Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2′-bipyridine and ethylenediamine and their interaction with human serum albumin

Complex formation equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (eta(5)-pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous solution via pH-potentiometry, H-1 NMR spectroscopy, and UV-vis spectrophotometry in the absence and presence of chloride ions. The structure of [RhCp star(en)Cl]ClO4 (Cp-star, pentamethylcyclopentadienyl) was also studied by single-crystal X-ray diffraction. pK, values of 8.56 and 9.58 were determined for [RhCp star(bpy)(H2O)](2+) and [RhCp star(en)(H2O)](2+), respectively resulting in the formation of negligible amount of mixed hydroxido complexes at pH 7.4. Stability and the H2O/Cl- co-ligand exchange constants of bpy and en complexes considerably exceed those of the bidentate O-donor deferiprone. The strong affinity of the bpy and en complexes to chloride ions most probably contributes to their low antiproliferative effect. Interactions between human serum albumin (HSA) and [RhCp star(H2O)(3)](2+), its complexes formed with deferiprone, bpy and en were also monitored by H-1 NMR spectroscopy, ultrafiltration/UV-vis and spectrofluorometry. Numerous binding sites (>= 8) are available for [RhCr(H20)3]S+; and the interaction takes place most probably via covalent bonds through the imidazole nitrogen of His. According to the various fluorescence studies [RhCp star(H2O)(3)](2+) binds on sites land II, and coordination of surface side chain donor atoms of the protein is also feasible. The binding of the bpy and en complex is weaker and slower compared to that of [RhCp star(H2O)(3)](2+), and formation of ternary HSA-RhCr-ligand adducts was proved. In the case of the deferiprone complex, the RhCp star fragment is cleaved off when HSA is loaded with low equivalents of the compound. (C) 2015 Elsevier Inc. All rights reserved.