1H NMR studies of reactions of copper complexes with human blood plasma and urine
Author(s)
Author(s)
Boyle, H. A.
McEwen, A. B.
Sadler, P. J.
Woodham, R. H.
Date Issued
1992
Publisher
Elsevier
Journal
Biochemical Pharmacology
Volume
43
Issue
2
Start page
137
End page
145
Abstract
Reactions of the copper complexes Cu(II)Cl2, [Cu(II)(EDTA)]2−, [Cu(II)2(DIPS)4] and [Cu(I)(DMP)2]+ (where DIPS is 3,5-diisopropylsalicylate and DMP is 2,9-dimethylphenanthroline) with human blood plasma and urine have been studied by 500MHz 1H NMR spectroscopy, and CD spectroscopy has been used to monitor the transfer of Cu(II) onto albumin in plasma. The rate of transfer of Cu(II) from [Cu(II)(EDTA)]2− onto albumin as measured by CD (T12 26 min, 0.5 mM Cu, 21°), was similar to the rate of Cu(II) binding to amino acids and citrate, and to the rate of formation of [Ca(II)(EDTA)]2− in plasma. Reactions of Cu(II)Cl2 and [Cu(II)2(DIPS)4] in plasma followed a similar course, but were more rapid. The latter complex also appeared to give rise to the displacement of lactate from protein binding. Reactions of copper complexes in plasma therefore involve a range of low Mr ligands as well as albumin, and the ligands play a major role in determining the kinetics of the reactions. These factors, as well as the partitioning of both complexes and displaced ligands into lipoproteins, are likely to play important roles in the molecular pharmacology of copper-containing drugs. In urine. His and formate were involved in EDTA and DIPS displacement from their respective copper complexes, and peaks for free DIPS and [Ca(II)(EDTA)]2− were observed. The complex (Cu(I)(DMP)2]+ appeared to be relatively stable in both plasma and urine.
SFU Affiliated Publication
No
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