Mirror-Image Organometallic Osmium Arene Iminopyridine Halido Complexes Exhibit Similar Potent Anticancer Activity

Four chiral OsII arene anticancer complexes have been isolated by fractional crystallization. The two iodido complexes, (SOs,SC)‐[Os(η6‐p‐cym)(ImpyMe)I]PF6 (complex 2, (S)‐ImpyMe: N‐(2‐pyridylmethylene)‐(S)‐1‐phenylethylamine) and (ROs,RC)‐[Os(η6‐p‐cym)(ImpyMe)I]PF6 (complex 4, (R)‐ImpyMe: N‐(2‐pyridylmethylene)‐(R)‐1‐phenylethylamine), showed higher anticancer activity (lower IC50 values) towards A2780 human ovarian cancer cells than cisplatin and were more active than the two chlorido derivatives, (SOs,SC)‐[Os(η6‐p‐cym)(ImpyMe)Cl]PF6, 1, and (ROs,RC)‐[Os(η6‐p‐cym)(ImpyMe)Cl]PF6, 3. The two iodido complexes were evaluated in the National Cancer Institute 60‐cell‐line screen, by using the COMPARE algorithm. This showed that the two potent iodido complexes, 2 (NSC: D‐758116/1) and 4 (NSC: D‐758118/1), share surprisingly similar cancer cell selectivity patterns with the anti‐microtubule drug, vinblastine sulfate. However, no direct effect on tubulin polymerization was found for 2 and 4, an observation that appears to indicate a novel mechanism of action. In addition, complexes 2 and 4 demonstrated potential as transfer‐hydrogenation catalysts for imine reduction. Mirror images: Two chiral OsII arene iminopyridine complexes have been isolated by fractional crystallization: (SOs,SC)‐[Os(η6‐p‐cym)(ImpyMe)I]PF6 and (ROs,RC)‐[Os(η6‐p‐cym)(ImpyMe)I]PF6. Their X‐ray structures, as well as those of the chlorido analogues, have been determined (see graphic). The complexes exhibit high anticancer activity towards human ovarian, breast, and melanoma cancer cells, and have a mechanism of action distinctly different from cisplatin. They also show potential as transfer‐hydrogenation catalysts for imine reduction.