Dioxomolybdenum(VI) chelates of bioinorganic, catalytic, and medicinal relevance: Studies on some cis-dioxomolybdenum(VI) complexes involving O, N-donor 4-oximino-2-pyrazoline-5-one derivatives

2.1 Materials

3-Methyl-1-phenyl-2-pyrazolin-5-one- (Lancaster, UK), benzoyl chloride, acetyl chloride and propionyl chloride, hydroxylamine hydrochloride, acetylacetone, calcium hydroxide (Thomas Baker Chemicals Limited, Mumbai), butyryl chloride, iso-butyryl chloride (Merck, Germany) and Sodium hydroxide (E. Merck India Limited, Mumbai), ammonium molybdate tetrahydrate (Sisco Chem. Industries, Mumbai) were used as supplied. Alcohol was purchased from Bengal Chemicals and Pharmaceuticals Limited, Kolkata. All other chemicals used were of analytical reagent grade.

2.2 Preparation of parent compound

The parent compound bis(acetylacetonato)dioxomolybdenum(VI), [MoO₂(acac)₂] was prepared by the method of Chen et al. (Chen et al., 1976).

2.3 Preparation of different 4-acyl-3-methyl-1-phenyl-2-pyrazolin-5-one

They were prepared by the Jensen’s (Jensen, 1959) method with slight modification. Into a one liter 3-necked quick fit flask containing DMF (100 mL) and carrying a dropping funnel, a mechanical stirrer, and a reflux condenser, was placed 3-methyl-1-phenyl-2-pyrazolin-5-one (17 g, 0.098 M). A solution was obtained by gentle heating, and benzoyl chloride (12 mL)/acetyl chloride (5.4 mL)/propionyl chloride 8.94 mL)/butyryl chloride (10.33 mL)/isobutyryl chloride (11 mL) was added drop wise within 2–3 min. The reaction was exothermic and the reaction mixtures became a paste. The mixture was allowed to cool and then refluxed with stirring for 1 h on a sand bath, during which period the bright yellow complex formed initially turned yellowish brown. The complex was decomposed by pouring the reaction mixture into chilled dilute hydrochloric acid solution (500 mL, 3 N). A yellowish brown solid settled, which was filtered in a sintered glass crucible, washed with distilled water until the washings were colorless, and dried in air and recrystallized from n-heptane. Some important physical properties are given in the Table 1.

The reaction scheme related to the synthesis of 4-acyl-3-methyl-1-phenyl-2-pyrazolin-5-one is as follows (Scheme 1.).

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Scheme 1

Reaction scheme for the synthesis of 4-acyl-3-mthyl-1-phenyl-2-pyrazolin-5-one derivatives.

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2.4 Preparation of oxime derivatives of bmppH, bumppH, amppH, pmppH, iso-bumppH

These oximes were prepared by following the general method given below: A solution of hydroxylamine hydrochloride (0.347 g, 5 mmol) and sodium hydroxide (0.20 g, 5 mmol) in 40 mL aqueous/ethanol (1:1) was added to a solution of 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (1.39 g, 5 mmol), 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one (1.08 g, 5 mmol), 3-methyl-1-phenyl-4-propionyl-2-pyrazolin-5-one (1.15 g, 5 mmol), 4-butyryl-3-methyl-1-phenyl-2-pyrazoline-5-one (1.22 g, 5 mmol), or 4-iso-butyryl-3-methyl-1-phenyl-2-pyrazolin-5-one (1.22 g, 5 mmol) in 20 mL ethanol. The mixture was refluxed for two hours. On cooling a crystalline product was obtained, which was filtered by suction, washed several times with water and finally with ethanol. The oxime of 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one was precipitated by pouring the reaction mixture in excess (150 mL) of distilled water. The characterization data of the oxime derivatives are given in Table 2.

2.5 Preparation of complexes

The oximes derivative, bomppH (0.586 g, 2 mmol), aomppH (0.462 g, 2 mmol), mppopH (0.490 g, 2 mmol), buomppH (0.518 g, 2 mmol) or ibuomppH (0.518 g, 2 mmol) was dissolved by heating in 20 mL of ethanol. To this solution, an ethanolic solution (10 mL) of bis(acetylacetonato)dioxomolybdenum(VI) (0.326 g, 1 mmol) was added. The resulting solution was refluxed for 10–12 h and then concentrated to half of its volume. The resulting precipitate was suction filtered and washed several times using 1:1 ethanol–water and dried in vacuo. The analytical data of the complexes are given in Table 3.

