Determination of the kinetic profile of a dinuclear platinum anticancer complex in the presence of sulfate: introducing a new tool for the expedited analysis of 2D [(1)H,( 15)N] HSQC NMR spectra.
Two-dimensional (2D) [(1)H, (15)N] heteronuclear single-quantum coherence (HSQC) NMR experiments of the kinetics of aquation and sulfation of the dinuclear platinum anticancer complex [{trans-PtCl(NH(3))(2)}(2)(μ-NH(2)(CH(2))(6)NH(2))](2+) (1,1/t,t, 1) in 15 mM sulfate solution are reported using conditions (298 K, pH 5.4) identical to those previously used for other anionic systems (phosphate and acetate), allowing for a direct comparison. Sulfate is the fourth most abundant anion in human plasma. The rate constant for the aquation step (k(H)) is higher than that previously found in the presence of phosphate, but the anation rate constants are similar. The rate constant for sulfate displacement of the aqua ligand (k(L)) is approximately three times higher than that of phosphate, and a further major difference between these two anions is the very high k(-L) for loss of sulfate, suggesting that when formed in plasma the sulfato species will be substitution labile. We also introduce a novel (free) plug-in, '2D NMR analysis', developed for the expedited integration and analysis of 2D [(1)H, (15)N] HSQC NMR spectra. We have found that this plug-in significantly reduces the amount of time taken in the analysis of experiments with no loss to the quality of the data.
School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
Rasha A
RA
Ruhayel
Ben
B
Corry
Carlos
C
Braun
Donald S
DS
Thomas
Susan J
SJ
Berners-Price
Nicholas P
NP
Farrell
D000970:Antineoplastic Agents / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D017671:Platinum Compounds / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D013431:Sulfates; D014867:Water