contribute to a number of diseases such as neurodegenerative diseases (AD, PD, and ALS), cardiovascular diseases, and diabetes. In this review, we discuss recent efforts by scientists to synthesize various fluorophores which are attached to receptors to detect HOCl such as: chalcogen-based oxidation, oxidation of 4-methoxyphenol, oxime/imine, lactone ring opening, and hydrazine. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively target HOCl and to study the level of HOCl selectivity through emission responses. Virtually all the reports here deal with well-defined and small synthetic molecular systems. A large number of published compounds have been reported over the past years; this growing field has given scientists new insights regarding the design of the chemosensors. Reversibility, for example is considered important from the stand point of chemosensor reuse within the biological system; facile regenerability using secondary analytes to obtain the initial probe is a very promising avenue. Another aspect which is also important is the energy of the emission wavelength of the sensor; near-infrared (NIR) emission is favorable to prevent autofluorescence and harmful irradiation of tissue; thus, extended applicability of such sensors can be made to the mouse model or animal model to help image internal organs. In this review, we describe several well-known types of receptors that are covalently attached to the fluorophore to detect HOCl. We also discuss the common fluorophores which are used by chemist to detect HOCl, Apart from the chemical aspects, we also discuss the capabilities of the compounds to detect HOCl in living cells as measured through confocal imaging. The growing insight from HOCl probing suggests that there is still much room for improvement regarding the available molecular designs, knowledge of interplay between analytes, biological applicability, biological targeting, and chemical switching, which can also serve to further sensor and theurapeutic agent development alike.
近几十年来,次氯酸(HOCl)的研究吸引了来自世界各地的许多科学家。这种化学物质作为真核生物(包括人类)生物系统中的重要参与者而广为人知。在人体内,HOCl 是由髓过氧化物酶酶从超氧化物中以非常低的浓度(20 至 400μm)产生的;这种物质由中性粒细胞和单核细胞分泌,以帮助抵抗病原体。然而,在所谓的“氧化应激”条件下,HOCl 有能力攻击许多重要的生物分子,如氨基酸、蛋白质、核苷酸、核酸、碳水化合物和脂质;这些反应最终可能导致许多疾病,如神经退行性疾病(AD、PD 和 ALS)、心血管疾病和糖尿病。在这篇综述中,我们讨论了科学家们最近努力合成各种荧光团,这些荧光团与受体结合以检测 HOCl,如:基于硫族元素的氧化、4-甲氧基苯酚的氧化、肟/亚胺、内酯开环和肼。这些合成分子,涉及合理的合成途径,使我们能够选择性地针对 HOCl,并通过发射响应研究其选择性水平。几乎所有在这里的报告都涉及定义明确和小的合成分子系统。在过去的几年中,已经报道了大量的已发表化合物;这个不断发展的领域为化学传感器的设计提供了新的见解。例如,从生物系统中化学传感器重复使用的角度来看,可逆性是很重要的;使用二次分析物来获得初始探针的简便可再生性是一个非常有前途的途径。另一个同样重要的方面是传感器发射波长的能量;近红外(NIR)发射有利于防止自发荧光和组织的有害辐射;因此,可以将这种传感器的广泛适用性扩展到小鼠模型或动物模型,以帮助对内脏器官进行成像。在这篇综述中,我们描述了几种共价连接到荧光团以检测 HOCl 的已知类型的受体。我们还讨论了化学家用于检测 HOCl 的常用荧光团。除了化学方面,我们还讨论了化合物在活细胞中检测 HOCl 的能力,这是通过共聚焦成像来衡量的。从 HOCl 探测中获得的不断深入的认识表明,在现有分子设计、分析物相互作用、生物适用性、生物靶向和化学转换方面,仍有很大的改进空间,这也可以为传感器和治疗剂的开发提供帮助。