2.6 Analyses

Carbon, hydrogen, and nitrogen were determined micro-analytically at the Central Drug Research Institute, SAIF, Lucknow. The metal content in each chelate was determined (Maurya et al., 1993) as follows: A weighed amount (∼200 mg) of the chelate was first decomposed by heating with concentrated nitric acid and then strongly heating the residue over 800 °C for 1 h until a constant weight was obtained. The residue was weighed as MoO₃.

2.7 Physical methods

Electronic spectra of the complexes were recorded in dimethylformamide on an ATI Unicam UV-2–100 UV/visible spectrophotometer in our Department. ¹H NMR spectra of compounds were recorded in DMSO-d₆ at Central Drug. Research Institute, SAIF, Lucknow. The solid-state infrared spectra were recorded in KBr pellets using Perkin–Elmer model 1620 FT-IR spectrophotometer at the Indian Institute of Technology, Roorkee and also on FT-IR 8400S SHIMADZU at our own Department. Conductance measurements were done at room temperature in dimethylformamide using a Toshniwal Conductivity Bridge and dip type cell with a smooth platinum electrode of cell constant 1.02. Decomposition temperatures of the oxime derivatives and chelates were recorded using an electrothermal apparatus having the capacity to record temperature up to 360 °C. Thermogravimetric analyses of the samples were done at SAIF, Indian Institute of Technology, Mumbai. Mass spectra were recorded at Sophisticated Analytical Instrumentation Facility, CDRI. Lucknow. Magnetic measurement was performed by the Vibrating Sample Magnetometer method.

2.8 Molecular modeling studies

The 3D molecular modeling of a representative compound was carried out on a CS Chem 3D Ultra Molecular Modeling and Analysis Program (www.cambridgesoft.com). It an interactive graphics program that allows rapid structure building, geometry optimization with minimum energy and molecular display. It has ability to handle transition metal compounds.

3.1 Composition and characterization of the oxime derivatives

The oxime derivatives used in the present investigation were prepared as shown in reaction scheme given in Scheme 2.

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Scheme 2

Synthesis of oxime derivatives.

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The compositions of the ligands are consistent with the micro-analytical data. The IR spectra of these oximino derivatives have a band at 1660–1685 cm⁻¹, which is assigned to ν(C⚌O) (cyclic) of the pyrazolone skeleton. A strong band at 1610–1656 cm⁻¹ in these derivatives is assigned to v(C⚌N) (oxime). Another strong band observed in all the oxime derivatives at 1590–1602 cm⁻¹ is most probably due to ν(C⚌N) (cyclic) of the pyrazolone skeleton. All the oxime derivatives show medium/broad bands with fine structure in the range 3040–3451 cm⁻¹, which may be due to v(OH) of the oxime group. The observed low value of v(OH) suggests the presence of intramolecular hydrogen bonding in the derivatives. A new band observed at 1010–1044 cm⁻¹ in the oxime derivatives, unlike the parent carbonyl compound, may be assigned to v(N–O). The overall IR results conclude that all the oxime derivatives exist in ketonic form in the solid state as shown in the scheme above.

The proton NMR spectra of two representative ligands namely mppopH (II) (Fig. 4) and buomppH (III) (Fig. 5) were recorded in DMSO-d₆. The proton signals due to aromatic protons of the phenyl ring in the two ligands displayed as multiplets in the region δ 7.194–7.913 and δ 7.173–7.939 ppm, respectively. The other proton signals in case of ligand (II) at δ 2.740–2.789 (quartet), δ 2.342 (singlet) and at δ 1.051–1.140 (triplet) ppm are most probably due to proton groups, such as –CH₂ (b), –CH₃ (a), and –CH₃ (c), respectively. In case of the ligand (III) proton signals at δ 2.642–2.858 (multiplets), δ 2.317 (singlet), δ 1.576–1.623 (triplet) and δ 0.902–0.927 (triplet) ppm are due to proton groups likely to be –CH₂ (c), –CH₃ (a), –CH₂ (b) and –CH₃ (d), respectively. Both the ligands displayed two singlet proton signals at δ 10.240–10.422 and δ 10.986–11.101 ppm most probably due to enolic (OH) (cyclic) and –NOH (oxime), respectively. The indexing of various protons is given in Fig. 6.

