Highly diastereoselective self-assembly reactions give both enantiomers (Λ and Δ) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution; the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Λ enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Λ enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s); while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Λ enantiomer, Δ-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.

Beijing Area Major Laboratory of Peptide and Small Molecular Drugs Engineering Research Centre of Endogenous Prophylactic of Ministry of Education of China School of Pharmaceutical Sciences Capital Medical University Beijing 100069 China

College of Chemistry State Key Laboratory of Elemento Organic Chemistry Nankai University Tianjin 300071 China

Czech Academy of Sciences Institute of Biophysics Brno Czech Republic

Department of Biophysics Palacky University Olomouc Czech Republic

Department of Chemistry Hong Kong Baptist University Kowloon Tong Hong Kong SAR China

Department of Chemistry University of Warwick Coventry CV4 7AL UK

Department of Pharmacy University of Huddersfield Huddersfield HD1 3DH UK

Faculty of Science Department of Biochemistry Masaryk University Brno Czech Republic

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