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Print version ISSN 0103-5053
On-line version ISSN 1678-4790
J. Braz. Chem. Soc. vol.17 no.8 São Paulo Nov./Dec. 2006
IDepartamento de Química, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis - SC, Brazil
IIInstituto de Química, Universidade Federal do Rio de Janeiro 21945-970, Rio de Janeiro - RJ, Brazil
IIIInstituto de Física, Universidade Federal de Goiás, 74001-970 Goiânia - GO, Brazil
IVDepartamento de Química, Universidade Federal do Paraná, 81531-970 Curitiba - PR, Brazil
The reaction of Fe(ClO4)3.nH2O with N,N'-bis[(2-hydroxybenzyl)-N,N' -bis(1-methylimidazole-2-yl-methyl)]ethylenediamine (H2bbimen) affords two geometric isomers, A and B, of the complex cation [Fe(bbimen)]+, which were fully characterized by IR and UV-visible spectroscopies, ESI mass spectrometry, molar conductivity measurements, cyclic voltammetry, spectroelectrochemistry and EPR spectroscopy. The geometry of one of these isomers has been clearly demonstrated through X-ray crystallographic analysis. It crystallizes in the monoclinic system, space group P21/c, a = 14.104 (3), b = 15.626 (3), c = 13.291 (3) Å, b = 98.07 (3)º, Z = 4, R1 = 6.35% and wR2 = 20.57%. The electrochemical properties of [Fe(bbimen)]+ (-0.58 V versus NHE) are quite similar to those of transferrins (-0.52 V versus NHE) and indicate that it is a good model for the redox potential of these metalloenzymes. EPR spectroscopy was the only spectroscopic technique able to differentiate the isolated isomers A and B. EPR studies revealed that isomer A is better described as a rhombically distorted (E/D @ 0.33) high-spin FeIII complex (g1 @ 4.1 with a shoulder at g2 @ 9.0), while the spectrum of B has a set of lines at g1 @ 3.0, g2 @ 3.6 and g3 @ 5.1, in addition to the line at g1 @ 4.2 and a shoulder at g2 @ 9.0, which have been ascribed to FeIII complexes in axial symmetry (E/D @ 0.22). Semi-empirical theoretical studies, combined with EPR data, were essential to the proposition of the geometric structures of A and B.
Keywords: FeIII complex, geometric isomers, EPR, transferrins, semi-empirical studies
A reação entre Fe(ClO4)3.nH2O e N,N'-bis[(2-hidroxibenzil)-N,N' -bis(1-metilimidazol-2-il-metil)]etilenodiamina (H2bbimen) resulta na formação de dois isômeros geométricos, A e B, do cátion complexo [Fe(bbimen)]+, os quais foram isolados e caracterizados por espectroscopia na região do infravermelho e UV-visível, espectrometria de massas, medidas de condutividade molar, voltametria cíclica, espectroeletroquímica e espectroscopia de ressonância paramagnética eletrônica (RPE). A geometria de um desses isômeros foi claramente demonstrada por análise cristalográfica de raios X de monocristal. O composto cristaliza no sistema monoclínico, grupo espacial P21/c, a = 14,104 (3), b = 15,626 (3), c = 13,291 (3) Å, b = 98,07 (3)º, Z = 4, R1 = 6,35% e wR2 = 20,57%. As propriedades eletroquímicas do cátion [Fe(bbimen)]+ (-0,58 V versus NHE) são bastante similares às das transferrinas (-0,52 V versus NHE), indicando que o complexo é um bom modelo para as propriedades redox daquelas metaloenzimas. A espectroscopia de RPE foi a única técnica espectroscópica capaz de diferenciar os dois isômeros isolados (A e B). Os estudos de RPE revelaram que o isômero A trata-se de um complexo de FeIII spin alto distorcido rombicamente (E/D @ 0,33) e apresenta um espectro caracterizado por uma linha estreita em g1 @ 4,1 e outra larga em g2 @ 9,0. O espectro de RPE do isômero B apresenta, além das linhas em g1 @ 4,2 e em g2 @ 9,0, um conjunto de linhas em g1 @ 3,0, g2 @ 3,6 e g3 @ 5,1, que têm sido atribuídas a complexos de FeIII com simetria tendendo à axial (E/D @ 0,22). Estudos teóricos empregando cálculos semi-empíricos, combinados com os dados de RPE, foram essenciais para a atribuição das estruturas geométricas dos isômeros A e B.
