Stereospecific formation of vanadium mandelato complexes with [Fe(2,2′-bipyridine)3]2+ as a counter ion

Two vanadium complexes of mandelic acid having [Fe(bpy)3]2+ as counterion, [Fe(bpy)3][V2O4(rac-mand)2]·4.9H2O·0.1CH3CN (1, FeV2L2) and (H3O)[Fe(bpy)3]4[V3O7(S-mand)2]3·28H2O (2, FeV3L2) (bpy = 2,2’-bipyridine, mand2– = mandelato ligand, C8H6O32–) have been synthesized and characterized by single crystal X-ray diffraction and spectral methods. The FeSO4—bpy—KVO3—H2mand—H2O—CH3CN system exhibits a stereospecific behaviour: while from the system including racemic mandelic acid only the complex of the V2L2 type (1) could be obtained in crystalline form, the system with S-mandelic acid afforded the V3L2 (2) complex as the single crystalline product. All vanadium atoms exhibit tetragonal pyramidal coordination geometry with oxygen donor atoms of the oxido ligands and carboxylate anion. The stereospecific behaviour was investigated using the 51 V NMR spectroscopy, which revealed different composition of systems with racemic mandelic acid and S-mandelic acid after some preliminary period (≈ 15 days). The compound 2 is chiral non-racemic compound (space group P21212), the structure of which contains Δ-[Fe(bpy)3]2+ cations and [V3O7(S-mand)2]3– anions.


Introduction
Mandelic acid (Scheme 1) is a chiral alpha hydroxy carboxylic acid known for two hundred years [1].It exists in the form of two enantiomers and thus is a useful precursor for the synthesis of drugs [2,3], while the acid itself has significant antibacterial properties [4,5].Vanadium has already been known to be able to form some types of complexes in a stereospecific manner, focusing specifically to carboxylic acids, a stereospecific discrimination was observed for complexes employing tartrate [6], 2-amino-3-methylpentanoate (isoleucine) [7], and indeed mandelate [8].Whilst combining these two key parameters of mandelic acid and vanadium, in this work, we inspect the interaction of vanadium mandelato complexes with Δ-and Λ-[Fe(bpy) 3 ] 2+ .
Our previous investigations of vanadium(V) complexes incorporating mandelic acid established the existence of two types of solid vanadium mandelato complexes: [9,11].Actually, vanadium has been known for a long time to form complexes of the composition M 2 [V 2 O 4 (ligand) 2 ] (M 2 V 2 L 2 ) (ligand=alpha hydroxy monocarboxylic acid), however, the existence of a V 3 L 2 complex was proposed in the past only based on solution speciation studies [10], until the discussion about its possible existence was finally closed by an X-ray structure determination of (NH 4 ) 2.5 (NEt 4 )0.5[V 3 O 7 (R-mand) (S-mand)] in 2019 [11].Moreover, it was observed that the V 3 L 2 3− anion was only isolable in the presence of the racemic mandelic acid but not in an enantiopure environment.On the other hand, the system has shown a significant tendency towards a redox process (reduction of vanadium(V) with mandelic acid to vanadium(IV)) resulting in the impossibility to observe timelapse reactions in solutions.We have observed in this work that in the reaction system FeSO 4 -bpy-KVO 3 -mand-H 2 O-CH 3 CN there is no reduction of vanadium(V) and, advantageously, the presence of the chiral [Fe(bpy) 3 ] 2+ cation allows monitoring interactions between chiral ions.
In addition, heterometallic compounds often surmount homometallic compounds due to the presence of cooperative intermetallic effects [12,13].Vanadium heterometallic compounds, in particular, mediate in dinitrogen and nitric oxide activation [14], or exhibit significant antiproliferative and high cytotoxic activity [15,16]; giving the research presented herein a non-negligible application potential in bioinorganic chemistry.

Materials and methods
All chemicals were of analytical grade and were used as received.KVO 3 was prepared from purified NH 4 VO 3 as described previously [6].Elemental analyses C, H, N were determined on a Vario MIKRO cube (Elementar).The vanadium content was determined using an ICP MS Thermo Scientific iCap-Q; the iron content was determined using an AAS Perkin-Elmer Model 1100.Solid-state IR spectra were recorded on a Thermo Scientific Nicolet 6700 FTIR spectrometer in nujol mulls, KBr pellets and by employing the ATR technique.UV-vis spectra and CD spectra were recorded on a JASCO J-815 CD spectrometer in 1.0 cm quartz cuvettes at room temperature using water as solvent.

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Fe Mössbauer spectroscopy was performed using a Wissel spectrometer in transition arrangement at room temperature.α-Fe was used for calibration for fitting in the program NOR-MOS.The spectrum was recorded by the scintillation detector ND-220-M (NaI:Tl + ). 51V NMR spectra were recorded at 278 K on a VNMRS 600 MHz spectrometer (157.88MHz for 51 V) in 5 mm tubes.Chemical shifts (δ) are given in ppm relative to VOCl 3 as an external standard (δ = 0 ppm).
Data for X-ray single crystal diffraction were collected using a Bruker D8 VENTURE diffractometer (compound 1) and a Nonius KappaCCD diffractometer with Bruker APEXII detector (compound 2).The phase problem was solved by direct methods and structure model were refined using software SHELXT 2018/2 [17] and SHELXL 2018/3 [18].Geometric data were obtained using Platon [19].Graphics were obtained with Diamond [20].

