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Interaction of pharmacologically active pyrone and pyridinone vanadium(IV,V) complexes with cytochrome c
No full textThe interaction between cytochrome c (Cyt) and potential vanadium drugs, formed by 1,2-dimethyl-3-hydroxy-4 (1H)-pyridinonate (dhp) and maltolate (ma), was studied by ElectroSpray Ionization-Mass Spectrometry (ESIMS). Since under physiological conditions redox processes are possible, the binding of the complexes in the oxidation state +IV and +V, [(VO)-O-IV(dhp)(2)], [(VO)-O-IV(ma)(2)], [(VO2)-O-V(dhp)(2)](-) and [(VO2)-O-V(ma)(2)](-), was examined. In all systems V-IV,V-V-L-Cyt adducts are observed, their formation depending on V oxidation state, ligand L and metal concentration. The larger stability of vanadium(IV) than vanadium(V) complexes favors the interaction of the moieties (VOL2)-O-IV and (VOL+)-O-IV with V-IV, while with V-V adducts with (VO2L)-O-V and (VO2+)-O-V fragments are observed. The analysis of the protein structure suggests that Glu4, Glu21, Asp50, Glu62, Glu66 and Glu104 are the most plausible candidates for monodentate coordination, while the couples (Asp2, Glu4), (Glu92, Asp93) and (His33, Glu104) for bidentate binding. The values of E-1/2 for [(VO)-O-IV(dhp)(2)] and [(VO)-O-IV(ma)(2)], measured by cyclic voltammetry (CV), 0.53 V and 0.60 V vs. standard hydrogen electrode, indicate that the oxidation of V-IV to V-V is possible. The presence of a protein can alter the redox behavior and stabilize one of the states, V-IV or V-V. Overall, the data reinforce the conclusion that, for V drugs, the biotransformation is fundamental to explain their biological action and the analysis should not be limited to the ligand exchange and hydrolysis but also include the redox processes, and that a mixture of V-IV and V(V )species, V-IV,V-V-L-Protein and VIV,V-Protein, could be responsible of the pharmacological effects
Covalent and non-covalent binding in vanadium-protein adducts
Full text linkThe ESI-MS and EPR results obtained during the study of systems containing vanadium-protein adducts have been explained integrating the spectrometric and spectroscopic responses with molecular modelling simulations. The representative systems formed by the potential antibacterial drug [VIVO(nalidixato)2(H2O)] with lysozyme and cytochrome c were fully characterized, interpreting the ESI-MS and EPR signals as the result of covalent and non-covalent binding. This behaviour should be considered for all metal-protein systems, and instrumental techniques - if necessary - should be coupled with modelling to achieve full characterization of the types of binding
Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 3. Antioxidant properties and radical production capability
No full textThe radical production capability and the antioxidant properties of some VIVO complexes formed by flavonoid ligands were examined. In particular, the bis-chelated species of quercetin (que), [VO(que)2]2 -, and morin (mor), [VO(mor)2], were evaluated for their capability to reduce the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and produce the hydroxyl radical •OH by Fenton-like reactions, where the reducing agent is VIVO2 +. The results were compared with those displayed by other VIVO complexes, such as [VO(H2O)5]2+, [VO(acac)2] (acac = acetylacetonate) and [VO(cat)2]2 - (cat = catecholate). The capability of the VIVO flavonoids complexes to reduce DPPH is much larger than that of the VIVO species formed by non-antioxidant ligands and it is due mainly to the flavonoid molecule. Through the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trapping assay of the hydroxyl radical it was possible to demonstrate that in acidic solution VIVO2+ has an effectiveness in producing •OH radicals comparable to that of Fe2+. When VIVO complexes of flavonoids were taken into account, the amount of hydroxyl radicals produced in Fenton-like reactions depends on the specific structure of the ligand and on their capability to reduce H2O2 to give •OH. Both the formation of reactive oxygen species (ROS) under physiological conditions by VIVO complexes of flavonoid ligands and their radical scavenging capability can be put in relationship with their antitumor effectiveness and it could be possible to modulate these actions by changing the features of the flavonoid coordinated to the VIVO2+ ion, such as the entity, nature and position of the substituents and the number of phenolic groups
Synthesis, crystal structures, EPR and DFT studies of first row transition metal complexes of lignin model compound ethylvanillin
No full textThe transition metal complexes of ethylvanillin [Mn(L) 2 (H 2 O) 2 ] (1), [Co(L) 2 (H 2 O) 2 ] (2), [Ni(L) 2 (H 2 O) 2 ] (3),
and [Zn(L) 2 (H 2 O) 2 ] (4) have been synthesized. The geometric and electronic structure of 1, 2, 3 and 4 has
been solved by X-ray diffraction analysis and EPR spectroscopy. They are octahedral complexes with a cis
arrangement of the two water molecules. All the structures were calculated by DFT methods at the level
