Synthesis, characterization and effect of the fluorine substitution on the redox reactivity and in vitro anticancer behaviors of N-polyfluorophenyl-3,5-di-tert-butylsalicylaldimines and their Cu(II) complexes

• A series of new polyfluorinated bis(N-C6FnH5−n-3,5-tBu2-salicylaldiminato)Cu(II) complexes have been prepared.
• Conversions of generated Cu(II)–bisphenoxyls to another radicals have been observed.
• The effect of fluorine atoms on the redox behaviors of Cu(II) complexes was observed.
• As the number of F atoms increases in ligands and complexes their IC50 values decrease.
• Crystal structure of bis(N-C6F4H-3,5-tBu2-salicylaldiminato)Cu has been determined.

A series of new polyfluorinated bis(N-C6FnH5−n3,5-tBu2salicylaldiminato)Cu(II) [n = 2; 2,4-F2C6H3-3,5-DTBS (1), 2,5-F2C6H3-3,5-DTBS (2), 2,6-F2C6H3-3,5-DTBS (3); n = 3; 2,3,4-F3C6H2-3,5-DTBS (4), n = 4; 2,3,5,6-F4C6H-3,5-DTBS (5), n = 5; 2,3,4,5,6-F5C6-3,5-DTBS (6); where 3,5-DTBS is 3,5-tBu2salicylaldiminato] with N-polyfluorophenyl-3,5-di-tert-butylsalicylaldi-mines (HL1–HL6) have been synthesized. Their structure, chemical and electrochemical redox-reactivity as well as cytotoxic activity of these compounds were characterized by analytical, spectroscopic (UV/vis, FT-IR, 19F NMR and EPR), magnetic, CV techniques and MTT assay. The in situ UV/Vis study have shown that the redox behavior of 1–6 and their Cu–phenoxyl radicals (1
• +–6
• + and 1
•
• +–6
•
• +) depend on the number and positions of F atoms on the aniline ring as well as of the nature of solvent. The in vitro cytotoxic activity studies of HL1–HL6 and 1–6 against K562 cell lines indicate that the HL1, HL4–HL6 and their corresponding complexes (1, 4–6) exhibited higher cytotoxic activity than HL2, HL3 and their complexes. Compounds 1, 4 and 5 are more cytotoxic than their respective ligands.

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