Pergamon

Polyhedron Vol. 16, No. 5, pp. 789-794, 1997 Copyright 0 1996 Elsevier Science Ltd

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Synthesis and characterization of 3-hydroxy-4- pyridinone-oxovanadium(IV) complexes

John Burgesqa Baltazar De Castro,b Celeste Oliveira,” Maria Rangel”* and Walkiria Schlindweind

“Department of Chemistry, University of Leicester, Leicester LEl 7RH, U.K.

bDepartamento de Quimica, Faculdade de Ci&ncias do Porto, 4050 Porto, Portugal

‘Institute de CGncias Biomtdicas de Abel Salazar, 4050 Porto, Portugal

dChemistry Department, De Montfort University, Leicester LEl 9BH, U.K.

(Received 28 June 1996; accepted 12 July 1996)

Abstract-The synthesis and characterization of several new bis-ligand-oxo-vanadium(IV) complexes con- taining 1,2-substituted-3-hydroxy-4-pyridinonates or ethylmaltolate (3-hydroxy-2-ethyl-pyranonate) are reported. Structures are proposed based on EXAFS data. Copyright 0 1996 Elsevier Science Ltd

Keywords: vanadium(N) complexes ; pyranonate and pyridinonate complexes ; EXAFS ; UV-vis spectra.

Since the seventies, vanadium has been associated with insulin and its role in the body [l]. Control of glucose levels in plasma has been achieved, in vitro and in vivo, by means of vanadium administration in the form of inorganic salts [2]. However, as these compounds are poorly absorbed, the required high doses have been associated with undesirable side effects. In order to achieve better absorption and so reduce the doses of the element, it seemed appropriate to administer it in the form of an organic matrix. The synthesis of a potential insulin substitute, bis(mal- tolato)oxovanadium(IV) [VO(ma),, BMOV], was reported in 1992 by Orvig and co-workers [3] ; its structure and properties have since been fully docu- mented [4]. This compound was administered to dia- betic rats and the studies demonstrated that BMOV is effective, at a lower dose than inorganic vanadium salts, in regulating glucose levels in the plasma [S]. It lowered cholesterol and triglyceride levels and ameli- orated the cardiac disfunction normally observed in diabetic patients [6]. It exhibited no significant toxic effects on hepatic and kidney functions [7].

*Author to whom correspondence should be addressed.

Malt01 (3-hydroxy-2-methyl+pyranone) (la) is a permitted food additive, used in the baking industry. It, or ethyl malt01 (lb), reacts with primary amines to yield 3-hydroxy-2-methyl(ethyl)-4-pyridinones (2a- b). This class of ligands has recognized phar- maceutical importance, in iron and aluminium oral chelation therapy [8] and in the administration of gallium and indium isotopes in radiodiagnosis and radiotherapy [9]. Pyridinone ligands are not only good chelators of M”’ and M” metal ions, but also permit modulation of the hydrophilic/lipophilic balance (HLB), of ligands and of complexes, by changing the substituent on the ring nitrogen atom. Such a possi- bility of tailoring the HLB is of paramount import- ance for substances to be used in vivo, as this parameter is crucial for the transport properties of ligands and complexes across biological membranes.

We now report the synthesis and characterization of oxovanadium(IV) (vanadyl) complexes VOL*, in which the ligands L are anions of the 3-hydroxy-4- pyranone (lb) and of the 3-hydroxy4pyridinones (2a-b) (Fig. 1) ; the synthesis and solution chemistry of the analogous complex of la have been described earlier [4]. The new complexes have been char- acterized by elemental analysis and mass spec- trometry, and structurally by vibrational, electronic

789

790 J. Burgess et al.

0 PYRONES

R OH

la Me Hma

lb Et Hetma

R PYRIDINONES

0 R R’

2a Me H Hmpp

OH 2b Me Me Hdmpp 2c Et Me Hempp 2d Me C,H, HPPP

R 2e Et C,H, Hepp

I 2f Me 4-MeC,H,, Hptp

R’ 2g Me 4+-C&&H, Hpbp 2b Me 4-(n-C,H,,)C,H, Hphp

Fig. 1. Formulae of, and abbreviations for, the pyranone and pyridinone ligands used in this investigation.

and electron spin resonance (ESR) spectroscopy, and by EXAFS.