Transferrins (Tfs), or siderophilins, are a family of Fe-binding proteins belonging to the Fe-tyrosinate class. In vertebrates, they are found in blood (serum transferrin), eggs (ovotransferrin) and milk (lactoferrin). The main physiological role of serum transferrin is the Fe transport through the circulating blood and its release to the Fe-dependent cells. Another role is believed to be played by ovotransferrin and lactoferrin, which involves bacteriostatic effects.1,2 As the serum concentration of transferrin is about 35 µmol L-1, and about 70% of it is in the apo-form (protein depleted of Fe), it is also proposed to be a blood transportmer of several other metal ions, including vanadium, aluminum, gallium and cobalt.3 Of the Fe-dependent cells, tumor cells are probably the ones of most concern because of their high demand for iron and as a consequence they exhibit enhanced transferrin receptor (TfR) expression.4
During the lifetime of serum transferrin in the circulation system, it is able to perform reverse uptake and deliver Fe about 100-200 times, and thus an understanding of the kinetics and the mechanism involved in the fundamental physiological process is of interest.5 It has been proposed that the first step is the coordination of FeIII to transferrin, which is coupled to the synergistic binding of a carbonate ion. The FeIII-Tf complex is then transported through the blood to the Fe-dependent cells, where the FeIII-Tf complex binds to a membrane transferrin receptor. This system is then internalized by the cell to an ATP-driven proton-pumping endosome (pH 5.4-6.0), where the metal is released as FeII. This then leaves the endosome via a membrane metal ion transporter (DMT).6
In order to better understand this process, the full characterization of transferrins is of fundamental importance. The structures of human lactoferrin,7 serum transferrin,8,9 and duck ovotransferrin10 have all been well studied using X-ray crystallography and are quite similar. They are bilobal proteins with each domain (C- and N-lobes) binding one FeIII ion. As the FeIII uptake is carbonate-dependent, its coordination sphere is composed of the two oxygen atoms of this "synergistic" ion, two phenolate oxygen atoms from tyrosine residues, one imidazole nitrogen atom from histidine and one carboxylate oxygen from aspartic acid (Figure 1).7-10
In addition to the structural characterization, transferrins have also been investigated using other techniques. Human lactoferrin gives an electronic spectrum characterized by two ligand-to-metal charge transfer (LMCT) bands at 465 nm and 280 nm, both ascribed to tyrosinate ®FeIII charge transfer transitions.11 Mössbauer spectra of human lactoferrin and serum transferrin display isomer shifts of 0.39 mm s-1 and 0.38 mm s-1 respectively, which are typical of high-spin FeIII centers.12 Additionally, the serum transferrin spectrum shows a large quadrupole splitting reflecting the non-symmetrical coordination field around the FeIII ion, as shown by the structural analysis.8,11 In agreement with the Mössbauer data, the EPR spectrum of serum transferrin displays a sharp signal at g @ 4.3 and a shoulder at g @ 9.0, both characteristics of high-spin FeIII ions.12
As the iron transport involves the uptake of FeIII and the release of FeII ions, knowledge of the redox potentials of Fe-bonded transferrins is extremely important. Redox potentials of human serum transferrin have been investigated under physiological (7.4) and endosomal (5.8) pH conditions. Spectroelectrochemical measurements13 revealed that E1/2 = -0.52 (8) V versus NHE at pH 7.4. At pH 5.8, the redox potentials (E1/2) of the three possible FeIII-Tf forms were measured: the diferric (E1/2 = -0.526 V versus NHE), the monoferric C-lobe (E1/2 = -0.501 V versus NHE) and the monoferric N-lobe (E1/2 = -0.520 V versus NHE) forms.14 All of these measured redox potentials are too low for reduction of FeIII by physiological agents. However, it has recently been demonstrated that the interaction of the FeIII-Tf complex with the membrane transferrin receptor (TfR) raises the potential by more than 200 mV, explaining the FeIII®FeII reduction in physiological medium.6
Based on these studies, several articles have been published reporting FeIII complexes with phenolate- and pyridine/imidazole-containing ligands as models for Fe-tyrosinate proteins.15-20 Very recently, we reported16 the synthesis and full characterization of a series of FeIII complexes, [Fe(bbpen-X)]+, using hexadentate ligands (H2bbpen-X) containing pyridine and phenol pendant arms. In this paper, we show that the reaction of the analogous H2bbimen (Scheme 1) with Fe(ClO4)3.nH2O affords a mixture of geometric isomers (A and B), which were only differentiated by EPR analysis. In order to determine the structure of the FeIII complexes, semi-empirical studies were a helpful tool when combined with EPR spectroscopic data.
