Spectrophotometric determination of antiradical potential of some 5-ylidene derivatives of rhodanine with a benzothiazole moiety in the molecules

Abstract

This study evaluates the antiradical potential of hybrid systems based on the benzothiazolerhodanine scaffold, the synthesis of which was previously reported. Such heterocycles are promising objects in medicinal chemistry due to their broad spectrum of biological activities and the possibility of versatile functional substitution. Establishing structure– activity relationships is essential for the rational design of potent antioxidants. Preliminary DPPH screening of N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol- 3(2H)-yl)acetamide and its 5-ylidene derivatives established that only the unsubstituted core heterocycle exhibits high activity comparable to ascorbic acid. Substitution at the 5-position of the rhodanine ring results in a decrease or loss of free radical scavenging activity. Among the derivatives, the compound bearing a 2,3-dichlorobenzylidene fragment exhibited the highest activity (62.85% at 2.0 mM), whereas other substituted benzylidene or isatinylidene derivatives displayed lower levels of inhibition. Modification of the 5-ylidene moiety appears to deactivate direct radical reactions. The observed effects are attributed to a complex interplay of electronic, thermodynamic, and delocalization factors, alongside limited steric accessibility of the reactive centers. Quantum chemical calculations using density functional theory for the most active heterocycle with a 5-unsubstituted rhodanine scaffold indicate that SPLET is the prevailing mechanism in methanol and substantiate its high radical scavenging activity in the DPPH test. The HAT pathway remains a plausible alternative under certain conditions or for different radicals, but it appears less favorable in MeOH. Similarly, SET-PT is thermodynamically possible but not initially favorable due to the higher ionization energy of the neutral molecule. Such synergy of approaches outlines the structure–activity relationship and provides a foundation for the rational design and targeted synthesis of the most promising agents for subsequent in vivo studies.