A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin

Fiona S. Mackay, Julie A. Woods, Harry Moseley, James Ferguson, Alice Dawson, Simon Parsons, Peter J. Sadler

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    Abstract

    The synthesis and X-ray structure (as the tetrahydrate) of the platinum(IV) complex trans, trans, trans[Pt(N-3)(2)(OH)(2)(NH3)(2)] 3 are described and its photochemistry and photobiology are compared with those of the cis isomer cis,trans,cis-[Pt(N-3)(2)(OH)(2)(NH3)(2)] 4. Complexes 4 and 3 are potential precursors of the anticancer drug cisplatin and its inactive trans isomer transplatin, respectively. The trans complex 3 is octahedral, contains almost linear azide ligands, and adopts a layer structure with extensive inter-molecular hydrogen bonding. The intense azide-to-platinum(iv) charge-transfer band of complex 3 (285 nm; epsilon = 19 500 m(-1) cm(-1)) is more intense and bathochromically shifted relative to that of the cis isomer 4. In contrast to transplatin, complex 3 rapidly formed a platinum(n) bis(5'-guanosine monophosphate) (5'-GMP) adduct when irradiated with UVA light, and did not react in the dark. Complexes 3 and 4 were non-toxic to human skin cells (keratinocytes) in the dark, but were as cytotoxic as cisplatin on irradiation for a short time (50 min). Damage to the DNA of these cells was detected by using the "comet" assay. Both trans- and cis-diammine platinum(iv) diazide complexes therefore have potential as photochemotherapeutic agents.

    Original languageEnglish
    Pages (from-to)3155-3161
    Number of pages7
    JournalChemistry: a European Journal
    Volume12
    Issue number11
    DOIs
    Publication statusPublished - 2006

    Cite this

    Mackay, F. S., Woods, J. A., Moseley, H., Ferguson, J., Dawson, A., Parsons, S., & Sadler, P. J. (2006). A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin. Chemistry: a European Journal, 12(11), 3155-3161. https://doi.org/10.1002/chem.200501601