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Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity

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Abstract

It is now well established that ruthenium complexes are attractive alternatives to platinum-based anticancer agents. Most of the ruthenium compounds currently under investigation contain a single metal center. The synthesis of multinuclear analogues may provide access to novel complexes with enhanced biological activity. In this work, we have synthesized a set of three trinuclear complexes containing organometallic ruthenium fragments—(arene)RuCl—coordinated to a 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine core [(Arene = benzene (2), p-cymene (1), or hexamethylbenzene (3)]. The interaction of the complexes with DNA was extensively studied using a variety of biophysical probes as well as by molecular docking. The complexes bind strongly to DNA with apparent binding constants ranging from 2.20 to 4.79 × 104 M−1. The binding constants from electronic absorption titrations were an order of magnitude greater. The mode of binding to the nucleic acid was not definitively determined, but the evidence pointed to some kind of non-specific electrostatic interaction. None of the complexes displayed any significant antimicrobial activity against the organisms that were studied and exhibited anticancer activity only at high (> 100 μM) concentration.

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Acknowledgements

MBN would like to thank the Department of Natural Sciences at the University of Virginia’s College at Wise, for a Fellowship in the Natural Sciences to carry out this work. The authors would also like to thank CO-ADD (University of Queensland) for the antimicrobial assays along with Eastman Chemicals, Kingsport, TN, and Bruker Biospin for the NMR analyses. AAH would like to thank the National Science Foundation (NSF) for the NSF CAREER Award, as this material is based upon work partially supported by the NSF under CHE-1431172 (Formerly CHE-1151832). AAH would also like to thank Old Dominion University’s Faculty Proposal Preparation Program (FP3) and the University of North Texas Health Science Center, Texas Center for Health Disparities Research Pilot Award, Steps Toward Academic Research (STAR) Fellowship Program (award numbers: R10078-2018-0053 and R10078-2018-0108) for also supporting this work.

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Authors and Affiliations

  1. Department of Natural Sciences, The University of Virginia’s College at Wise, 1 College Avenue, Wise, VA, 24293, USA

    Floyd A. Beckford & Madison B. Niece

  2. Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA

    Brittany P. Lassiter & Stephen J. Beebe

  3. Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA, 23529-0126, USA

    Alvin A. Holder

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  1. Floyd A. Beckford
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Correspondence to Floyd A. Beckford.

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Beckford, F.A., Niece, M.B., Lassiter, B.P. et al. Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity. J Biol Inorg Chem 23, 1205–1217 (2018). https://doi.org/10.1007/s00775-018-1599-8

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