X-ray diffraction
Crystal data, data collection and structure refinement details are summarized in Table 1.All non-hydrogen atoms were refined anisotropically.Hydrogen atoms were refined isotropically and were treated by a mixture of independent and constrained refinement.For compound 1, the solvent molecules CH 3 CN and H 2 O present in the structure acquired a mutually disordered arrangement and the solvent molecules were refined with their s.o.f.'s summing to unity.The solvent present in compound 2 could not be modelled with satisfactory results and its contribution to the diffraction data was subtracted by using the SQUEEZE procedure implemented in Platon.The selected bond parameters are listed in Table 2.
In the case that further precipitate is formed during the standing of preparative solutions for synthesis of 2, it is recommended to filtrate the solutions again.Nevertheless, by a longer standing of the solutions recrystallization of precipitate to crystalline product occurred (Figure S1, Supporting Information).

Synthesis
Upon at our numerous attempts at synthesizing vanadium mandelato complexes with [Fe(bpy) 3 ] 2+ as counterion, we observed some noteworthy phenomena: (a) Although the V 2 L 2 complex with (S)-mandelic acid exists in solution, we never obtained this complex in a pure crystalline form.In contrast, the V 2 L 2 complex with racemic mandelic acid easily provided crystals from solutions with n(V)/n(mand) ≥ 2 (compound 1).(b) Exactly opposite is the situation with the V 3 L 2 complex.
The crystals of the FeV 3 L 2 complex can be readily prepared under proper conditions using (S)-mandelic acid (compound 2), but we never succeeded in synthesising the FeV 3 L 2 complex using racemic mandelic acid (Scheme 2).(c) There is a distinct dependence of the reaction products on the mixed solvent CH 3 CN-H 2 O composition

NMR spectra
The 51 V NMR spectrum of a solution, whose composition corresponds to the conditions of synthesis of 2 is shown in Fig. 1.The spectrum is in principle identical with the spectrum of aqueous solution, upon considering shifts caused by changing the solvents [11].Besides the signals of vanadates [21][22][23], the spectrum exhibits the dominant signal of V 2 L 2 (−525 ppm) and the weak signal of V 3 L 2 (one V atom: the central vanadium atom V1 in Fig. 1).The signal of V 3 L 2 (two V atoms: the two equivalent vanadium atoms V2, V2' in Fig. 1) is overlapped by the strong signal of V 2 L 2 and can be seen as an upfield shoulder.The only difference in comparison with the spectrum of aqueous solution is that the V 3 L 2 (2 V) signal in water is seen as downfield shoulder of the dominant signal.
The comparison of the time dependence of the 51 V NMR spectra for systems with (S)-mandelic acid and racemic mandelic acid is shown in Fig. 2.These solutions were standing in beakers and were covered with Petri dishes at 5 °C.The solutions had the same composition, except the isomeric composition of mandelic acid.While standing, some products (precipitates) were formed (vide ultra).Roughly until the 15th day of standing, the spectra were very much alike, and the obtained solid products exhibited very similar IR spectra both for (S)-mandelic and rac-mandelic acid.After this period, a relatively fast differentiation of the 51 V NMR spectra has begun.The spectra of solutions containing (S)-mandelic acid exhibited strong peaks corresponding to V 2 L 2 + V 3 L 2 (2 V) and medium peaks of V 3 L 2 (1 V).
It must be noted that under conditions of the experiment, nearly all CH 3 CN was evaporated from the solution, what is documented also by the position of the V 2 L 2 + V 3 L 2 (2 V) peak (−532 ppm) that corresponds to the value for aqueous solution.In contrast to the spectrum of the system with (S)-mandelic acid, the spectrum of the solution with racmandelic acid after 35 days of standing exhibited only very a weak signal of V 2 L 2 + V 3 L 2 (2 V), while the V 3 L 2 (1 V) signal was completely absent.The 51 V NMR spectra are fully in accordance with the results of syntheses.After the preliminary period (approximately 0-15 days) and eventual filtration of the subsequent precipitate, 2 (FeV 3 L 2 ) was crystallizing.From the solutions with rac-mandelic acid, 1 (FeV 2 L 2 ) was crystallizing after the preliminary period.The synthesis of this compound is not dependent on the conditions of preparation and can be obtained for various V(CH 3 CN)/V(H 2 O) ratios and for n(V)/n(mand) between 2/2 and 3.35/2.The complicated course of the reactions preceding preparations of 1 and 2, which are moreover accompanied by the changes in composition of solvents (the preferential evaporation of acetonitrile) and in the concentrations of reacting ions due to the formation of precipitate, we are unable to explain fully.Nevertheless, the 51 V NMR spectroscopy proved to be very useful means, which helps to reveal the changes occurred in solution.