H2bbpen, N,N'-bis-(2-hydroxybeE, normal hydrogen electrode.
Electrochemical and spectroscopic data were collected in high purity solvents, and high purity argon was used when necessary to obtain inert atmosphere. All other chemicals and solvents were of reagent grade, purchased from commercial sources, and used without further purification.
Physical measurementsnzyl)-N,N'-bis-(2-pyridin-2-yl -methyl)ethylenediamine; H2bbimen, N,N'-bis-(2-hydroxybenzyl)-N,N'-bis-(1-methylimidazole-2-yl-methyl) ethylenediamine; TBAPF6, tetra-n-butylamonium hexafluorophosphate; ESI-MS, electrospray ionization mass spectrometry; CV, cyclic voltammetry; IR, infrared spectroscopy; EPR, electron paramagnetic resonance spectroscopy; SCE, standard calomel electrode; Fc, ferrocene; Fc+, ferrocenium ion; NH
Infrared spectra were obtained on a FT-IR Perkin-Elmer 16PC spectrophotometer as KBr pellets or films. Elemental analyses were performed on a CHN Perkin-Elmer 2400 analyser. Molar conductivity was measured in CH3CN (10-3 mol L-1) at 298K with a Digimed CD-21 equipament. Electrospray-ionization (ESI-MS) mass spectra were recorded in acetonitrile using a Micromass LCT time-of-flight mass spectrometer with electrospray and APCI, coupled to a Waters 1525 Binary HPLC pump. UV-visible absorption spectra were measured in CH3CN on a Perkin-Elmer Lambda 19 spectrophotometer. Cyclic voltammograms were recorded at room temperature using a PAR 273 (Princeton Applied Research) potentiostat in acetonitrile solution, under argon atmosphere, with TBAPF6 (0.1 mol L-1) as supporting electrolyte. A standard three-electrode cell was used: a gold working electrode, a platinum wire auxiliary electrode and a SCE reference electrode. Ferrocene was used as internal standard (E1/2 = 0.16 V versus SCE).22 Spectroelectrochemical experiments were carried out at room temperature in acetonitrile, under argon, with TBAPF6 (0.1 mol L-1) as supporting electrolyte, using an optically transparent thin-layer cell constructed according a previously reported procedure.23 A gold minigrid and a platinum wire were used, respectively, as working and auxiliary electrodes, and a SCE was used as the reference electrode. Potentials were applied with a PAR 263 potentiostat/galvanostat and the spectra were recorded with a Perkin-Elmer Lambda 19 spectrophotometer. Spectral changes were registered after the establishment of equilibrium (120 s) and the experiment was stopped when no further changes were observed. Potentials were applied in the range of -0.84 to -1.06 V versus Fc+/Fc and the spectra recorded from 300 to 750 nm. The Fc+/Fc couple was used separately to monitor22 the reference electrode (E1/2 = 0.16 V versus SCE). X-band EPR spectra were recorded on a Bruker ESP 300E spectrometer at 77 K in CH2Cl2 solution.
