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Redox properties of ferrocene-substituted nucleobases

Ferrocene-substituted nucleobases have diverse biological and electrochemical properties since they combine biogenic and redox-active parts. [1] Ferrocene undergoes a reversible one-electron oxidation producing a stable ferrocenium cation and serves as an internal standard for electrochemistry in non-aqueous solution. Ferrocenyl compounds are known to exhibit anticancer activity through a redox mechanism by generating reactive oxygen species – hydroxyl radicals (•OH) causing the DNA cleavage and oxidative stress. [2] In continuation of our work [3, 4] we synthesized a series of ferrocene- substituted purine- and pyrimidine-nucleobase derivatives and measured their redox potential by the cyclic voltammetry in dichloromethane. All measured compounds showed a reversible oneelectron oxidation in the range of 300-450 mV. Interestingly, we can easily distinguish the two ferrocenoyl-purine regioisomers, N7 and N9, simply by the redox potential value. In the case of bis- ferrocene substituted compounds the two electrochemical events were expected, but only one simultaneous process was observed. In order to examine the tendency of ferrocene-nucleobase conjugates to produce reactive oxygen species (ROS), we carried out an acellular screening with DCFH assay in DMSO. We found that the nucleobases coupled with ferrocene generate ROS, while neither ferrocene itself nor the nucleobases were active. By changing the substituents on the purine ring, one can significantly influence the ROS generation of ferrocene-substituted nucleobases. References: [1] K. Kowalski, Coord. Chem. Rev. 2016, 317, 132. [2] M. Patra, G. Gasser, Nat. Rev. Chem. 2017, 1, 1. [3] J. Lapić, V. Havaić, D. Šakić, K. Sanković, S. Djaković, V. Vrček, Eur. J. Org. Chem. 2015, 5424. [4] M. Toma, L. Božičević, J. Lapić, S. Djaković, D. Šakić, T. Tandarić, R. Vianello, V. Vrček, J. Org. Chem. 2019, 84, 19, 12471.

ferrocene ; nucleobase ; redox ; electrochemistry ; DFT ; ROS

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