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Home > Pyrazole Based Mono- and Di-Substituted Half Sandwich d6 Platinum Group Metal Complexes: Synthesis and Spectral Characterization
Pyrazole Based Mono- and Di-Substituted Half Sandwich d6 Platinum Group Metal Complexes: Synthesis and Spectral Characterization
Basava Punna Rao Aradhyula,[a] Ibaniewkor L. Mawnai,[a] and Mohan Rao Kollipara
1 Introduction
Half-sandwich d6 metal complexes have emerged as versatile intermediates in the organic chemistry synthesis due to the availability of three labile coordinate sites and rigid arene ring occupying another three coordinate sites.[1,2] In these systems the nature of the arene, the chelating ligands, and the leaving group in these complexes strongly influence their chemical and biological activity and exhibit structure–activity relationships.[3]
Among the half-sandwich complexes, ruthenium complexes represent one of the most sought-after organometallic compounds due to their potential applications in various areas.[4–7] In recent years arene RuII complexes have attracted more attention in chemotherapy because of their low toxicity and excellent inhibitory activity against tumor cell. Furthermore, many half-sandwich ruthenium complexes with various N-based ligands such as [N, N],[8] [N, O],[9–11] [N, C],[12–14] [N, P],[15,16] [N, S], and [N, Se][17,18] have been synthesized and applied to various organic transformations. Recently, the isoelectronic cyclopentadienyl RhIII and IrIII complexes have also been shown to have highly potent anticancer activity.[19–23]
We are currently interested in the coordination chemistry of pyrazole derived ligands because of their unusual structural features and remarkable physical and chemical properties.[24] One of the important structural feature of these pyrazoles is existence of annular tautomerism such phenomenon promotes the pyrazole based ligands to coordinate the metal atoms in a steric free manner.[25,26] Their importance is attributed to their rich electronic property, which can be altered by appropriate choice of substituents on the pyrazole ring, which in turn enables optimization of the electronic properties on the metal.
Pyrazole derivatives exhibit broad spectrum of pharmacological activities[27,28] like anti-inflammatory,[29] anticonvulsant,[30] anticancer,[31] and antifungal[32] behavior. Initially Ward et al. have reported many coordination architectures through 3-(2-pyridyl) pyrazole based ligands.[33] Previous studies in this laboratory have reported many halfsandwich ruthenium, rhodium, and iridium complexes with
various pyrazole-based ligands such as pyrazolyl-pyrimidine, pyrazolyl-pyridazine, pyrazolyl-pyridine, thienyl and furyl pyrazole, and pyrazolyl-quinoxaline.[34] In continuation to our previous work, herein we report the synthesis and characterization of a series of mono and bis substituted pyrazole based half-sandwich d6 metal complexes with 5-(4-bromophenyl)-1H-pyrazole ligand. Aryl halides are crucial precursors for the coupling reactions; these bromo-substituted complexes could serve as precursors for the design of metallacycles.
2 Experimental Section
2.1 Materials and Methods
4-Bromoacetophenone, dimethylformamide dimethyl acetal (DMFDMA), and hydrazine hydrate were purchased from Sigma–Aldrich and used as received. All the solvents used for synthesis were dried
and distilled prior to use according to the standard procedures and stored over activated molecular sieves.[35] Starting precursors [(benzene)RuCl2]2, [(p-cymene)RuCl2]2, [Cp*RhCl2]2 and [Cp*IrCl2]2, and ligand (L) were prepared according to the literature methods.[36–41] The elemental analyses were performed with a Perkin–Elmer-2400 CHN analyzer. The electronic absorption spectra of the compounds were recorded with a Perkin–Elmer Lambda 25 absorption spectrophotometer and the solvent used was acetonitrile. IR spectra were recorded with a Perkin–Elmer 983 model FT-IR spectrophotometer with compounds being pressed as KBr discs. All 1 H NMR spectra were recorded with a Bruker Avance II 400 MHz spectrometer at room temperature in CDCl3 and [D6]DMSO; chemical shifts are referenced
to resonances of the deuterated solvents. ESI-MS was carried out with a Bruker micro TOF-Q II using acetonitrile as the solvent.
