Current Chinese Science   Alexis Tigreros 1 and Jaime Portilla 1,* 1 Department of Chemistry, Faculty of Sciences, Universidad de Los Andes, Bogota D.C, Colombia Abstract: Among the huge number of fluorescent compounds described recently, pyrazole deriva- tives could play a paramount role in the design of probes for bioimaging applications–an important and simple tool for modern biology because of their easy synthetic methodologies, remarkable opti- cal properties and chelating points. In this mini-review, we highlighted some pyrazole derivatives that have shown remarkable performance in this area; from the detection of chromium (III) with limits of detection of 37 × 10 -12 M to sensing glutathione in biological samples, as well as small molecule labeling of drugs and identifying unhealthy cells such as HeLa and labeling subcellular organelles. Evidently, this important class of N-heterocyclic compounds is part of interesting appli- cations. A R T I C L E H I S T O R Y Received: June 11, 2020 Revised: October 31, 2020 Accepted: November 12, 2020 DOI: 10.2174/2210298101999201208211116 Keywords: Drugs labeling, fluorescent bioimages, fused heterocycles, Glutathione detection, metal ion and biomolecules sens- ing, pyrazole-complexes, pyrazole derivatives. 1. INTRODUCTION Fluorescent organic molecules are an important class of compounds in life sciences; they are widely used in biologi- cal imaging probes to detect ions and molecules and follow cellular processes. These compounds are commonly named chemosensors [1]. The development of useful fluorescent chemosensors is thus crucial for the advancement of modern biology, and recently has been a subject of intensive research [2]. In particular, practical biological imaging of specific ions, molecules, cellular and subcellular organelles is neces- sary to meet some requirements such as selective and sensi- tive probes by proper association and dissociation rate con- stants, high solubility in aqueous media and low excitation energy. Likewise, biological parameters also need to be ad- dressed: cell-membrane permeability, intracellular localiza- tion, low cytotoxicity, and the toxicity of the excitation wavelength used [3]. The design of an effective chemosensor is necessary to combine a binding site (receptor unit) with a signaling unit (active unit), usually attached through a spacer unit, Fig. (1). Upon addition of an analyte, its interaction with the probe induces a photophysical response that can be measurable via absorption and/or fluorescence [4]. Integration of pyrazole derivatives (PD) into molecular sensors arises as an important tool due to its well-known fluorescent properties [5-7] together with its versatile and efficient access synthetic [8, 9]. In addition, the presence of *Address correspondence to this author at the Department of chemistry, Faculty of Sciences, Universidad de Los Andes, Bogotá D.C., Colombia; Tel/Fax: +57 1 3394949. Ext. 2080; E-mail: jportill@uniandes.edu.co their adjacent chelating nitrogen atoms is highly valuable for metal-ion sensing [10]. Likewise, the relatively small size requires a molecular feature for biological applications due to the highest membrane permeability. Consequently, in this contribution, we present important PD (substituted pyrazole, pyrazoline and fused-pyrazole) applications for bioimages, ranging from the detection of heavy metal ions (Cr 3+ , Al 3+ , Ni 2+ and Cu 2+ ), molecules such as glutathione (GSH) to drugs-labeling and monitoring the photophysical changes on a probe due to the occurrence of highly apolar lipid droplets. The examples highlighted here are recent reports for the ap- plications of pyrazole-based probes in biological and life sciences. 2. ORGANOMETALLIC REACTION APPROACHES TO MONITORING METAL IONS The biochemistry study of transition metals is essential to understand their metallobiomolecule in terms of structure, function and mode of action. Between the transition metal cations, aluminum, chromium, copper, iron and nickel are of great interest due to their occurrence in food preparations, cosmetics, metabolic function mechanisms and health issues [11]. In analytical terms, there are efficient methods for these cations quantification with limits of detection (LODs) as low as 1.5 × 10 -12 M for Cr 3 +, [12] down to 1 × 10 -12 M for Fe 3+ [13] and 0.07mg kg -1 for Al 3 + [14]. However, those methods are known to be useless alternatives for biological applica- tions because they are sample destructive. Many of them require extraction [15,16] or pyrolysis/atomization [17] and cannot work in situ. Taking into account this inconvenient, small probes for absorption and emission quantification 2210-2914/21 $65.00+.00 © 2021 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.net Current Chinese Science, 2021, 1, 197-206 197 MINI-REVIEW ARTICLE Fluorescent Pyrazole Derivatives: An Attractive Scaffold for Biological Imaging Applications