Nonoxido V^IV Complexes: Prediction of the EPR Spectrum and Electronic Structure of Simple Coordination Compounds and Amavadin

Density functional theory (DFT) calculations of the ⁵¹V hyperfine coupling (HFC) tensor <b>A</b> have been completed for 20 “bare” V^IV 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 <i>A</i>_iso and <i>A</i>_<i>i</i> (where <i>i</i> = <i>x</i> or <i>z</i>, depending on the geometry and electronic structure of V^IV 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 <i>A</i>_iso or <i>A_i</i> is the double hybrid B2PLYP. With this functional and the basis set VTZ, it is possible to predict the <i>A</i>_iso and <i>A</i>_<i>z</i> 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 V^IV 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 <i>A</i>_<i>x</i>, <i>A</i>_<i>y</i>, and <i>A</i>_<i>z</i>. For “type 1” spectra, <i>A</i>_<i>z</i> ≫ <i>A</i>_<i>x</i> ≈ <i>A</i>_<i>y</i> and <i>A</i>_<i>z</i> is in the range of (135–155) × 10^–4 cm^–1; for “type 2” spectra, <i>A</i>_<i>x</i> ≈ <i>A</i>_<i>y</i> ≫ <i>A</i>_<i>z</i> and <i>A</i>_<i>x</i> ≈ <i>A</i>_<i>y</i> are in the range of (90–120) × 10^–4 cm^–1; and for the intermediate spectra of “type 3”, <i>A</i>_<i>z</i> > <i>A</i>_<i>y</i> > <i>A</i>_<i>x</i> or <i>A</i>_<i>x</i> > <i>A</i>_<i>y</i> > <i>A</i>_<i>z</i>, with <i>A</i>_<i>z</i> or <i>A</i>_<i>x</i> values in the range of (120–135) × 10^–4 cm^–1. The electronic structure of the V^IV species was also discussed, and the results showed that the values of <i>A</i>_<i>x</i> or <i>A</i>_<i>z</i> are correlated with the percent contribution of V-d_<i>xy</i> orbital in the SOMO. Similarly to V^IVO species, for amavadin the SOMO is based mainly on the V-d_<i>xy</i> orbital, and this accounts for the large experimental value of <i>A</i>_<i>z</i> (153 × 10^–4 cm^–1)

Formation of New Non-oxido Vanadium(IV) Species in Aqueous Solution and in the Solid State by Tridentate (O, N, O) Ligands and Rationalization of Their EPR Behavior

The systems formed by the V^IVO²⁺ ion with tridentate ligands provided with the (O, N_imine, O) donor set were described. The ligands studied were 2,2′-dihydroxyazobenzene (Hdhab), α-(2-hydroxy-5-methylphenylimino)-<i>o</i>-cresol (Hhmpic), calmagite (H₂calm), anthracene chrome red A (H₃anth), calcon (H₂calc), and calconcarboxylic acid (H₃calc^C). They can bind vanadium with the two deprotonated phenol groups and the imine nitrogen to give (5,6)-membered chelate rings. The systems were studied with EPR, UV–vis and IR spectroscopy, pH-potentiometry, and DFT methods. The ligands form unusual non-oxido V^IV compounds both in aqueous solution and in the solid state. [V­(anthH_–1)₂]^4– and [V­(calmH_–1)₂]^2– (formed in water at the physiological pH) and [V­(dhabH_–1)₂] and [V­(hmpicH_–1)₂] (formed in the solid state in MeOH) are hexa-coordinated with geometry intermediate between the octahedron and the trigonal prism and an <i>unsymmetric facial</i> arrangement of the two ligand molecules. DFT calculations were used to predict the structure and ⁵¹V hyperfine coupling tensor <b>A</b> of the non-oxido species. The EPR behavior of 13 non-oxido V^IV species was put into relationship with the relevant geometrical parameters and was rationalized in terms of the spin density on the d_<i>xy</i> orbital. Depending on the geometric isomer formed (<i>meridional</i> or <i>facial</i>), d_<i>z</i>² mixes with the d_<i>xy</i> orbital, and this effect causes the lowering of the highest ⁵¹V <i>A</i> value