2.2 X-ray Data Collection, Structure Solution, and Refinement
Crystals of complexes 1–8 were grown by slow diffusion of hexane into acetone or dichloromethane (DCM) solutions of the complexes and isolated as orange and pale-yellow blocks. The crystallization was
done at ambient temperature. Suitable single crystals were selected under the microscope and immersed in inert oil to prevent losing solvent molecule (mostly DCM as solvent) from crystals. The crystals
were mounted on a glass capillary and attached to a goniometer head on an Xcalibur, Eos, Gemini diffractometer equipped with graphitemonochromated Mo-Kα radiation (λ = 0.71073 Å). The full data sets
were recorded and the images processed using the Crys Alis Pro.[42]
Structure solution by direct methods was achieved through the use of the SHELX program,[43] and the structural model refined by full-matrix least-squares on F2 using SHELX.[44] The non-hydrogen atoms
were refined with anisotropic thermal parameters. Hydrogen atoms were placed using idealized geometric positions (with free rotation for methyl groups), allowed to move in a “riding model” along with the atoms, to which they were attached, and refined isotropically. Molecular graphics were plotted using POVray via ORTEP-3[45] for Windows. ORTEP presentations of the representative complexes are shown in Figure 1, Figure 2, and Figure 3. The data collection and refinement parameters are summarized in Table 1 and Table 2. Bond lengths and angles are listed in Table 3.
Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre, CCDC, 12 Union Road, Cambridge CB21EZ, UK. Copies of the data can be obtained free of charge on quoting the depository numbers CCDC-1852616 (1), CCDC-1852617 (2), CCDC-1852618 (3), CCDC-1852621 (5), CCDC-1852620 (7), and CCDC-1852622 (8) (Fax: +44-1223-336-033; E-Mail: deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk).
2.3 General Procedure for the Synthesis of Mononuclear Complexes 1–8
The reaction of precursor [(arene)MCl2]2 complexes (0.08 mmol) with the ligand (L) (0.16 mmol for mono-substituted and 0.32 mmol for disubstituted) in DCM (20 mL) were stirred for 4–6 h. During the course of the reaction, the color of the solution changed from red to orange yellow. The solution was filtered through a bed of celite to remove the undissolved materials and the solvents evaporated. The resulting residue was washed with diethyl ether (210 mL) and the precipitates were air-dried. All the complexes were soluble in polar organic solvents viz., acetone, dichloromethane (DCM), chloroform, acetonitrile but are insoluble in non-polar organic solvents viz., hexane, benzene, and toluene.
2.3.1 [(benzene)RuCl2L] (1)
Yield: 47%. IR (KBr): ν˜ = 3434 (νN–H), 1639 (νC=C), 1432 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 12.94 (s, 1 H), 8.26 (d, J = 4 Hz, 1 H), 7.75 (d, J = 8 Hz, 2 H), 7.56 (d, J = 8 Hz, 2 H), 6.69 (d, J = 4 Hz, 2 H), 5.97 (s, 6 H, CH(benzene)). ESI-MS (m/z): 321.26 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 420, 256.
2.3.2 [(p-cymene)RuCl2L] (2)
Yield: 55%. IR (KBr): ν˜ = 3430 (νN–H), 1636 (νC=C), 1460 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 12.01 (s, 1 H,NH), 7.92 (d, J = 4 Hz, 1 H), 7.55 (d, J = 12 Hz, 2 H), 7.36 (d, J = 8 Hz, 2 H), 6.63 (d, J = 4 Hz, 1 H), 5.58 (d, J = 4 Hz, 2 H, CH(p–cym)), 5.41 (d, J = 8 Hz, 2 H, CH(p–cym)), 3.02 (sep, 1 H), 2.30 (s, 3 H, CH(p–cym)), 1.31 (d, J = 8 Hz, 6 H). ESI-MS (m/z): 377.11 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 408, 256.