Synthesis of [Fe(bbimen)]ClO4
Mixture of isomers (1). Fe(ClO4)3.nH2O (0.36 g, 1 mmol) was slowly added to a methanolic solution of H2bbimen (0.46 g, 1 mmol, 30 mL). This reaction mixture was heated (~ 40 0C) under stirring for ca. 30 min. After cooling the solution to room temperature, a violet microcrystalline precipitate was filtered off, washed with small amounts of cold 2-propanol and dried under vaccum. Yield 0.40 g (62%). FT-IR (KBr pellet) nmax/cm-1: n(O-H) 3426; n(C=Nimidazole) 1592; n(C=C) 1514-1446; n(C-Ophenol) 1278; n(Cl-O) 1154 and 1094. ESI-MS m/z (positive mode): 512.2 (6.38%), 513.2 (2.25%), 514.2 (100%), 515.2 (32.63%) and 516.2 (5.88%). Anal. Calc. for FeC28H38 N6O8Cl: C, 49.61; H, 5.65; N, 12.40. Found: C, 49.62; H, 5.11; N, 12.64%. Molar conductivity: 130 W-1 cm2 mol-1 in acetonitrile at 298 K (1:1 electrolyte).24 Few single crystals suitable for X-ray crystallographic analyses were obtained by slow evaporation of a solution of 1 in methanol:ethanol:water (10:1:1).
While attempting to find solvent systems to recrystallize the product, we were able to isolate two geometric isomers of [Fe(bbimen)]ClO4 by fractional crystallization. About 60% of the mixture of isomers (1) is soluble in hot acetone (isomer A) and was recrystallized in this solvent, yielding sharp purple needles that were not suitable for X-ray analysis. The remaining amount (isomer B) was then recrystallized in methanol yielding a microcrystalline sample.
Isomer A. ESI-MS m/z (positive mode): 512.2 (6.41%), 513.2 (2.25%), 514.2 (100%), 515.2 (32.73%) and 516.2 (5.89%).
Isomer B. ESI-MS m/z (positive mode): 512.2 (6.16%), 513.2 (2.26%), 514.2 (100%), 515.2 (32.49%) and 516.2 (5.87%).
Caution! Perchlorate salts of metal complexes with organic ligands are potentially explosive, and only small amounts should be carefully handled.
A violet crystal was selected and isolated for crystallographic analysis with a CAD-4 diffractometer. Cell parameters were determined from 25 carefully centered reflections in the q range 8.79-15.25º using a standard procedure.25 Data were corrected for Lorentz and polarization effects26 and for absorption27 (transmission factors 0.7305 and 0.9546). The structure was solved with SIR9728 and refined by full-matrix least-square methods using SHELXL97.29 The disorder in the perchlorate ion was modeled with two alternative positions for each oxygen atom. At C7, C8 and C2E, the H atoms were also placed using a standard disordered model. All non-H atoms were refined with anisotropic displacement parameters, except for O22. Hydrogen atoms were added at calculated positions and included in the structure factor calculations, with C-H = 0.93 Å (0.96 Å for methyl groups) and Uiso(H) = 1.2Ueq(C) or 1.5Ueq (methyl C). Other selected crystallographic information is shown in Table 1.
All geometry optimizations were performed using semi-empirical PM3TM molecular orbital calculation using the Spartan 04 program.33 Theoretical vibrational frequencies were used to find the minimum geometries. This method has been successfully used in cases involving transition metal complexes.30-32 The spin state of the FeIII isomers was stated as high-spin, ground state 6S, according to the EPR data. The calculations were carried out on a 2.6 GHz Athlon PC, with 1 GB RAM and 40 Gb HD, under the Windows 2000 operational system.
Results and Discussion
H2bbimen was prepared in good yield as previously described.21 It reacts with Fe(ClO4)3.nH2O in methanol to give a mixture (1) of geometric isomers (A and B) of the stable cation complex [Fe(bbimen)]+. The mixture was separated by fractional crystallization in hot acetone.