V^IVO Versus V^IV Complex Formation by Tridentate (O, N_arom, O) Ligands: Prediction of Geometry, EPR ⁵¹V Hyperfine Coupling Constants, and UV–Vis Spectra

Systems formed using the V^IVO²⁺ ion with tridentate ligands containing a (O, N_arom, O) donor set were described. Examined ligands were 3,5-bis­(2-hydroxyphenyl)-1-phenyl-1<i>H</i>-1,2,4-triazole (H₂hyph^Ph), 4-[3,5-bis­(2-hydroxyphenyl)-1<i>H</i>-1,2,4-triazol-1-yl]­benzoic acid (H₃hyph^C), 4-[3,5-bis­(2-hydroxyphenyl)-1<i>H</i>-1,2,4-triazol-1-yl]­benzenesulfonic acid (H₃hyph^S), and 2,6-bis­(2-hydroxyphenyl)­pyridine (H₂bhpp), with H₃hyph^C being an orally active iron chelator that is commercially available under the name Exjade (Novartis) for treatment of chronic iron overload arising from blood transfusions. The systems were studied using EPR, UV–Vis, and IR spectroscopies, pH potentiometry, and DFT methods. The ligands bind vanadium with the two terminal deprotonated phenol groups and the central aromatic nitrogen to give six-membered chelate rings. In aqueous solution the main species were the mono- and bis-chelated V^IVO complexes, whereas in the solid state neutral non-oxido V^IV compounds were formed. [V­(hyph^Ph)₂] and [V­(bhpp)₂] are hexacoordinated, with a geometry close to the octahedral and a meridional arrangement of the ligands. DFT calculations allow distinguishing V^IVO and V^IV species and predicting their structure, the ⁵¹V hyperfine coupling constant tensor <i><b>A</b></i>, and the electronic absorption spectra. Finally, EPR spectra of several non-oxido V^IV species were compared using relevant geometrical parameters to demonstrate that in the case of tridentate ligands the ⁵¹V hyperfine coupling constant is related to the geometric isomerism (meridional or facial) rather than the twist angle Φ, which measures the distortion of the hexacoordinated structure toward a trigonal prism

Elucidation of Binding Site and Chiral Specificity of Oxidovanadium Drugs with Lysozyme through Theoretical Calculations

This study presents an implementation of the protein–ligand docking program GOLD and a generalizable method to predict the binding site and orientation of potential vanadium drugs. Particularly, theoretical methods were applied to the study of the interaction of two V^IVO complexes with antidiabetic activity, [V^IVO­(pic)₂(H₂O)] and [V^IVO­(ma)₂(H₂O)], where pic is picolinate and ma is maltolate, with lysozyme (Lyz) for which electron paramagnetic resonance spectroscopy suggests the binding of the moieties VO­(pic)₂ and VO­(ma)₂ through a carboxylate group of an amino acid residue (Asp or Glu). The work is divided in three parts: (1) the generation of a new series of parameters in GOLD program for vanadium compounds and the validation of the method on five X-ray structures of V^IVO and V^V species bound to proteins; (2) the prediction of the binding site and enantiomeric preference of [VO­(pic)₂(H₂O)] to lysozyme, for which the X-ray diffraction analysis displays the interaction of a unique isomer (i.e., OC-6–23-Δ) through Asp52 residue, and the subsequent refinement of the results with quantum mechanics/molecular mechanics methods; (3) the application of the same approach to the interaction of [VO­(ma)₂(H₂O)] with lysozyme. The results show that convenient implementation of protein–ligand docking programs allows for satisfactorily reproducing X-ray structures of metal complexes that interact with only one coordination site with proteins and predicting with blind procedures relevant low-energy binding modes. The results also demonstrate that the combination of docking methods with spectroscopic data could represent a new tool to predict (metal complex)–protein interactions and have a general applicability in this field, including for paramagnetic species