2.3.3 [Cp*RhCl2L] (3)
Yield: 53%. IR (KBr): ν˜ = 3443 (νN–H), 1625 (νC=C), 1462 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 12.19 (s, 1 H, NH), 8.12 (t, J = 2·Hz, 1 H), 7.96 (d, J = 2 Hz, 2 H), 7.55 (d, J = 8 Hz, 2 H), 6.60 (t, J = 4 Hz, 1 H), 1.70 (s, 15 H, CH(Cp*)). ESI-MS (m/z): 379.21 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 344, 261.
2.3.4 [Cp*IrCl2L] (4)
Yield: 50%. IR (KBr): ν˜ = 3434 (νN–H), 1637 (νC=C), 1467 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 12.34 (s, 1 H, NH), 7.72 (d, J = 4 Hz, 1 H), 7.55 (d, J = 4 Hz, 2 H), 7.50 (d, J = 8 Hz, 2 H), 6.55
(d, J = 4 Hz, 1 H) 1.60 (s, 15 H, CH(Cp*)). ESI-MS (m/z): 469.87 [M –Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 355, 258.
2.3.5. [(benzene)RuClL2]Cl (5)
Yield: 45%. IR (KBr): ν˜ = 3434 (νN–H), 1634 (νC=C), 1459 (νC=N) cm–1. 1 H NMR (400 MHz, [D6]DMSO): δ = 12.95 (s, 2 H, NH), 7.75 (d, J = 8 Hz, 4 H), 7.57 (d, J = 8 Hz, 4 H), 7.35 (d, J = 2 Hz, 2 H), 6.73 (d, J = 2 Hz, 2 H), 5.95 (s, 6 H, CH(benzene)). ESI-MS (m/z): 465.05 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 411, 259.2.3.6.
2.3.6 [(p-cymene)RuClL2]Cl (6)
Yield: 54%. IR (KBr): ν˜ = 3444 (νN–H), 1635 (νC=C), 1467 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 14.90 (s, 2 H, NH) 8.11 (d, J = 2 Hz, 2 H), 7.96 (d, J = 8 Hz, 4 H), 7.62 (d, J = 12 Hz, 4 H), 6.55 (d, J = 4 Hz, 2 H, CH(p–cym)), 6.06–6.11(dd, J = 4 Hz, 8 Hz, 2 H, CH(p–cym)), 2.20 (sep, 1 H, CH(p–cym)), 1.80 (s, 3 H, CH(p–cym)), 1.14 (d, J = 8 Hz, 6 H). ESI-MS (m/z): 521.07 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 410, 258.
2.3.7 [Cp*RhClL2]Cl (7)
Yield: 52%. IR (KBr): ν˜ = 3430 (νN–H), 1638 (νC=C), 1458 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 15.14 (s, 2 H,NH), 8.14 (d, J= 2 Hz, 2 H), 7.98 (d, J = 8 Hz, 4 H), 7.61 (d, J = 8 Hz, 4 H) 6.62 (d, J = 4 Hz, 2 H), 1.69 (s, 15 H, CH(Cp*)). ESI-MS (m/z): 524.23 [M –Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 406, 256.
2.3.8 [Cp*IrClL2]Cl (8)
Yield: 52%. IR (KBr): ν˜ = 3459 (νN–H), 1634 (νC=C), 1467 (νC=N) cm–1. 1 H NMR (400 MHz, CDCl3): δ = 15.09 (s, 2 H,NH), 8.05 (d, J= 4 Hz, 2 H), 7.87 (d, J = 8 Hz, 4 H), 7.51 (d, J = 8 Hz, 4 H), 6.51 (d, J = 2 Hz, 2 H), 1.55 (s, 15 H, CH(Cp*)). ESI-MS (m/z): 616.97 [M – Cl2-Br]+. UV/Vis {acetonitrile, λmax (nm) (10–4 m–1·cm–1)}: 420, 257. Supporting Information (see footnote on the first page of this article):
Supporting Information contains IR, proton NMR and mass spectral data.
