A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin.
The synthesis and X-ray structure (as the tetrahydrate) of the platinum(IV) complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(NH(3))(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)(NH(3))(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 intermolecular 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(II) 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.
School of Chemistry, The University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3 JJ, UK.
Fiona S
FS
Mackay
Julie A
JA
Woods
Harry
H
Moseley
James
J
Ferguson
Alice
A
Dawson
Simon
S
Parsons
Peter J
PJ
Sadler
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D002945:Cisplatin / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D017319:Photosensitizing Agents / Q000737:chemistry / Q000633:toxicity*
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D002945:Cisplatin