of theory B3P86/6-311g. The EPR spectra of 1 are isotropic both at 298 and 77 K with g values at
2.034 ± 0.010 and 2.040 ± 0.010, respectively indicating Mn(II) ion (3d 5 ) with a S = 5/2 spin. 1 shows a
hyperfine structure with six strong absorptions, corresponding to the |?1/2, m> ? |1/2, m> ‘allowed’
transitions ( D M = ±1, D m = 0), and five pairs of ‘forbidden’ absorptions ( D M = ±1, D m = ±1), between
the D m = 0 hyperfine transitions in an organic solvent such as DMF, DMSO and CH 3 CN. EPR spectroscopy
and DFT calculations suggest that in the temperature range 77–298 K 2 presents a high-spin S = 3/2 state,
whereas the low-spin state S = 1/2 begins to be populated at temperatures higher than 77 K (liquid nitro-
gen temperature). In 3, the weak signal due to a small amount of an octahedral Ni(III) complex (NiL 3 ), is
characterized by a rhombic spectrum. DFT simulations on 4 indicate that the octahedral structure with a
cis arrangement of the two water ligands is more stable than the octahedral one with a trans arrangement
and the tetrahedral geometry
Complex formation between [(η6-p-cym)Ru(H2O)3]2+ and oligopeptides containing three histidyl moieties
No full textIn order to model the metal ion binding capabilities of high molecular mass components of blood the interaction between [(η6-p-cym)Ru(H2O)3]2+ and terminally protected oligopeptides containing three histidyl moieties (Ac-HHH-NH2, Ac-HAHH-NH2, Ac-HAHAH-NH2 and Ac-H*AH*AH*-NH2, where A = L-alanyl, H = L-histidyl, H* = N3-methyl-L-histidyl) were studied by pH-potentiometric, ESI-TOF-MS, circular dichroism and NMR methods at an ionic strength of 0.20 M KCl or KNO3 as well as using density functional theory (DFT) calculations. Protonation constants of the novel peptides are reported. Although for Ac-HHH-NH2 the immediate formation of precipitation with [(η6-p-cym)Ru(H2O)3]2+ hindered any further solution investigations results of the detailed NMR and MS studies revealed that the other three ligands coordinate to the metal ion in rather slow processes via the imidazole moieties forming [(η6-p-cym)RuL]2+ (L = oligopeptide) type species in the slightly acidic, neutral pH-range. At pH ∼7.5 identical binding mode of Ac-HAHH-NH2 and Ac-HAHAH-NH2 in the [(η6-p-cym)RuL]2+ via three imidazole nitrogens was found hindering completely the hydrolysis of the metal ion even at 1:1 metal ion to ligand ratio. At elevated pH MS evidences support the involvement of amide-N donor(s) in metal ion binding too beside partial hydrolysis. 0.20 M KCl medium was found to hinder effectively the hydrolytic processes of the metal ion in the basic pH-range without altering the coordination of the imidazole side chains. Both NMR and DFT results support the imidazole-N1 (“far” or “τ”) over the N3 (“near” or “π”) coordination of the histidyl side chains of all these oligopeptides to the organometallic ruthenium(II) cation
Nonoxido VIV complexes: Prediction of the EPR spectrum and electronic structure of simple coordination compounds and amavadin
No full textDensity functional theory (DFT) calculations of the 51V hyperfine coupling (HFC) tensor A have been completed for 20 "bare" VIV complexes with different donor sets, electric charges, and coordination geometries. Calculations were performed with ORCA and Gaussian software, using functionals BP86, TPSS0, B1LYP, PBE0, B3LYP, B3P, B3PW, O3LYP, BHandHLYP, BHandH, and B2PLYP. Among the basis sets, 6-311g(d,p), 6-311++g(d,p), VTZ, cc-pVTZ, def2-TZVPP, and the "core properties" CP(PPP) were tested. The experimental Aiso and Ai (where i = x or z, depending on the geometry and electronic structure of VIV complex) were compared with the values calculated by DFT methods. The results indicated that, based on the mean absolute percentage deviation (MAPD), the best functional to predict Aiso or Ai is the double hybrid B2PLYP. With this functional and the basis set VTZ, it is possible to predict the Aiso and Az of the EPR spectrum of amavadin with deviations of -1.1% and -2.0% from the experimental values. The results allowed us to divide the spectra of nonoxido VIV compounds in three types - called "type 1", "type 2", and "type 3", characterized by different composition of the singly occupied molecular orbital (SOMO) and relationship between the values of Ax, Ay, and Az. For "type 1" spectra, Az ≫ Ax ≈ Ay and Az is in the range of (135-155) × 10-4 cm-1 for "type 2" spectra, Ax ≈ Ay ≫ Az and Ax ≈ Ay are in the range of (90-120) × 10-4 cm-1 and for the intermediate spectra of "type 3", Az > Ay > Ax or Ax > Ay > Az, with Az or Ax values in the range of (120-135) × 10-4 cm-1. The electronic structure of the VIV species was also discussed, and the results showed that the values of Ax or Az are correlated with the percent contribution of V-dxy orbital in the SOMO. Similarly to VIVO species, for amavadin the SOMO is based mainly on the V-dxy orbital, and this accounts for the large experimental value of Az (153 × 10-4 cm-1)
Influence of temperature on the equilibria of oxidovanadium(IV) complexes in solution