X-ray structural characterization
A single crystal suitable for X-ray analysis was isolated from 1, i.e., from the mixture of isomers. The structure of the complex consists of a discrete mononuclear cation, [Fe(bbimen)]+, and a ClO4 counterion, in general positions. The elemental cell also possesses an ethanol molecule as crystallization solvent. Crystallographic data and main bond distances and angles are presented in Tables 1 and 2, respectively. X-ray crystallographic analysis shows that the FeIII center is in a pseudo-octahedral environment, with the two halves of the bbimen2 ligand coordinated in a facial mode (Figure 2). This same arrangement (fac-N2O) is observed in other complexes with the analogous hexadentate bbpen2 ligand: [FeIII(bbpen)]+,16,20 [VIII(bbpen)]+,34 and [MnIII(bbpen)]+.23 The equatorial plane is geometrically defined by the O1-O2-N1-N2 atoms, from which the FeIII deviates only 0.001 Å. The equatorial plane is then composed of two nitrogen and two oxygen atoms from the ethylenediamine backbone and the phenolate groups, respectively. They are coordinated in such a way that the nitrogen atoms are cis to each other, and trans to the oxygen atoms. Completing the coordination sphere of the metal center are the two nitrogen atoms from the 1-methylimidazole group. The octahedral geometric distortion can be observed by the angles of the FeIII coordination sphere that deviate from 90°(Table 2). The coordination of the ethylenediamine group results in a distorted five-membered ring (FeN2C5C6N1), in which the C5 and C6 atoms lie at opposite sides of the equatorial plane, with deviations of - 0.358 and 0.202 Å, respectively.
The coordination of the phenolate groups in the equatorial plane has been observed in several other FeIII complexes: [Fe(bbpen)]+,16,20 [Fe(ehpg)],36 [Fe(hbed)],36 [Fe(ehgs) (CH3OH)],37 [Fe(salen)(Im)2],38 [Fe(sal2trien)]+,39 [Fe(salen) (4-mim)2]+,38 and [Fe(salen)(1-mim)Cl].38 The Fe-Oph average bond distance (1.884 Å) is very similar to that reported for [Fe(bbpen)]+ (1.87 Å). Also, these distances are the shortest of the coordination sphere and, as a consequence of the trans influence, make the Fe-Nam the longest ones (av. 2.270 Å). A comparison of the average Fe-N bond distances in the axial positions shows a decrease from 2.15 Å in [Fe(bbpen)]+ to 2.115 Å in [Fe(bbimen)]+, as a consequence of the greater basicity of the imidazole groups. A comparison of the FeIII-OTyr and FeIII-NHis bond distances reported11 for human lactoferrin (Fe-O435: 1.92 Å and Fe-N597: 2.13 Å) and those presented here for 1 (Fe-O1: 1.877 (5) Å and Fe-N31: 2.269 (5) Å) shows a good agreement. This indicates that using phenol and 1-methylimidazole groups as pendant arms in the design of ligands for model complexes, good structural approximations are obtained to mimic tyrosine and histidine amino acids.
IR spectroscopy and ESI-MS. The IR spectra of 1, A and B are quite similar and characterized by typical bands of the ligand skeletal, in addition to a band at 1094 cm-1 attributed to the ClO stretching of the perchlorate anion (Figure S1).40 A comparison with the IR spectrum of the free H2bbimen reveals a decrease in the band at 1372 cm-1, which indicates the coordination of the phenol group in its deprotonated form. The ESI-MS (positive mode) spectra of 1, A and B were recorded from freshly prepared solutions in acetonitrile (Figure S2). In fact, the spectra of A and B are identical, with the base peak (100%) corresponding to [Fe(bbimen)]+ at m/z+ 514.2. The other four observed peaks agree quite well with the predicted isotopic distribution for a Fe center (predicted: 514.18 (100%); 515.18 (33.1%); 512.18 (6.4%); 516.18 (5.9%) and 513.19 (1.8%)). The molar conductivities of 1, A and B in acetonitrile at 298 K are all around 130 W-1 cm2 mol-1 , which agrees with 1:1 electrolyte solutions.24 Therefore, we conclude that the first coordination sphere of the FeIII center is maintained intact when the complex is dissolved in acetonitrile.