3 Results and Discussion
3.1 Synthesis of the Ligand
3-(4-Bromophenyl)-1H-pyrazole was synthesized by the reaction of appropriate ratio of 4-bromoacetophenone with DMF-DMA and hydrazine hydrate that undergoes tautomerism giving 5-(4-bromophenyl)-1H-pyrazole as represented in Scheme 1. This is confirmed by the absence of NH signal in the 1 H NMR spectrum of the ligand. On complexation, the ligand prefers to bind to the central metal atom through neutral nitrogen N1 rather than nitrogen (N2) having proton in the case of mono substituted complexes. The same is also observed in the case of di-substituted complexes, where the ligand prefers to bind through neutral nitrogen N1.
3.2 Synthesis of the Complexes
Treatment of d6 configured halo-bridged metal dimers and the pyrazole ligand in 1:2 and 1:4 ratio resulted in the formation of mono- and di-substituted metal complexes (Scheme 2). The complexes were isolated as yellow and yellow orange solids with moderate yields. However the yield of benzene complexes is less due to their insoluble nature of the precursor complex. Mono substituted complexes are isolated as neutral complexes, whereas the di-substituted complexes are obtained as cationic complexes with chloride as a counterion. Complexes 1–8 are stable at room temperature and are soluble in
polar organic solvents but insoluble in nonpolar solvents. The antibacterial activity of the synthesized complexes was studied but these complexes did not show any activity even at higher concentrations of the complexes. At present it is difficult to predict specifically, which type of structure or group will enhance the activity of the complexes but it may be suggested that substituting the bromide group with amino or methoxy groups might enhance the activity of the complexes as reported in the literature.[31]
3.3 Characterization of the Complexes
3.3.1 IR Spectroscopy
The IR spectra of the complexes show some broad and strong bands in the region 3428 cm–1 to 1426 cm–1. The band at around 3400 cm–1 indicates the presence of N–H groups, which strongly supports that complexation occur through the neutral nitrogen of the pyrazole ring. The sharp bands at 1590 cm–1 and 1440 cm–1 represent the stretching frequencies of C=C and C=N bonds of the complexes.
3.3.2 1 H NMR Spectroscopy
The 1 H NMR spectra of the complexes 1–8 show a singlet in the range 12.1–15.14 ppm, which is attributed to the N-H proton signals. The appearance of the N-H signal in all the complexes indicates that the protic nitrogen is not involved in bonding. This is in good agreement with the appearance of NH stretching frequency as revealed from FT-IR spectroscopy. The aromatic proton signals associated with the ligand are observed as doublet in the range 7.35–7.98 ppm, whereas the proton, which is adjacent to the pyrazole nitrogen exhibits a doublet in the range of 7.91–8.14 ppm, which are downfield shift indicating the coordination of the ligand to the metal ion. The benzene proton resonance in complexes 1 and 5 is observed as a singlet at δ = 5.97 and 5.95 ppm, respectively. The aromatic proton signals of the p-cymene ligand in complexes 2 and 6 are observed as two doublets around 5.40–6.11 ppm, one septet around 2.20–3.02 ppm for the methine protons of the isopropyl group and a singlet around 1.80–2.30 ppm for the methyl protons and doublet around 1.13–1.30 ppm for the isopropyl group. In addition, a sharp singlet is observed for the rhodium and iridium complexes around 1.55–1.70 ppm for the methyl protons of the Cp* ligand. Furthermore, the formation of mono and di- substituted complexes is confirmed by the integral ratio of the ligand L with respect to the precursor complexes. In the
case of mono substituted complexes 1–4, the protons resonate with an integral ratio 1:1, whereas in the case of di-substituted complexes 5–8, the protons resonate with an integral ratio 1:2.
Such an integral ratio between the precursor protons and ligand protons clearly indicates the formation of mono- and di-substituted complexes of pyrazole.