Infrared spectroscopy
The selected characteristic IR bands of the prepared compounds are summarized in Table S2.Both compounds exhibit typical strong bands corresponding to vibrations of the coordinated carboxylate ligands and to the V=O stretching vibrations (Figure S3 and Figure S4 in Supporting Information).

UV-vis and CD spectra
The characteristic bands in the UV-vis spectrum of 2 in water appearing at 495 and 525 nm correspond to the MLCT transitions (Figure S2).The CD spectrum of 2 (Fig. 5) in aqueous solution exhibits well-distinguished bands.The spectrum fully corresponds to the of Δ-[Fe(bpy) 3 ] 2+ [27] a contribution originating in the chiral anion was not observed.The Δ-configuration of [Fe(bpy) 3 ] 2+ is thus in aqueous solution preserved (at least for some time).

Mössbauer spectroscopy
To exclude the option that a mixture of Fe(II) + Fe(III) is present in 2 and thus the charge is balanced with [Fe(bpy) 3 ] 3+ rather than H 3 O + , we collected a Mössbauer spectrum of 2 (Fig. 6).At first glance, the spectrum looks like a simple doublet from one kind of Fe atom in the sample, which corresponds to a magnetically disordered structure (paramagnetic or diamagnetic state).However, this doublet spectrum is slightly asymmetric (ratio D21 = D2: D1 = 0.93), which may be caused by non-equivalent vibrations in individual lattice axes or the presence of another type of Fe atom.From the previous knowledge of the structure of the given sample, the presence of two iron atoms in the structure can be assumed, and therefore the asymmetry of the doublet was attributed to two types of Fe atoms with different environments around them.The Mössbauer spectrum was described by two subspectra with a Lorentzian profile, which correspond to two Fe atoms with different surroundings.The shape of the spectrum already indicates the distribution of electric charge around the Fe core present in the sample.The doublet subspectrum corresponds to an inhomogeneous distribution of electric charge around the Fe nucleus, whereas the singlet corresponds to a more homogeneous distribution around the Fe nucleus.The obtained values of isomer shift, δ = 0.296(4) mm/s, and quadrupole splitting, ΔE Q = 0.328(9) mm/s are typical for the oxidation state of iron Fe 2+ in a low-spin complex with octahedral coordination [28,29].The singlet subspectrum is characterized by an isomeric shift, δ = 0.32(2) mm/s, also corresponding to the iron 2 + oxidation state atom.From the depth of both sub-spectra (surface under the curve), the percentage representation of both Fe atoms in the sample can be attributed, which corresponds to 82.2 and 17.8%, for Fe 2+ with an inhomogeneous environment and Fe 2+ with a homogeneous environment, respectively.

Conclusions
The MVO 3 (M=Na, K, NMe 4 , NEt 4 )-mandelic acid-H 2 O-(co-solvent) systems are prone to undergo redox processes by the formation of vanadium(IV) compounds.The synthesis and storage of the vanadium(V)-mandelato complexes including these cations necessitate the employment of temperature about −20 °C.In contrast, similar systems containing [Fe(bpy) 3 ] 2+ are stable against redox reactions.Consequently, although compounds 1 and 2 have been prepared at 5 °C in order to obtain better crystals, these compounds can actually be synthesized and stored at room temperature.
The peculiarity of synthesizing 2 stems from the fact that the V 3 L 2 complex is always a minor species in solution; only the proper interplay of experimental factors (molar ratio and concentration of reacting compounds, duration of the reactions, the composition of solvent, access to surroundings atmosphere etc.) can lead to successful syntheses.We carried out numerous attempts to obtain single crystals of 2 by liquid-to-liquid diffusion strategies in closed vials, but all these attempts ended with failure.Only attempts with conducting reactions in covered beakers and accompanied by changing the solvent composition (preferential evaporation of CH 3 CN) and by the formation of precipitates led to positive results.
Compound 2 is the second example of a vanadium(V)mandelato complex of the V 3 L 2 type.Contrarily to our previous results using NH 4 + and NEt 4 + as the counter ions, where we prepared the V 3 L 2 complex only with racemic mandelic acid, the presence of the [Fe(bpy) 3 ] 3+ ions enabled the synthesis of the V 3 L 2 complex only with (S)-mandelic acid.Due to the complexity of reaction systems mentioned above, we were unable to disclose the reasons for such a stereospecific behaviour.In addition, to the differences in reaction solutions revealed by NMR spectroscopy, we expect that also the crystallochemical properties of crystalline phases contribute to the stereospecific formation of the vanadium(V) mandelato complexes.The atoms of the darker bpy ligand exhibit occupancies roughly 28%, while the atoms of the bpy ligand in a more disordered position exhibit occupancy of roughly 72%

Fig. 7
Fig. 7 Ball and stick model of the [Fe(bpy) 3 ] 2+ cation present in 2.The atoms of the darker bpy ligand exhibit occupancies roughly 28%, while the atoms of the bpy ligand in a more disordered position exhibit occupancy of roughly 72%

Table 1
Crystal structure solution and refinement data