UV-visible spectra. The UV-Visible spectra of 1, A and B were recorded in acetonitrile and show the same behavior with bands at identical wavelengths. The spectrum of 1 (Figure 3) is characterized by transitions at lmax/nm (e/mol L-1 cm-1): 236 (13500-shoulder); 278 (11300); 321 (7700) and 542 (4700). As the H2bbimen spectrum (Figure 3-inset) has bands at lmax/nm (e/mol L-1 cm-1): 213 (29000) and 276 (6100), the two bands observed for 1 at higher energy are attributed to p ® p* internal transitions of the aromatic rings. The bands at lower energy (321 and 542 nm) can be ascribed to LMCT transitions from the pp orbital on the phenolate oxygen to the half-filled dp* (t2g) and ds* (eg) on FeIII.11,15-20,41 Comparing the UV-Visible data of 1 with those reported16,20 for the analogous [Fe(bbpen)]+, it is observed that there is a hypsochromic shift of the pp ® dp* LMCT band from 574 to 542 nm when pyridine groups in H2bbpen are replaced by 1-methylimidazole groups in H2bbimen. These results are interpreted as a consequence of the greater basicity of the 1-methylimidazole groups (pKa1 @ 2.06)42 compared to the pyridine groups (pKa1 < 1.3).43 This effect has also been observed in several other complexes with the same number of phenolate groups and a variety of other pendant arms with different Lewis basicity.17-19,41
The electronic spectrum of 1 was also recorded in the solid state (KBr pellets, diffuse reflectance) and revealed the same behavior observed in acetonitrile (lmax at 538 and 318 nm), indicating no changes in the coordination sphere of 1 when in solution, in agreement with the ESI-MS mass spectral data.
Electrochemistry and spectroelectrochemistry. The redox behavior of 1, A and B was investigated by cyclic voltammetry and, as observed using all other techniques discussed above, it is quite similar. Complexes A and B have one reversible one-electron redox couple at approximately -0.58 V versus NHE (-0.98 V versus Fc+/Fc) ascribed to the FeIII ® FeII redox process (Figures 4 and S4). This value is cathodically shifted (-0.16 V versus NHE) when compared to that of [Fe(bbpen)]+ (-0.42 V versus NHE),16 reflecting the decrease in the Lewis acidity on the FeIII center resulting from the ligand basicity increase.17,18 Regarding the electrochemical properties of transferrins, the redox potential of -0.52 V versus NHE is in close proximity to that observed for [Fe(bbimen)]+ (-0.58 V versus NHE), which indicates that it is a good model for the redox potential of transferrins.
In order to investigate the spectral changes during the FeIII ® FeII redox process, spectroelectrochemical measurements were carried out under the same experimental conditions as those employed in the CV studies. A decrease in the LMCT phenolate ® FeIII band at 542 nm, with a simultaneous increase in a new band at 420 nm was observed (Figure 5). This band (420 nm) is tentatively attributed to an FeII ® 1-methylimidazole MLCT transition. This kind of transition has been observed in other systems employing pyridine and pyrimidine groups as ligands, and corroborates this assignment.16,44 During the whole process an isosbestic point was clearly observed at 340 nm. The presence of isosbestic points provides strong evidence for only two species present in solution during the redox process. Figure 5 also presents the Nernst plot, which is in agreement with the cyclic voltammetric data, and provides a redox potential of -0.94 V versus Fc+/Fc for the transference of one electron in the process.
Proposed geometric isomers for A and B
Since EPR is very sensitive to small distortions in the coordination sphere of the metal center, it was the only spectroscopic technique able to distinguish between the two isolated geometric isomers (A and B) of [Fe(bbimen)]+. X-band EPR spectra were recorded from frozen solutions of 1, A and B in CH2Cl2 at liquid nitrogen temperature, and are shown in Figure 6.
The spectrum of 1 exhibits a sharp signal at g1 @ 4.3, a shoulder at g2 @ 9.2 and another g set of absorption lines at g1' @ 3.7, g2' @ 4.0 and g3' @ 5.2. It is best described as a combination of the A and B spectra. The spectrum of A presents the sharp signal at g1 @ 4.1 and a shoulder at g2 @ 9.1, as expected for the middle and lower Kramer's doublet transitions of a rhombically distorted high-spin FeIII complex (E/D @ 0.33), ground state 6S.45,46 The spectrum of B, in addition to the peak at g1 @ 4.2 and the shoulder at g2 @ 9.0, also shows a set of peaks at g1' @ 3.0, g2' @ 3.6 and g3' @ 5.1, which has been assigned to weak resonances of the ground Kramer's doublets in an axial symmetry (E/D @ 0.22).11,17,47,48
The same behavior has been observed for other octahedral FeIII complexes18 and for transferrins.11 In transferrins this may be due to the slight distortions in the FeIII coordination spheres of the N- and C-lobes. Considering the similarities in the EPR spectra of transferrins and [Fe(bbimen)]+, one would conclude that the complex represents a good model for the EPR properties of these metalloenzymes.