3.3.3 Mass Spectrometry
The mass spectra of the complexes exhibit the characteristic peak as the loss of their halogen atoms unlike the [M]+ ions. Such [M–counterion / terminal halide]+ ions are generally observed in the half sandwich complexes rather than their molecular ion peak. For instance, the m/z values 377.11 (2), 465.05 (5), 521.07 (6), and 616.97 (8) are in corroboration with the expected [M – Cl1/2-Br]2+. [44,45] The appearance of these peaks in the mass spectra clearly indicates the formation of monoand di-substituted metal complexes. The mass spectral values strongly justify the composition and formulation of these complexes.
3.3.4 UV/Vis Studies
The electronic spectra of the complexes 1–8 along with the corresponding ligand L was recorded in acetonitrile solution at 20 μM concentration and is depicted in Figure 4. The free ligand exhibits a single characteristic band at around 260 nm. All the complexes exhibit a significant change in the intensity of the bands. In addition to the characteristic ligand band, the complexes also exhibit low intense band at around 400 nm. This is attributed to metal-to-ligand charge-transfer band. The appearance of these weak bands is due to the low concentration of the solution or obscured by the high intense ligand bands.[48,50] In order to observe these low intense bands, the high intense bands have been normalized.
3.4 Molecular Structures
Single crystals suitable for X-ray crystallographic analysis were obtained for all the complexes. The crystals were grown by slow solvent diffusion method where they crystallized from DCM/hexane or acetone/hexane solutions. The molecular structures of the complexes presented as ORTEP diagrams are depicted in Figure 1, Figure 2, and Figure 3. The relevant crystallographic parameters for the complexes 1–8 are presented in Table 1 and Table 2. The selected bond lengths and bond angles are listed in Table 3. Most of the complexes (2–6) crystallize in the monoclinic system with a P21/c (complexes 3–6) and P21/n (complex 2) space group. Complexes 7 and 8 crystallize in the orthorhombic system with space group P212121 whereas complex 1 crystallized in the triclinic system with
space group P1¯. Complexes 2–8 contain four molecules in their unit cell, whereas complex 1 contains two molecules in the unit cell. The molecular structure of these complexes featured a regular three legged piano-stool arrangement with metal coordinated by π-bonded arene ring (arene = p-cymene / benzene / Cp*) in a η6/η5 manner forming the stool, while chloride and pyrazole ligands forming the legs and the metal atoms are satisfied by the distorted octahedral arrangement around their vicinity.
The bond lengths and bond angles of the complexes are found to be closely related to the other reported half sandwich d6 metal complexes.[50,51] The metal–nitrogen bond lengths is found to be shorter in comparison to the metal to chloride bond lengths of the complexes. In neutral complexes 1–4 the widest bond angle is that between the two chlorine atoms, whereas in the cationic complexes 5–8 it is between the nitrogen atoms of the two-pyrazole ligands, which may arise due to the electronic repulsions of the similar moieties. In addition, the aromatic benzene ring of the pyrazole ligand is deviated from the coplanarity in the complexes. It may also be noted that the angle between the plane of the pyrazole and bromo substituted benzene ring in mono substituted ruthenium complexes (37.23° for
1 and 31.89° for 2) have more deviation in comparison to the higher congeners (15.45° for 3 and 15.83° for 4). When it comes to di-substituted complexes this interplanar angle between the pyrazole and benzene is almost coplanar with their minimal angles (2.71°, for 5, 9.86° for 6, 4.73° for 7, and 5.10° for 8) of one of the ligand.
4 Conclusions
We have isolated eight new mono- and di-substituted pyrazole based half sandwich d6 complexes. Complexation occurs on the basis of the equivalents of the ligand and time of the reaction. Ligand ratio tuned the nature of the complex as neutral and ionic behavior. All the complexes were characterized by spectroscopic and crystallographic studies, which revealed that complexes are formed by preferential binding through the neutral nitrogen of the pyrazole ligand rather than the protic nitrogen. In all these complexes deprotonation of the protic nitrogen does not occur unlike the other complexes containing
pyrazole derivatives. These complexes did not show any biological activities such as antibacterial or anti-fungal studies.
Half-sandwich d6 metal complexes have emerged as versatile intermediates in the organic chemistry synthesis due to the availability of three labile coordinate sites:
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