Synthesis of a New Phenolate-1-methylimidazole Hexadentate Ligand and the Crystal Structure of it ’ s First Vanadyl Complex

It is well established that vanadium plays an important role in many biological processes . In view of the recent reported binding of vanadium to tyrosinate residues in vanadium-modified transferrin , vanadium-phenolate chemistry is receiving a great deal of attention from the inorganic chemist . Despite the bindidng of iron(III)transferrin has been established through crystallographic studies (NO3 coordination and CO 32as synergistic anion), the coordination environment around the vanadium centre in vanadium-transferrins is not yet entirely known. It is well known that in the +3, +4, and +5 oxidation states, vanadium binds tighly to transferrin . In the +4 oxidation state, a vanadyl complex structure with octahedral geometry having an NO3 equatorial coordination (one tyrosinate, one aspartate, one histidine, and one monodentate carbonate) has been proposed recently for vanadium human lactoferrin, on the basis of computer simulations by using the atomic coordinates of the iron(III)and copper(II)-lactoferrin complexes . The coordination of histidine trans to the V=O bond has also been proposed . As a continuation of our work on the coordination chemistry of vanadium with biologically relevant ligands, we describe herein, the preparation and structural characterization of a VO 2+ complex, with a new N 4O2-donor ligand which contains the ethylenediamine backbone and two phenolate-type and two 1-methyl-imidazole-2-ylmethyl pendant arms. Interestingly, despite the numerous VO complexes with nitrogen and oxygen donor atoms described in the literature, 1 there are only very few examples of structurally characterized vanadyl(IV) complexes which contain phenolate and imidazole coordinated simultaneously to the metal center .


Introduction
It is well established that vanadium plays an important role in many biological processes 1 .In view of the recent reported binding of vanadium to tyrosinate residues in vanadium-modified transferrin 2 , vanadium-phenolate chemistry is receiving a great deal of attention from the inorganic chemist [3][4][5] .Despite the bindidng of iron(III)transferrin has been established through crystallographic studies (NO3 coordination and CO32-as synergistic anion) 6 , the coordination environment around the vanadium centre in vanadium-transferrins is not yet entirely known.It is well known that in the +3, +4, and +5 oxidation states, vanadium binds tighly to transferrin 7 .In the +4 oxidation state, a vanadyl complex structure with octahedral geometry having an NO3 equatorial coordination (one tyrosinate, one aspartate, one histidine, and one monodentate carbonate) has been proposed recently for vanadium human lactoferrin, on the basis of computer simulations by using the atomic coordinates of the iron(III)-and copper(II)-lactoferrin complexes 8 .The coordination of histidine trans to the V=O bond has also been proposed 8 .
As a continuation of our work on the coordination chemistry of vanadium with biologically relevant ligands 4,5 , we describe herein, the preparation and structural characterization of a VO 2+ complex, with a new N4O2-do-nor ligand which contains the ethylenediamine backbone and two phenolate-type and two 1-methyl-imidazole-2-ylmethyl pendant arms.Interestingly, despite the numerous VO 2+ complexes with nitrogen and oxygen donor atoms described in the literature, 1 there are only very few examples of structurally characterized vanadyl(IV) complexes which contain phenolate and imidazole coordinated simultaneously to the metal center 9 .

Syntheses
The ligand N,N'-bis(2-hydroxybenzyl)-N,N'-bis(1methylimidazole-2-yl-methyl)ethylenediamine (H2bbimen) was prepared in good yield by the condensation reaction of 1-methyl-2-imidazolecarboxaldehyde 10 and ethylenediamine and reduction with NaBH4, followed by alkylation of the diamine (bimen) with 2-bromo-methylphenyl acetate 11 , by the route in Scheme 1.The title complex was prepared as follows.A solution of VCl3 in dry acetonitrile was refluxed for 15 min under an argon atmosphere and equimolar quantities of H2bbimen and Et3N in tetrahydrofuran (thf) were added to the hot solution, followed by 30 min of reflux.After the addition of NaPF6 to the solution and cooling to room temperature under argon, a green precipitate of [V III (bbimen)][PF6] 1 was formed.This material is stable in the solid state, even in the presence of air, but oxidizes in acetonitrile solution under aerobic conditions.The lilac complex 2, [OV IV (Hbbimen)][PF6].2H2O, was obtained after leaving the green solution of 1 at room temperature over night, in the presence of air.Single crystals of 2 suitable for X-ray crystallography were obtained by recrystallization from a propan-2-ol-acetone-acetonitrile (1:1:1) solution of 2. The structure was solved by direct methods, full-matrix refinement on F 2 , anisotropic refinement for all non-H atoms of the complex molecule, isotropic refinement for water molecules and disordered PF6 group.The number of refined parameters was 390, R = 0.127 , wR = 0.273.

X-ray Crystallography
The quality of the refinement was limited by the intrinsic quality of the data and by the high thermal motion of the disordered PF6 group.All the H atoms were placed at geometrically calculated positions, except those of the water molecules that were not found.Crystallographic calculations were performed using the MOLEN, SHELXS86, SHELXL93 and ZORTEP computer program packages 12 .

Results and Discussion
The structure and atomic numbering scheme of 2 are shown in Fig. 1.The vanadium (IV) ion is in a pseudo-octahedral environment, in which one phenolate oxygen, one amine, and two 1-methylimidazole nitrogen atoms in trans positions, form the equatorial plane.The other amine nitrogen atom of the ethylenediamine backbone, in the trans position with respect to the terminal oxo group, completes the coordination sphere.It is important to note that, despite the similarities between the hexadentate H2bbimen and H2bbpen 5 ligands, [H2bbpen = N,N'-bis(2-hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)ethylenediamine], there are significant structural differences in their corresponding VO 2+ complexes.While in [OV IV (bbpen] 5 one pyridyl group of the ligand H2bbpen is pendant, in 2 one phenol group of H2bbimen is not coordinated to the vanadium (IV) center.This most probably arises due to distinct basicities of the coordinating pyridyl and 1-methylimidazole nitrogen atoms.As expected, the V-N(amine) of 2.36(1) Å trans to the V=O bond in 2, is 0.13 Å longer than the V-N(amine) bond in the equatorial plane and is a consequence of the strong trans influence of the oxo group.A similar trend in these bond lenghts has been observed in [OV IV (bbpen)], but with longer V-N(amine) bonds (0.05 and 0.03 Å for trans and cis to the oxo group, respectively) in complex 2. This fact can be associated with the higher rigidity of 2, due to the presence of three five-and one six-membered rings compared to [OV IV (bbpen)], which possesses two five-and two six-membered rings.In addition, the displacement of the V atom from the N3O plane (0.331 Å) for the present complex is smaller compared with that (0.345 Å) in [OV IV 9 .The V-N(1-methylimidazole) distances (av.2.08 Å) cis to the V=O bond, are similar to the V-N(imidazole) bond of 2.099 Å observed in the [OV IV (salimH)(acac)] complex 9 .