Behavior of the potential antitumor (VO)-O-IV complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies

摘要

The biotransformation in the plasma and red blood cells of two potential antitumor (VO)-O-IV complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5'-sulfonic acid or ques(S) and morin-5'-sulfonic acid or mor(S)) was studied by spectroscopic (EPR, Electron Paramagnetic Resonance) and computational (DFT, Density Functional Theory) methods. Que and que(S) form with (VO)-O-IV stable complexes, and in the systems with apo-transferrin (apo-hTf) and albumin (HSA) VO(que)(2) and VO(que(S))(2) remain unchanged. VO(mor)(2) and VO(mors)(2) undergo displacement reactions to give the partial formation of (VO)(x)(HSA) and (VO)(apo-hTf)/(VO)(2)(apo-hTf); moreover, mor(S) forms with apo-transferrin and albumin mixed species VO mor(S) apo-hTf and VO mor(S)-HSA. In the systems with apo-hTf and HSA anisotropic EPR spectra at room temperature are detected in which the protein is not directly coordinated to (VO2+)-O-IV ion. This is explained assuming that the bis-chelated complexes interact strongly with the proteins through a network of hydrogen bonds with the polar groups present on the protein surface. It is suggested that this "indirect" transport of (VO)-O-IV species could be common to all the species containing ligands which can interact with the blood proteins. Uptake experiments by red blood cells were also carried out, using vanadium concentration of 5.0 x 10(-4) M and incubation time in the range 0-160 min. VO(que)(2)/VO(que(S))(2) and VO(mor)(2)/VO(mor(S))(2) cross the erythrocytes membrane and in the cytosol VO(que)(2)/VO(ques)(2) do not transform, whereas VO(mor)(2)/VO(mor(S))(2) give the partial formation of mixed species with hemoglobin (Hb) and other (VO)-O-IV complexes. (C) 2015 Elsevier Inc All rights reserved.