A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin

TY - JOUR

T1 - A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin

AU - Mackay, Fiona S.

AU - Woods, Julie A.

AU - Moseley, Harry

AU - Ferguson, James

AU - Dawson, Alice

AU - Parsons, Simon

AU - Sadler, Peter J.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1002/chem.200501601

DO - 10.1002/chem.200501601

M3 - Article

C2 - 16470886

SN - 0947-6539

VL - 12

SP - 3155

EP - 3161

JO - Chemistry: a European Journal

JF - Chemistry: a European Journal

IS - 11

ER -