The biotransformation in the plasma and red blood cells of two potential antitumor V(IV)O complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5'-sulfonic acid or que(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 V(IV)O 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(mor(S))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 V(IV)O(2+) 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 V(IV)O 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 5.0×10(-4)M and incubation time in the range 0-160min. 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(que(S))2 do not transform, whereas VO(mor)2/VO(mor(S))2 give the partial formation of mixed species with hemoglobin (Hb) and other V(IV)O complexes.
Keywords: Blood plasma; EPR spectroscopy; Red blood cells; Secondary bonds; Vanadium.
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