Barkha Rathee, Garima Rathee, Parul Bhalla
The selective optical detection of neutral organic and biologically relevant analytes remains a central challenge in analytical chemistry, as the absence of formal charge and structural diversity among targets render conventional ion-responsive sensing frameworks largely inadequate. Schiff base-derived chemosensors, defined by their synthetically accessible azomethine (-C[double bond, length as m-dash]N-) core, have emerged as particularly well-suited molecular scaffolds for addressing this gap, owing to their modular structural tunability, straightforward synthesis from commercially available precursors, and capacity to support diverse photophysical transduction mechanisms. While early investigations centred predominantly on transition and heavy metal ion detection, research over the past decade has decisively expanded the scope of Schiff base probes toward neutral analytes of biological, environmental, and security relevance. This review critically evaluates peer-reviewed studies (2000-2025) reporting Schiff base-derived colorimetric and fluorescent probes for the detection of amino acids, biothiols, reactive selenium species, vitamins, hydrazine, thiophenols, pesticides, herbicides, nitroaromatic explosives, formaldehyde, volatile organic compounds, and selected inorganic neutral molecules. Sensing mechanisms, including photoinduced electron transfer (PET), intramolecular charge transfer (ICT), chelation-enhanced fluorescence (CHEF), excited-state intramolecular proton transfer (ESIPT), Förster resonance energy transfer (FRET), and aggregation-induced emission enhancement (AIEE), are analyzed in direct correlation with molecular design strategies and structure-property relationships. A comparative synthesis of key analytical figures of merit, encompassing detection limits (reaching sub-nanomolar levels in selected systems), selectivity profiles, response kinetics, solvent compatibility, reversibility, and real-sample applicability, reveals marked progress in probe sophistication and practical performance. Nonetheless, critical limitations persist, including susceptibility to imine hydrolysis under physiological and aqueous conditions, inadequate water solubility, and predominantly irreversible binding modes. Future development should prioritise computationally guided probe design, nanomaterial-integrated architectures, and miniaturised solid-state platforms to advance Schiff base chemosensors toward translational deployment in clinical diagnostics, environmental surveillance, food safety screening, and live-cell bioimaging.