EXPERIMENTAL

The oxovanadium(IV) complexes were synthesized by adding the stoichiometric amounts of vanadyl sul- fate and the pyranone or pyridinone ligand in water, adjusting the pH to 5, and refluxing the mixture for about 1 h. The blue-grey solids that formed were filtered while the solution was still warm, washed with cold water or, for complexes of the more hydrophobic ligands, with methanol-water, and dried over phos- phorus pentoxide. Elemental analyses were performed at the Microanalytical Laboratory of the University of Manchester ; thermogravimetric analysis was carried out on a TA3000 instrument; mass spectra were obtained on a Kratos Concept instrument (fast atom bombardment and electron impact modes).

Vibrational spectra were obtained in potassium bromide discs on a Mattson 5000 FTIR spectrometer. Reflectance electronic spectra were recorded in the range 300-1200 nm at room temperature on a Shi- madzu UV-3101PC spectrometer, using barium sul- fate as reference material. X-band ESR spectra were recorded in solution at room temperature and at 77 K on a Bruker ESP300E spectrometer using diphenyl- picrylhydrazyl as reference. The solutions for ESR were prepared under anaerobic conditions in 1 : 1 chloroforn-toluene mixtures.

EXAFS experiments were performed in the region of the vanadium K-edge using station 7.1 at the Synchrotron Radiation Source, Daresbury, U.K. The beam energy was 2 GeV and a typical average stored ring current was 150 mA in multibunch mode and

brilliance configuration. Data were acquired in the EXAFS transmission mode with argon-filled ion chambers using an Si( 111) monochromator with 50% harmonic rejection. The data analysis was performed using the Daresbury EXAFS suite of programs.

RESULTS AND DISCUSSION

In exploratory experiments, the compounds were prepared either by adjusting the pH of the solu- tion to 9, as described for the bis(maltolato) oxovanadium(IV) complex [3], or by adjusting the pH of the solution to 5, as described for other oxo- vanadium(IV) complexes with bidentate oxygen ligands [lo]. The latter conditions were chosen, as the resulting products gave better elemental analyses.

Mass spectra show the expected peaks for the com- plexes VOLZ and for fragments VOL and L. The results relating to the most intense peak, together with the results of elemental analyses (CHN), are shown in Table 1 for the 10 compounds prepared. It is clear that all compounds must contain five-coordinate vanadium except for complex 2a, in which a water molecule appears to be bound in the sixth coor- dination position (also see below, in the EXAFS sec- tion). Thermogravimetric analyses are consistent with 2a being a monohydrate ; the remaining complexes are anhydrous.

The IR spectra exhibit in the range 1600-1440 cm-’ a set of four bands characteristic of pyranones or pyridinones [ 111. Upon coordination, the band characteristic of the O-H stretching vibration is lost, as expected, but the band characteristic of the V=O vibration remains well defined and appears, for all the compounds, within the range 965-993 cm-’ (Table

3-Hydroxy-4-pyridinone-oxovanadium(IV) complexes

Table 1. Data for elemental analysis, mass spectra, vibrational and electronic spectra

791

Compound %C %H %N MS (MH+) v(,V=O) (cm-‘) kl, (m@

VO(ma),

VO(etma),

VO(mpp), * H,O

la

lb

2a

45.6 3.2 - 318 993 410 ; 534 ; 609 ; 703 (45.5) (3.2) 48.8 4.1 - 346 993 399;544;621;710

(48.7) (4.1) 43.5

(43.3) (t:) (E) 316 983 393 ; 532 ; 622 ; 660

VD(dmpp), 2b 49.1 4.7 8.2 344 (49.0) (4.7) (8.2)

VO(empp), 2e 51.2 5.3 7.5 372 (51.7) (5.4) (7.5)

VO(PPPL 2d 62.2 4.3 5.8 468 (61.7) (4.3) (6.0)

VD(eppp)z 2e 62.5 4.9 5.7 496 (63.0) (4.9) (5.7)

VO(ptPP)* 2f 64.1 4.9 5.7 496 (63.0) (4.9) (5.7)

VO(pbpp)z 2g 66.3 6.2 4.9 580 (66.3) (6.3) (4.8)

VO(pbpp), 2h 68.4 7.0 4.3 636 (68.0) (7.0) (4.4)

a See Fig. 1 for definitions of abbreviations used for ligands.

965 415;528;651;784

967 417 ; 529 ; 643 ; 773

986 412; 542; 624; 683

969 397; 537; 627; 725

979 406; 549; 634; 714

976 405;547;641;716

977 406; 550; 634; 716

l), thus confirming the stability of the +4 oxidation state in the solid state.

