Pyrazine-Based Chemosensors for Cation Detection

Abstract

Pyrazine (1,4-diazine) and its annulated derivatives are promising platforms for colorimetric and fluorescent chemosensors of biologically and environmentally relevant metal cations, including Hg2+, Cu2+, Zn2+, Pb2+, Fe3+, Al3+, Co2+, Ni2+, Ag+ and Cr3+. Their sensing potential arises from the strongly electron-deficient pyrazine ring, low-lying unoccupied molecular orbitals, and considerable synthetic versatility. This review systematically summarizes the structural diversity, metal-ion recognition strategies, photophysical response mechanisms, and practical applications of pyrazine-derived small-molecule chemosensors, with emphasis on studies published between 2015 and 2026. Reported architectures include pyrazinamide, pyrazinehydrazide, 2-acetylpyrazine, aminopyrazine, hydrazinopyrazine, aryl(hetaryl)pyrazine derivatives, pyrazines fused with five-membered carbo/heterocycles, quinoxalines, and pyrido [2,3-b]pyrazines. The analysis shows that N,N,O-tridentate chelation, CHEF/CHEQ, PET, ICT, ESIPT, FRET and AIE mechanisms govern the sensing behavior, providing detection limits from nanomolar to micromolar levels and enabling naked-eye, test-strip, and live-cell imaging applications. It is concluded that sensing performance is primarily determined by the chelating motif and the substitution pattern, while selectivity towards Cu2+ and Fe3+ remains the main limitation. Promising directions include AIE-active long-wavelength emitters, portable smartphone-assisted platforms, MOF-based architectures, and DFT-guided rational design of next-generation pyrazine chemosensors.