Novel R3M (M = Si, Ge) substituted furan and thiophene-derived aldimines: Synthesis, electrochemistry, and biological activity

Abstract

New furan and thiophene derivatives of aldimines o-HO-C 6 H 4 N]CHC 4 H 4 X(R) (X ¼ O, S; R ¼ H, SiMe 3 , SiEt 3 , GeMe 3 , GeEt 3 ) were synthesized by condensation of o-aminophenol with the substituted aldehyde precursor. Their structure, electrochemical reduction/oxidation (in CH 3 CN/0.1 M Bu 4 NPF 6 ), frontier orbital energies, and cytotoxicity have been studied. Their electrochemical redox potentials E p show good correlation with the corresponding orbital energies and the difference E p ox e E p red corresponds well to their orbital hardness.These new compounds have a pronounced cytotoxicity toward cancer cells of human fibrosarcoma HT-1080 and mouse hepatoma MG-22A (IC 50 y 1e8 mg ml À1 ) that can be modulated by introducing a Me 3 M substituent into the fifth position of the heterocycle (e.g., IC 50 (Me 3 Si)/IC 50 (H) ! 50). R 3 M-substitution reduces the orbital hardness of the aldimines studied and facilitates oxidation, promoting their oxidative metabolism. The neighboring group effect in the a-Me 3 Si-substituted thiophene derivative favors S-oxidation, which supposedly makes its metabolic mechanism different compared to R 3 Msubstituted furan series (or for M ¼ Ge in the thiophene series). Interestingly, SiMe 3 and GeMe 3 groups in both heterocyclic series (furan and thiophene) cause opposite trends in cytotoxicity, while the silyl group increases it, the germyl group decreases it.

Catechol‐ and Phenol‐Containing Thio‐Schiff Bases: Synthesis, Electrochemical Properties and Biological Evaluation

“…This peak is irreversible for 6 that indicates the following chemical stage. The first oxidation potentials of 5 and 6 are significantly shifted to the cathodic region, in contrast to the unsubstituted imino‐phenols [20] . The second oxidation peak in both cases is quasi‐reversible (I c /I a =0.8 and 0.6), and is observed at identical values of the oxidation potential.…”

“…The first oxidation potentials of 5 and 6 are significantly shifted to the cathodic region, in contrast to the unsubstituted imino-phenols. [20] The second oxidation peak in both cases is quasi-reversible (I c /I a = 0.8 and 0.6), and is observed at identical values of the oxidation potential. This fact suggests the formation of relatively stable and structurally similar intermediates.…”