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A spectroscopic study of the reaction of NAMI, a novel ruthenium(III)antiâneoplastic complex, with bovine serum albumin
- Messori, Luigi, Orioli, Pierluigi, Vullo, Daniela, Alessio, Enzo, Iengo, Elisabetta
- European journal of biochemistry 2000 v.267 no.4 pp. 1206-1213
- absorption, bovine serum albumin, histidine, hydrolysis, ions, mechanism of action, neoplasm cells, oxidation, ruthenium, sodium, spectroscopy
- The reaction of Na[transRuCl4Me2SO(Im)] (NAMI; where Im is imidazole), a novel antiâneoplastic ruthenium(III) complex, with BSA, was studied in detail by various physicoâchemical techniques. It is shown that NAMI, following chloride hydrolysis, binds bovine serum albumin tightly; spectrophotometric and atomic absorption data point out that up to five ruthenium ions are bound per albumin molecule when BSA is incubated for 24âh with an eightfold excess of NAMI. CD and electronic absorption results show that the various ruthenium centers bound to albumin exhibit well distinct spectroscopic features. The first ruthenium equivalent produces a characteristic positive CD band at 415ânm whereas the following NAMI equivalents produce less specific and less marked spectral effects. At high NAMI/BSA molar ratios a broad negative CD band develops at 590ânm. Evidence is provided that the bound ruthenium centers remain in the oxidation state +3. By analogy with the case of transferrins it is proposed that the BSAâbound ruthenium ions are ligated to surface histidines of the protein; results from chemical modification experiments with diethylpyrocarbonate seem to favor this view. Spectral patterns similar to those shown by NAMI are observed when BSA is reacted with two strictly related ruthenium(III) complexes Na[transRuCl4(Me2SO)2] and H(Im)[transRuCl4(Im)2] (ICR), implying a similar mechanism of interaction in all cases. It is suggested that the described NAMIâBSA adducts may form in vivo and may be relevant for the biological properties of this complex; alternatively NAMI/BSA adducts may be tested as specific carriers of the ruthenium complex to cancer cells. Implications of these findings for the mechanism of action of NAMI and of related ruthenium(III) complexes are discussed.