Platinum(IV) analogues of AMD473 (cis-[PtCl2(NH3)(2-picoline)]): preparative, structural, and electrochemical studies.
The preparation and oxidation of the anticancer drug AMD473, cis-[PtCl2(NH3)(2-pic)] (2-pic = 2-methylpyridine), has been investigated. cis-[PtCl2(NH3)(2-pic)] is readily oxidized with peroxide to give the trans-dihydroxoplatinum(IV) complex cis,trans,cis-[PtCl2(OH)2(NH3)(2-pic)]. The crystal structure of this complex reveals that it is highly strained as a result of a steric clash between the methyl group of the 2-picoline ligand and an axial hydroxo ligand, with the Pt-N-C angle adjacent to this clash opened up to an unprecedented 138.6(6) degrees . Attempts at converting the dihydroxoplatinum(IV) complex to dichloro and diacetato analogues were unsuccessful with reaction with HCl leading to loss and protonation of the 2-picoline ligand to form the salt (2-picH)[PtCl5(NH3)] and the platinum(II) complex cis-[PtCl2(NH3)(2-pic)], both confirmed by crystallography. Electrochemical studies revealed that cis,trans,cis-[PtCl2(OH)2(NH3)(2-pic)] is reduced more readily (-714 mV vs Ag/AgCl) than its pyridine analogue cis,trans,cis-[PtCl2(OH)2(NH3)(pyridine)] (-770 mV vs Ag/AgCl) consistent with the steric clash in the former complex destabilizing the platinum(IV) oxidation state.
Battle
Andrew R
AR
Centre for Heavy Metals Research, School of Chemistry, University of Sydney, New South Wales 2006, Australia.
Choi
Robin
R
Hibbs
David E
DE
Hambley
Trevor W
TW
D004563:Electrochemistry; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*
D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II); D010984:Platinum