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Figure 4

¹H NMR spectrum of mppopH (II).

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Figure 5

¹H NMR spectrum of buomppH (III).

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Figure 6

Indexing of various protons in ligands II and III.

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The presence of a proton signal at δ 10.240–10.422 ppm suggests that the ligand exist in enolic form in DMSO-d₆ (solvent used for NMR). Contrary to this, all the ligands exist in ketonic form in the solid state as concluded from the IR spectral studies discussed above.

3.2 Characterization of complexes

The formation of metal chelates can be represented by the following general equation: $$\begin{array}{cc}\hfill & [{\text{MoO}}_2{(\text{acac})}_2]+2\text{LH}\underset{\text{Reflux}}{\overset{\text{Ethanol}(95\%)}{⟶}}[{\text{MoO}}_2{(\text{L})}_2({\text{H}}_2\text{O})]\hfill \\ \hfill & +2\text{acacH}\hfill \\ \hfill & \text{where LH}=\text{aomppH,mppopH,buomppH,ibumppH}\text{or}\hfill \\ \hfill & \text{bomppH}\hfill \end{array}$$ The driving force for the reaction in order to form these chelates along with the elimination of two molecules of acetylacetone (acacH) is the better donating (Maurya et al., 2003c) capability of the oxime derivatives compared to acetylacetone anion.

The synthesized complexes are colored, non-hygroscopic and air stable solids. They are thermally stable and their decomposition temperatures are given in the Table 4. These are soluble in dimethylformamide and dimethylsulfoxide, and insoluble in all other common organic solvents. Some physical properties of the complexes are also given in Table 4. The formulations of these complexes are based on their elemental analyses, infrared spectra, magnetic measurements, NMR, mass, thermogravimetry, and electronic spectral studies.

3.3 IR spectral studies

The MoO₂²⁺ moiety prefers to form a cis-dioxo grouping due to the maximum utilization of the d-orbital for bonding. The dioxo-configuration is characterized by two infrared active modes of ν_s(O⚌Mo⚌O) and ν_as(O⚌Mo⚌O) in C_2V symmetry. The trans-MoO₂²⁺ moiety would exhibit a single infrared active stretching band of ν_as(O⚌Mo⚌O). The presence of two infrared bands in the 910–913 and 941–991 cm⁻¹ regions due to ν_as(O⚌Mo⚌O) and ν_s(O⚌Mo⚌O), respectively, in the present complexes is strongly indicative of the cis-MoO₂²⁺ structures (Syamal and Maurya, 1989; Maurya et al., 1995a).

The coordination of oxime nitrogen is inferred by a shift to lower frequencies⁵⁷ (Maurya et al., 2003d) in the ν(C⚌N) (Oxime) (1567–1578 cm⁻¹) in all the complexes as compared to that of the free oxime derivatives at 1610–1656 cm⁻¹. This is further supported by shifting of the ν(N–O) to a higher wave number (1073–1091 cm⁻¹) (Yildim et al., 2003; Maurya et al., 2003d; Karatas et al., 1991c) in the complexes as compared to that of the free oxime derivatives appearing at 1010–1044 cm⁻¹. All the oxime derivatives display a band in the region of 1590–1602 cm⁻¹, which may be due to ν(C⚌N²) (pyrazoline ring). This band remains almost unchanged in all the metal chelates. This indicates that the ring nitrogen N² does not take part in coordination, which is in agreement to our previous observation (Maurya et al., 2003b). The absence of a strong band at 1660–1685 cm⁻¹ due to ν(C⚌O) and the appearance of a new band in the region of 1126–1227 cm⁻¹ assignable to ν(C–O) (enolic), may be taken as diagnostic of coordination of cyclic oxygen to the metal center in the enol form (Kharodawala and Rana, 2003; Maurya et al., 2007) after deprotonation. The coordination of oxime nitrogen and cyclic oxygen is further supported by the appearance of two non-ligand bands at 508–517 and 430–497 cm⁻¹ assignable to ν(M–O) and ν(M–N), respectively (Maurya et al., 2003a).