No full textThe equilibria in the solution of three different oxidovanadium(IV) complexes, VO(dhp)2 (dhp = 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonato), VO(ma)2 (ma = maltolato) and VO(pic)2(H2O) (pic = picolinato), were examined in the temperature range of 120-352 K through a combination of instrumental (EPR spectroscopy) and computational techniques (DFT methods). The results revealed that a general equilibrium exists: VOL2 + H2O ⇄ cis-VOL2(H2O) ⇄ trans-VOL2(H2O), where cis and trans refer to the relative position of H2O and the oxido ligand. The equilibrium is more or less shifted to the right depending on the ligand, the temperature, the ionic strength and the coordinating properties of the solvent. With VO(dhp)2, only the square pyramidal species exists at 298 K in aqueous solution, while at 120 K the cis- and trans-VO(dhp)2(H2O) species are also present. The complex of maltol exists almost exclusively in the form cis-VO(ma)2(H2O) in aqueous solution at 298 K, while the trans species can be revealed only at higher temperatures, where the EPR linewidth significantly decreases. The equilibria involving 1-methylimidazole (MeIm), a model for the side chain His coordination, are also influenced by temperature, with its coordination being favored by decreasing the temperature. The implications of these results in the study of the (vanadium complex)-protein systems are discussed and the interaction with myoglobin (Mb) is examined as a representative example
Temperature and solvent structure dependence of VO2+ complexes of pyridine-N-oxide derivatives and their interaction with human serum transferrin
No full textThe behaviour of the systems formed by VO2+, 2-hydroxypyridine-N-oxide (Hhpo) and 2-mercaptopyridine-N-oxide (Hmpo) was studied both in solution and in the solid state through the combined application of spectroscopic (EPR and UV-Vis spectroscopy) and DFT methods. The geometry of solid bis-chelated complexes [VOL2], with L = hpo and mpo, is square pyramidal, but it can change to cis-[VOL2S], where S is a solvent molecule, when these are dissolved in a coordinating solvent. The equilibrium between the square pyramidal and cis-octahedral forms is strongly affected by solvent and temperature. At room temperature, the predominant species is [VOL2], which gives a pink colour to the solutions; at lower temperatures, the equilibrium is shifted-partially or completely-toward the formation of cis-[VOL2S], which is green. In an acidic environment and in the presence of an excess of ligand, [VOL2] can transform into the tris-chelated complex [VL3](+), in which vanadium loses the oxido ligand and adopts a hexa-coordinated geometry intermediate between octahedral and trigonal prismatic. 1-Methylimidazole (1-MeIm), which represents a model for His-N coordination, forms mixed complexes with stoichiometry cis-[VOL2(1-MeIm)], occupying an equatorial position. In the ternary systems VO2+-Hhpo-hTf and VO2+-Hmpo-hTf at room temperature and pH 7.4, besides (VO)hTf and (VO)(2)hTf, the mixed species cis-VO(hpo)(2)(hTf) and VO(mpo)(hTf) are observed, with the equatorial binding of an accessible histidine residue. Finally, the contribution of the N-oxide group to (51)VA(z) and A(iso) hyperfine coupling constants, which can be important in the characterisation of similar species, is discussed
Spectroscopic/Computational Characterization and the X-ray Structure of the Adduct of the VIVO-Picolinato Complex with RNase A
Full text linkThe structure, stability, and enzymatic activity of the adduct formed upon the reaction of the V-picolinato (pic) complex [VIVO(pic)2(H2O)], with an octahedral geometry and the water ligand in cis to the V=O group, with the bovine pancreatic ribonuclease (RNase A) were studied. While electrospray ionization-mass spectrometry, circular dichroism, and ultraviolet-visible absorption spectroscopy substantiate the interaction between the metal moiety and RNase A, electron paramagnetic resonance (EPR) allows us to determine that a carboxylate group, stemming from Asp or Glu residues, and imidazole nitrogen from His residues are involved in the V binding at acidic and physiological pH, respectively. Crystallographic data demonstrate that the VIVO(pic)2 moiety coordinates the side chain of Glu111 of RNase A, by substituting the equatorial water molecule at acidic pH. Computational methods confirm that Glu111 is the most affine residue and interacts favorably with the OC-6-23-Δenantiomer establishing an extended network of hydrogen bonds and van der Waals stabilizations. By increasing the pH around neutrality, with the deprotonation of histidine side chains, the binding of the V complex to His105 and His119 could occur, with that to His105 which should be preferred when compared to that to the catalytically important His119. The binding of the V compound affects the enzymatic activity of RNase A, but it does not alter its overall structure and stability
Interaction of V(V) complexes formed by picolinic and pyrazinecarboxylic acid derivatives with red blood cells
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