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 [1H, 15N] HSQC NMR Spectra
Author(s)
Ruhayel, Rasha A
Corry, Ben
Braun, Carlos
Thomas, Donald S
Berners-Price, Susan J
Farrell, Nicholas P
Griffith University Author(s)
Year published
2010
Metadata
Show full item recordAbstract
Two-dimensional (2D) [1H, 15N] heteronuclear single-quantum coherence (HSQC) NMR experiments of the kinetics of aquation and sulfation of the dinuclear platinum anticancer complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]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 (kH) is higher than that previously found in the presence of phosphate, but the anation rate constants are ...
View more >Two-dimensional (2D) [1H, 15N] heteronuclear single-quantum coherence (HSQC) NMR experiments of the kinetics of aquation and sulfation of the dinuclear platinum anticancer complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]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 (kH) 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 (kL) 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 [1H, 15N] 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.
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View more >Two-dimensional (2D) [1H, 15N] heteronuclear single-quantum coherence (HSQC) NMR experiments of the kinetics of aquation and sulfation of the dinuclear platinum anticancer complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)]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 (kH) 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 (kL) 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 [1H, 15N] 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.
View less >
Journal Title
Inorganic Chemistry
Volume
49
Issue
23
Funder(s)
ARC
Grant identifier(s)
DP1095383
Subject
Inorganic chemistry
Bioinorganic chemistry
Physical chemistry
Other chemical sciences