Colchicine red-ox chemistry revisited: Cathodic behavior and EPR observation of an intermediate radical anion

Colchicine (1), a potently antimitotic alkaloid and useful laboratory tool in cancer research, undergoes cathodic reduction in DMF forming and ESR-observable radical anion (1r) which is characterized by the isotropic hyperfine coupling constants 8.9, 4.3, 0.75, 0.49 and 0.48 G for H-8, H-12, OCH3, H-11 and H-4, respectively, and a much flattened troponoid ring. Assignments are aided by selective deuteriation of colchicine at C-8, C-11 and COCH3, as well as by spectral simulation and ab initio calculations of electron spin densities. Whether the colchicine radical anion may exist in nature is also discussed.