期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 147, 期 -, 页码 71-84出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2014.12.021
关键词
Vanadium; Ceftriaxone; Blood; EPR spectroscopy; Density functional theory calculations
资金
- Fondazione Banco di Sardegna [U924.2014/AI.807.MGB, 2014.0443]
The coordination mode and geometry in aqueous solution of oxidovanadium(IV) complexes formed by a third-generation cephalosporin, ceftriaxone (H(3)cef), were studied by spectroscopic (EPR, electron paramagnetic resonance), pH-potentiometric and computational (DFT, density functional theory) methods. The behavior of the model systems containing 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro-1,2,4-triazine-5(2H)-one (H(2)hmtdt) and 3-benzylthio-6-hydroxy-2-methyl-1,2,4-triazine-5(2H)-one (Hbhmt) was examined for comparison. The stability of the tautomers of ceftriaxone and 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro-1,2,4-triazine-5(2H)one in the neutral, mono- and hi-anionic form was calculated by DFT methods, both in the gas phase and in aqueous solution, and the electron density on the oxygen atoms of the hydroxytriazinone ring was related to the plc of the ligands. The data demonstrate that ceftriaxone coordinates (VO2+)-O-IV forming mono- and bis-chelated complexes with (O-ket,O-) donor set and formation of five-membered chelate rings. The geometry of the his-chelated complex, cis-[VO(Hcef)(2)(H2O)](2), is cis-octahedral and this species can deprotonate, around physiological pH, to form the corresponding mono-hydroxido cis-[VO(Hcef)(2)(OH)](13-). The interacLtion of cis-[VO(Hcef)(2)(H2O)](2-) with apo-transferrin (apo-hTf) was studied and the results suggest that (VO2+)-O-iv distributes between (VO)apohTf/(VO)(2)apo-hTf and cis-[VO(Hcef)(2)(H2O)](2-), whereas mixed complexes are not formed for charge and steric effects. The interaction of cis-[VO(Hcef)(2)(H2O)](2-) with red blood cells shows that ceftriaxone helps (VO2+)-O-IV ion to cross the erythrocyte membrane. Inside the cell cis-[VO(Hcef)(2)(H2O)](2-) decomposes and the same species formed by inorganic (VO2+)-O-IV are observed. The relationship between the biotransformation in the plasma and red blood cells and the potential pharmacological activity of (VO2+)-O-IV species of ceftriaxone is finally discussed. (C) 2015 Elsevier Inc. All rights reserved.
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