Interaction of Cu(II) 3,5-diisopropylsalicylate with human serum albumin--an evaluation of spectroscopic data.
The copper(II) complex of 3,5-diisopropylsalicylate is a lipophilic water-insoluble binuclear complex, Cu(II)2(3,5-DIPS)4, that has attracted interest because of a wide range of pharmacological activities. This study was undertaken to examine bonding interactions between the complex and human serum albumin (HSA) to help elucidate the mode of transport of the complex in vivo. Electron paramagnetic resonance, numerical magnetic resonance and UV-visible absorption spectroscopic studies were performed using 200 microM aqueous solutions (pH 7.5) of HSA to which had been added up to three molar equivalents of CuCl2, CuSO4, or Cu(II)2(3,5-DIPS)4. Both EPR and UV-visible spectra demonstrated the presence of more than one copper bonding site on HSA, and proton NMR spectra showed that the 3,5-DIPS ligand is also bonded to HSA. These results indicate that there is no observable direct coordination of the ligand to copper in the presence of HSA, and that the majority of the copper and 3,5-DIPS bond to HSA at separate sites. Addition of solid Cu(II)2(3,5-DIPS)4 to HSA at pH 7.5 similarly resulted in spectra suggest that there are no ternary Cu(II)(3,5-DIPS), Cu(II)(3,5-DIPS)2, or Cu(II)2(3,5-DIPS)4 complexes formed with HSA. It is concluded that any ternary complexes formed in the presence of HSA are below the spectroscopic detection limits and represent less than 5% of the total copper.
Greenaway
F T
FT
Gustaf H. Carlson School of Chemistry, Clark University, Worcester, MA 01610, USA. fgreenaway@clarku.edu
Hahn
J J
JJ
Xi
N
N
Sorenson
J R
JR
D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D012459:Salicylates / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D046911:Macromolecular Substances; D012459:Salicylates; D012709:Serum Albumin; C030865:copper bis(3,5-diisopropylsalicylate)