Fluorine-enabled modulation of antioxidant activity in tetraaryl-dihydropyrrolopyrrole derivatives: design, synthesis, and structure–activity relationships
Monatshefte fur Chemie, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s00706-026-03470-5
- Dergi Adı: Monatshefte fur Chemie
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: Antioxidant activity, DPPH, Fluoro-substituted TAPP derivatives, Heteroaromatic compounds
- Gazi Üniversitesi Adresli: Evet
Özet
In this study, novel fluoro-substituted 1,2,4,5-tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole (TAPP) derivatives were designed and synthesized to investigate the influence of fluoro substitution on antioxidant activity. The aim of this work was to clarify how the positional effects of fluorine regulate electronic redistribution within the π-conjugated TAPP core and thereby affect radical scavenging behavior. A series of mono- and difluorinated derivatives bearing fluorine at different aromatic positions were prepared and evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. The results demonstrated that fluoro substitution significantly enhances antioxidant activity in a position-dependent manner. In particular, the 2- and 4-monofluorinated derivatives showed higher radical scavenging efficiencies than the reference antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), whereas the 3-monofluorinated derivative exhibited markedly lower activity. Among the difluorinated compounds, the 2,3-disubstituted derivative displayed the strongest antioxidant performance, which is attributed to the cooperative polarization effect of adjacent fluorine atoms and the preservation of molecular planarity. Overall, these findings indicate that fluorine modulates the antioxidant properties of the TAPP scaffold not only through its strong electronegativity but also through its positional and geometric arrangement. The ability of fluorine to participate in resonance interactions emerges as a key factor governing radical stabilization, highlighting fluorinated TAPP derivatives as promising, tunable antioxidant scaffolds for pharmaceutical applications.