Comparison of solution and reflectance electronic spectra of several of our complexes persuaded us to concentrate on the latter. Figure 2 shows some typical reflectance spectra. The solution spectra suffered from the disadvantage that it often proved difficult or impossible to locate the weakest band in the visible region, and from the complication of the introduction of solvation effects at too early a stage in the inves- tigation. Reflectance electronic spectra exhibit for all compounds four bands in the visible region, which appear in the following ranges: 393-417, 528-549, 609-651 and 70&784 nm. Spectra of la, 2c and 2f are shown in Fig. 2 ; the data for all compounds are summarized in Table 1. The optical spectra of vanadyl complexes are normally interpreted in terms of the energy level scheme derived originally by Ballhausen and Gray from a molecular orbital study for a square- pyramidal structure of C,,” symmetry [ 121, with the z- axis taken as the vanadium-oxygen double bond and the x- and y-axes along the equatorial bonds. In this scheme b2 MY) < e(L,&) < ML-y2) < aI (&), and three electronic transitions are predicted, and indeed normally observed, for vanadyl complexes. However, some complexes exhibit four bands, and it is then assumed that the ‘E(xy, yz) state is split in low symmetry. The three- or four-band patterns observed in optical spectra of vanadyl complexes and the assign- ment of the electronic transitions have been discussed and interpreted not only in terms of symmetry but also of stereochemistry and size of chelate ring [lo, 13-171. Furthermore, for vanadyl complexes for which c&tram isomerism is possible, and for which

the chelate rings are five-membered, the four-band pattern has been associated with the tram isomer, the three-band pattern with the ci.s. Using u-hydroxy- carboxylates as examples, the cis-tartrate exhibits three bands, the truns-tartrate four, with the same pattern for lactate, glycolate and diphenylglycolate complexes [10,18].

The bis(pyranonat0) and bis(pyridinonato) oxovanadium(IV) complexes described here have electronic spectra with four bands, and as the tran- sition energies are very similar to those reported for the a-hydroxycarboxylato complexes, the assign- ment developed for these latter complexes will be used: AEXY < BE,, < AEX~_Y2 < AE,z (or CT) [16]. This analogy can be extended further to postulate that our solid products consist of the tram isomer in each case. This is consistent with the recently reported crys- tal structure of VO(ma),, which shows the vanadium to be five-coordinate with distorted square-pyramidal geometry (the vanadium atom lies 0.07 A above the equatorial plane defined by the donor oxygen atoms) and the two maltolate ligands tram to each other [4]. Also, for VO(ma), the three low-energy bands appear at 534, 609 and 703 nm, in reasonable accordance with those reported in chloroform (where the authors implied four bands but quoted only three A,,, values, 549,602 and 752 nm) [lo]. These &, values are very different from those in strongly coordinating solvents such as pyridine (476, 610, 769 and 847 nm) [lo] or water (three bands only reported, at 441, 625 and 860 nm) [4].

For series of closely related ligands, as here, it is to be expected that differences in donor strength should arise from u donating power, and so the stretching

192 J. Burgess et al.

400 600 600

W-4 1200

Fig. 2. Diffuse reflectance spectra of the complexes VO(ma),, VO(empp), and VO(ptpp),.

frequency of the V=O bond can be a measure of its strength. A decrease in stretching frequency has been interpreted as resulting from an increase in electron donation to vanadium, thereby making it less able to accept charge from the oxygen, thus reducing the bond order. For the five-coordinate complexes [i.e. exclud- ing results for the hydrated complex, VO(mpp),H,O] values of v(V=O) correlate with expected stabilities, with the lowest value for the most strongly bonding ligand (2b) and the highest for the least strongly bond- ing (la). Furthermore, a reasonable linear correlation is observed between the energy (E cm-‘) of the (xy) + (z’) or (xy) + (x’-y’) transitions and v(V=O) for the five-coordinate bis(pyridinonato)oxovan- adium(IV) complexes.

ESR spectra were obtained, in chloroform-toluene solutions, at room temperature and at 77 K. At both temperatures they are well resolved and typical of a d’ electron configuration (S = l/2). At ambient tem- perature the isotropic spectra exhibit eight well- defined lines resulting from the hyperfine interaction of the unpaired electron with the vanadium nucleus (‘IV, Z = 7/2). The frozen solution spectra are similar for all the compounds, exhibiting strong anisotropy. It is possible to distinguish in the low-field and high- field regions lines representative of the parallel split- ting due to the hyperfine interaction of the unpaired electron with the vandium nucleus (“V, Z = 7/2) and a central region where different sets of lines cor- responding to the x and y components of the hyperfine interaction are superimposed. According to the optical spectra, and bearing in mind the low symmetry of our compounds, rhombic spectra are to be

* It may be noted that it took the authors of Ref. [4] several years and some good fortune to obtain an X-ray diffraction quality crystal of VO(ma),.

expected. Table 2 summarizes the values of gisO and Ai,,, obtained directly from the spectra at ambient temperature by averaging the separation of the -ml to +mZ transitions, as well as g,, and A,,, obtained directly from frozen solution spectra. The ESR par- ameters are practically invariant for all the com- pounds and are indicative of similar metal-ligand covalency.