The IR spectra of all the complexes show a broad band centered at 3375–3437 cm⁻¹. This suggests the presence of coordinated water molecules. A weak band at 1658–1724 cm⁻¹ in the IR spectra of all the complexes can be ascribed to the inter-molecular hydrogen bonded O–H⋯O (between oxime OH group and coordinated water oxygen) bending vibration (Chakravorty, 1974). The important infrared spectral bands of the oxime derivatives and complexes in the present investigation are given in Tables 3 and 5, respectively. The IR spectra of the ligand, mppopH (II), and its complex [MoO₂(mppopH)₂(H₂O)₂] (2) are given in Figs. 7 and 8, respectively.

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Figure 7

IR spectrum of mppopH (II).

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Figure 8

IR spectrum of [MoO₂(mppopH)₂(H₂O)₂] (2).

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3.4 ¹H NMR spectral studies

The ¹H NMR spectrum of a representative compound [MoO₂(buomppH)₂(H₂O)₂] (3) (Fig. 9) was recorded in DMSO-d₆ to compare its result with the respective ligand. The absence of an enolic proton (cyclic) signal at δ 10.422 in the ligand was found to be absent in the spectrum of this complex. This shows the coordination of enolic oxygen after deprotonation to the metal center in this complex. This is in agreement with the IR spectral results related to the coordination of ligands under discussion. Other proton signals in the complex are δ 2.424 (singlet) –CH₃ (a), δ 1.577–1.625 (triplet) –CH₂ (b), δ 2.595–2.912 (multiplets) –CH₂ (c), δ 0.916–0.969 (triplet) –CH₃ (d) and δ 7.268–8.144 (multiples) (aromatic protons).

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Figure 9

¹HNMR spectrum of [MoO₂(buomppH)₂(H₂O)₂] (3).

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Two more proton signals were observed at δ 12.501 and δ 13.173 ppm in this complex, which are most probably due to protons of hydrogen bonded coordinated water molecules, and hydrogen bonded oxime proton (Zulfikaroglu et al., 2003), respectively.

3.5 Electronic spectral studies

Electronic spectra of all the complexes were recorded in 10⁻³ M in dimethylformamide solutions. The electronic spectral peaks observed in each of the complexes along with their molar extinction coefficient are given in Table 6. The high intensity spectral peak in UV-region in each of the complexes is due to intra-ligand transition. A medium to weak intensity peak near 443–444 nm in complexes (2) and (4) may be due to the ligand to metal charge transfer transitions (LMCT). The nonappearance of the LMCT band in the other three complexes is most probably due to its poor intensity. The electronic spectrum of [MoO₂(ibuomppH)₂(H₂O)₂] (4) is given in Fig. 10.

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Figure 10

Electronic spectrum of [MoO₂(ibuomppH)₂(H₂O)₂] (4).

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3.6 Thermogravimetric studies

The thermogravimetric curves of two representative compounds [MoO₂(mppopH)₂(H₂O)₂] (2) (Fig. 11) [MoO₂(buomppH)₂(H₂O)₂] (3) (Fig. 12) were recorded in the temperature range of 25–1000 °C at the heating rate of 15 °C per minute. The compound (2) shows a weight loss of 5.3% at 300 °C with start of weight loss at 240 °C, corresponding to the elimination of two moles of coordinated water (calcd. weight loss for two mole H₂O = 5.52%). It shows a second weight loss of 42.2% at 587 °C corresponding to the elimination of one coordinated oxime ligand group (calcd. weight loss of one oxime ligand group = 42.94%). The final weight loss (obs. = 80.0%) at 778.12 °C corresponds to the elimination of one mole oxime ligand group (calcd. weight loss = 80.37%). The final residue at ∼780 °C (obs. = 20.0%) corresponds to MoO₃ (calcd. = 22.07%).

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Figure 11

TG curve of [MoO₂(mppopH)₂(H₂O)₂] (2).

