Lights on 2,5-diaryl tetrazoles: applications and limits of a versatile photoclick reaction

Abstract

Recently, photoclick chemistry emerged as a powerful tool employed in several research fields, from medicinal chemistry and biology to material sciences. The growing interest in this type of chemical process is justified by the possibility to produce complex molecular systems using mild reaction conditions. However, the elevated spatio-temporal control offered by photoclick chemistry is highly intriguing, as it expands the range of applications. In this context, the light-triggered reaction of 2,5-diaryl tetrazoles with dipolarophiles emerged for its interesting features: excellent stability of the substrates, fast reaction kinetic, and the formation of a highly fluorescent product, fundamental for sensing applications. In the last years, 2,5-diaryl tetrazoles have been extensively employed, especially for bioorthogonal ligations, to label biomolecules and nucleic acids. In this review, we summarized recent applications of this interesting photoclick reaction, with a particular focus on biological fields. Moreover, we described the main limits that affect this system and current strategies proposed to overcome these issues. The general discussion here presented could prompt further optimization of the process and pave the way for the development of new original structures and innovative applications. Graphical abstract

Fluorescent Nanoassembly of Tetrazole-Based Dyes with Amphoteric Surfactants: Investigation of Cyanide Sensing and Antitubercular Activity

“…Studies. 1 H NMR titration studies of compound P1 (5 mM) were performed with tertbutyl salt of cyanide (1.0 equiv) in CDCl 3 . The spectra were recorded using identical parameters.…”

Fluorescence turn-on by photoligation – bright opportunities for soft matter materials

“…The photochemical ligation between 2,5-diaryl tetrazoles and alkenes is among the most prominent reactions that form fluorescent products, and substantial progress has been made in improving its photoreactivity, as well as exploiting its photoactivable fluorescent properties in different research areas. 30 The photochemical reactivity of the tetrazole towards dipolarophiles was initially reported by Huisgen and coworkers, observing the UV light-induced 1,3-dipolar cycloaddition reaction between 2,5-diphenyltetrazole and methyl crotonate. [31][32][33] An attractive feature of the tetrazoles is their accessibility -these compounds can be readily synthesised in a single reaction step via thermal coupling between inexpensive reagents, including benzensulphonyl hydrazones and arene diazonium salts.…”

Mechanistic Understanding and Reactivity Analyses for the Photochemistry of Disubstituted Tetrazoles

“…Although rather extensive studies have been performed, some practical issues need to be addressed. In most cases, tetrazoles and their derivatives can only be activated by UV-light. − Other interesting attempts were also conducted to extend excitation wavelengths to the visible-light region such as oligothiophene or pyrene-functionalized tetrazoles, which can definitely broaden the scope of applicability for the photochemistry of tetrazoles and be intended to avoid harmful ultraviolet radiation exposure. The question is how to establish rational guidelines for the design of substituent groups in regulating the absorption wavelengths of tetrazoles.…”