In order to gain insight into the local structure of the synthesized complexes, EXAFS experiments were carried out, since it proved impossible to grow crystals of sufficient quality for single-crystal X-ray diffract- ometry.* The vanadium-oxygen bond distances obtained are given in Table 3, which also includes data for VO(ma), determined by X-ray diffraction for comparison. Both EXAFS and X-ray diffraction show two oxygen atoms at 3.7 8, from each vanadium, which are the nearest neighbours in adjacent layers. A detailed report and analysis of our EXAFS results will be published elsewhere [19]. The results confirm

Table 2. ESR parameters for the complexes in chloroforn- toluene solution at room temperature and at 77 K

Compound” Ligand 9.0 4.0

VOWa), la 1.98 92 VO(etma), lb 1.98 92 VO(dmpp), 2b 1.99 89 VO(empp), 2c 1.99 89 VwPPPh 2d 1.97 89 VWPPPh 2e 1.99 89 VwPtPP), 22 1.99 89 VWbPPh 2g 1.98 91 VWPhPPh 2h 1.99 89

911 “4

1.94 171 1.94 171 1.94 171 1.94 171 1.95 169 1.95 169 1.98 169 1.96 169 1.94 167

“See Fig. 1 for definitions of abbreviations used for ligands.

3-Hydroxy-4-pyridinone-oxovanadium(IV) complexes

Table 3. EXAFS results for the compounds studied

Nearest Number Distance neighbour of neighbour from

Complex” Ligand atom atoms vanadium (A)

VO(ma),b la 0 1 1.60 0 4 1.95

VO(mpp), * Hz0 2a 0 1 1.60 0 4 1.95 0 1 2.32

VO(dmpp), 2b 0 1 1.60 0 4 1.94

VO(PPP), 2d 0 1 1.59 0 4 1.94

VOWPP), 2f 0 1 1.61 0 4 1.94

VO@bpp), 2g 0 1 1.60 0 4 1.94

VO(phpp), 2b 0 1 1.61 0 4 1.94

a See Fig. 1 for definitions of abbreviations used for ligands. ‘X-ray diffraction data: V=O = 1.596 A; VO = 1.971, 1.998, 1.958, 2.204 A.

193

that all the compounds are five-coordinate, with the exception of 2a, for which a bound water molecule was detected at 2.3 A from the vanadium in the sixth coordination position. The other bond lengths are similar for all the compounds and are indicative of the presence of five oxygen atoms coordinated to the vanadium : the vanadyl-oxygen at 1.59-1.16 A, the four other oxygens at 1.941.95 A. These results are as expected, both in relation to the structure of VO(ma), and to the corresponding distances in VO(acac), and VO(bzac),, which, from single-crystal X-ray diffraction, are between 1.56 and 1.61 A and between 1.95 and 1.99 A, respectively [20].

The EXAFS results we have obtained for VO(ma), are in very good agreement with the X-ray diffraction data. We believe that the information obtained from the absorption technique is of great importance, as it permits the accurate establishment of structure in the vicinity of the metal in circumstances where single- crystal X-ray diffraction is not possible. In the present context, this means that we can obtain structural information on related complexes containing long hydrocarbon chain substituents in the pyridinone ligands, and on these complexes in solution; in other words, we shall be able to probe solvation of this group of complexes in a range of solvent media.

Table 3 indicates that the vanadium-oxygen bond lengths do not vary significantly between the various pyridinone complexes, thus showing that the local structure around the metal centre is not appreciably modified by changing the substituents on the ring nitrogen atom. This indicates that the HLB of these complexes can be tuned without altering the structure around the metal centre. Indeed, all our structural and

spectroscopic data suggest that inclusion of sub- stituents on the ring nitrogen does not significantly affect such properties of these complexes.

Acknowledgements-We are grateful to the JNICT and to the British Council for their support, and to Dr John Fawcett for structural calculations.

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