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Figure 12

TG curve of [MoO₂(buomppH)₂(H₂O)₂] (3).

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Similar to compound (2), the compound (3) displayed the following three weight losses:

The final residue at ∼780 °C (obs. = 21.0%) corresponds to MoO₃ (calcd. = 21.03%). As the MoO₃ is known to volatilize above 800 °C (melting point 795 °C (Greenwood and Earnshaw, 1984) and loose the weight, the TG plots will never be flat if these were reordered up to 1000 °C. Hence, both the TG plots appeared to be effectively recorded up to 800 °C, and so these are flat after ca. 750 °C.

3.7 Mass spectral studies

The FAB mass spectrum of a representative compound [MoO₂(buomppH)₂(H₂O)] (3) (Fig. 13) is recorded on a JEOL SX 102/DA-6000 Mass Spectrometer/Data system using argon/xenon (6 KV, 10 mA) as the FAB gas. The accelerating voltage was 10 KV and the spectrum was recorded at room temperature. m-Nitrobenzyl alcohol (NBA) was used as the matrix. The matrix peaks were supposed to appear at m/z 136, 137, 154, 289, 307 in the absence of any metal ion. If metal ions are present, these peaks may be shifted accordingly.

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Figure 13

Mass spectrum of [MoO₂(buomppH)₂(H₂O)₂] (3).

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The mass spectral peaks observed at 136 and 154 m/z are matrix peaks. The spectral peak observed at 257, 513, 370, 387, 600, and 542 m/z are most probably due to the following types of ion associations:

1. [buomppH]⁺ (258) − H⁺ = 257

2. [buomppH]⁺ (258) + (Mo = O)⁺ (111.94) = 370

3. [buomppH]⁺ (258) + [O⚌Mo⚌O]⁺ (127.94) + H⁺ = 387

4. 2[buomppH]⁺ (516) − 3H⁺ = 513

5. [Base peak]⁺ (600) − ^∗[C₃H₇]⁺ (43) − ^∗[CH₃]⁺ (15) = 542

6. [Molecular ion]⁺ (643.94) − ^∗[C₃H₇]⁺ (43) = 600 (Base peak)

^∗From butyryl oxime

These results are consistent with the proposed molecular composition of the complex (3).

3.8 Conductance measurements

The molar conductivities of all the complexes in 10⁻³ M DMF solution are in the range 10.1–15.2 ohm⁻¹ cm² mol⁻¹ (Table 4) as expected for non-electrolytes (Geary, 1971). Such a non-zero molar conductance value for each of the complexes in the present study is most probably due to the strong donor capacity of DMF, which may lead to the displacement of the anionic ligand and change of electrolyte type.

3.9 3D Molecular modeling and analysis

Based on the proposed structures (Fig. 15), the 3D molecular modeling of one of the representative compounds, viz., [MoO₂(aomppH)₂(H₂O)₂] (1), was carried out with the CS Chem 3D Ultra Molecular Modeling and Analysis Programme. The details of bond lengths, bond angles as per the 3D structure (Fig. 14) are given in Tables 7 and 8, respectively. For convenience of looking over the different bond lengths and bond angles, the various atoms in the compound in question are numbered in Arabic numerals. In all, 243 measurements of the bond lengths (83 in number), plus the bond angles (160 in number) are listed in the Tables 7 and 8. Except a few cases, optimal values of both the bond lengths and the bond angles are given in the Tables along with the actual ones. The observed bond lengths/bond angles given in the Tables are calculated values as a result of energy optimization in CHEM 3D Ultra [44], while the optimal bond length/optimal bond angle values are the most desirable/favorable (standard) bond lengths/bond angles established by the builder unit of the CHEM 3D. The missing of some values of standard bond lengths/bond angles may be due to the limitations of the software, which we had already noticed in the modeling of other systems (Maurya and Rajput, 2006; Maurya et al., 2008, 2010). In most of the cases, the observed bond lengths and bond angles are close to the optimal values, and thus the proposed structure of compound (1) (and also others) is acceptable (Maurya and Rajput, 2006; Maurya et al., 2008, 2010).

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Figure 15

Proposed structure of complexes.

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Figure 14

3D structure of compound (1).

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