The coordination of bbimen2 to FeIII could theoretically afford the three geometric isomers represented in Figure 7. As shown in our previous discussion, the geometry of one of these structures has been clearly demonstrated through the X-ray crystallographic analysis, while distinct EPR properties were found for the other isolated isomers.
Aiming to investigate the formation of these possible geometric isomers, semi-empirical studies were performed. These studies revealed that only two of the three structures (Figure 7) were confirmed as being true minimals. This was inferred by means of the vibrational frequency calculations, that showed all frequencies to be real. Calculated energies of the two optimized configurations show that (1) is favored by ca. 12 kcal mol-1 in relation to (2), and in spite of a relative energy difference, the results are in good agreement with the trends observed experimentally. It is also observed that only configuration (1) shows a rhombic behavior, which is in agreement with the structure shown by X-ray analysis (Figure 2), and gives a theoretical vibrational spectrum in good agreement with the experimental data (Figure S2). As the EPR studies revealed that isomer A has rhombic symmetry, it seems reasonable to assign it as being configuration (1). On the other hand, the geometry of isomer B can be assigned to configuration (2) (Figure 7). The graphical representation of the SOMO molecular orbitals for the geometric isomers A and B (Figure 8) shows that both have the main contribution of the pp orbital from the phenolate groups, which corroborates the fact that similar results were observed in the UV-Visible data. As the electronic transitions (321 and 542 nm) have been assigned to LMCT transitions from the pp orbital on the phenolate oxygen to the half-filled dp* (t2g) and ds* (eg) on FeIII,11,15-20,41 and both isomers A and B have the SOMO orbital with the same participation of the phenolate groups, the two complexes should have similar electronic spectra. Therefore, we have demonstrated here that the theoretical calculations describe the electronic behavior of both isomers, and are in good agreement with the experimental data.
In spite of different calculation methods being used to obtain the data presented here for [Fe(bbimen)]+ and those reported16 for [Fe(bbbpen)]+, a comparison between these results showed that, in both complexes, the SOMO participation is predominantly from the phenolate groups. In addition, the LUMO of [Fe(bbbpen)]+ and [Fe(bbimen)]+ are mainly of the pyridine and the imidazole groups, respectively.
In summary, we have synthesized, isolated and characterized two geometric FeIII isomers employing the ligand H2bbimen. We have demonstrated that the substitution of the two pyridines in H2bbpen by two 1-methylimidazole groups in H2bbimen was successful for tuning the redox properties of [Fe(bbimen)]+, making it a good model for the redox properties of transferrins. In addition, we established that EPR was the only spectroscopic technique able to differentiate the isolated isomers A and B, and, when combined with semi-empirical calculations, was essential to describe their structures. It was also possible to demonstrate that the main contributions for the SOMO and the LUMO are from the phenolate and the imidazole groups, respectively, as previously observed for the analogous [Fe(bbpen)]+.
Crystallographic data (atomic coordinates, equivalent isotropic displacement parameters, calculated hydrogen atom parameters, anisotropic thermal parameters and bond lengths and angles) have been deposited at the Cambridge Crystallographic Data Center (deposition number CCDC 609269). Copies of this information may be obtained free of charge from: CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: +44-1223-336-033; e-mail: email@example.com or http://www.ccdc.cam.ac.uk). Additional Figures are also available at http://jbcs.sbq.or.br, as PDF files.
The authors are grateful for grants provided by PRONEX, CAPES, PADCT, FINEP, CNPq and Fundação José Pelúcio Ferreira to support this research. The authors also would like to acknowledge Prof. Vincent L. Pecoraro (University of Michigan, USA) for the mass spectra and the elemental analysis.
To Luiz Sérgio Gonçalves da Cunha (in memoriam). To Arlindo Scarpellini (in memoriam).
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Received: June 11, 2006
Published on the web: December 1, 2006