The Effect of Electron-withdrawing Group Functionalization on Antibacterial and Catalytic Activity of Palladium(II) Complexes

Abstract

The design, synthesis, and structural characterization of two new palladium complexes based on Schiff base ligands is reported; $[Pd(L1)_2]$ (1) and $[Pd(L2)_2]$ (2), [HL1 = 2-((E)-(2,6-diethylphenylimino)methyl)-4,6-dibromophenol, L2 = (E)-N-benzylidene-2,6-diethylbenzenamine], which are obtained by functionalizing Schiff base ligands with or without electron-withdrawing groups. Both compounds are mononuclear structures. Comparisons are made to the compounds 1 and 2 to analyze and understand the effect of electron-withdrawing groups. Antibacterial activity studies indicate the electron-withdrawing groups on Schiff base ligands enhance antibacterial activity. Catalytic activity, however, is reduced due to the enhanced steric-hindrance of the electron-withdrawing groups. Electronic absorption and emission properties of HL1, L2, 1 and 2 are also reported.

Introduction

Schiff bases are important compounds due to their wide range of biological activities,1 and as ligands in conjunction with transition metals. These transition metal-based compounds display diverse structural features and in some instances exhibit interesting reactivities, bacteriostasis and photoluminescence.2-6 Pd(II) complexes involving Schiff base ligands have received increasing recognition over the last decade due to their superior functional properties and potential applications, i.e. catalysis, antibacterial activity, luminescence.7-9 Guo et al. reported three Pd(II) complexes containing Schiff base ligands, which show moderate catalytic activity in the Heck coupling reaction of bromobenzene with acrylic acid.10 Ma et al. successfully synthesized a Pd(II) complex based on a fluorine-containing Schiff base ligand, which shows superior biological activity compared to Schiff base ligand without fluorine and exhibits photoluminescence in the solid state at room temperature.11 It has been found that Schiff base ligands with electron-withdrawing substituents such as –Cl, −Br, or –I had greater anti- Candida activity than ligands with electron-donating substituents.12 However, work on the effect of electron-withdrawing groups on antibacterial and catalytic activity in palladium(II) complexes is very scarce. Substituents with electron-withdrawing Schiff bases should enhance the antimicrobial activities, but reduce catalytic activity due to the enhanced steric-hindrance. To investigate this point further, HL1 with bromine and hydroxyl groups, and L2 with no electron-withdrawing groups were designed synthesized and their palladium(II) complexes obtained. Electronic absorption and emission properties of HL1, L2, 1 and 2 are also investigated.

 

Experimental

General Materials and Methods. All chemicals were commercially available and used as received without further purification. Elemental analyses for C, H, and N were carried out using a Vario EL III Elemental Analyzer. Infrared spectra were recorded (4000-400 cm−1) as KBr disks on a Shimadzu IR-440 spectrometer. Thermogravimetric analyses (TGA) were performed on an automatic simultaneous thermal analyzer (DTG-60, Shimadzu) under a flow of N2 at a heating rate of 10 °C/min between ambient temperature and 800 °C. Powder XRD investigations were carried out on a Bruker AXS D8-Advance diffractometer at 40 kV and 40 mA with Cu-Kα (λ = 1.5406 Å) radiation. Luminescence spectra and lifetimes for crystalline samples were recorded at room temperature on an Edinburgh FLS920 phosphorimeter. Nuclear Magnetic Resonance spectra were recorded on a Bruker Avance 400 MHz spectrometer. 1H-NMR chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl3, δ = 7.26). Data are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constants (Hz), integration, and assignment. 13C-NMR spectra were collected on a 100 MHz spectrometer with complete proton decoupling. Chemical shifts were reported in ppm from the tetramethylsilane (TMS) with the solvent resonance as internal standard (CDCl3, δ = 77.23). Melting points (uncorrected) were measured with a Mel-Temp apparatus.

Antibacterial Activity Tests. In vitro bacterial activities of the Schiff base ligands and their palladium complexes were tested using the paper disc diffusion method. The chosen strains were G(+) S. Aureus and B. cereus and Rhizopus and E. coli (which all provided by Depart of Food Science and Technology, Zhaoqing Univeristy) The liquid medium containing the bacterial subcultures was autoclaved for 20 min at 15 lb pressure before inoculation. The bacteria were cultured for 24 h at 35 °C in an incubator. Mueller Hinton broth was used for preparing basal media for the bioassay of the organisms. Nutrient agar was poured onto a Petri plate and allowed to solidify. The test compounds were dissolved in DMF and added dropwise to 10 mm diameter paper discs placed in the centre of the agar plates. The plates were then kept at 5 °C for 1 h and transferred to an incubator maintained at 35 °C. The width of the growth inhibition zone around the disc was measured after 24 h of incubation. Four replicates were taken for each treatment. In order to clarify any participating role of DMF in the biological screening, separate control studies were carried out with the solutions of DMF alone and they showed no activity against any bacterial strains. The bioassay results are shown in Table 4.

Catalytic Reactions. A mixture of 4-bromophenetole (1.0 mmol), phenylboronic acid (1.2 mmol), organic solvents (6 mL), bases (2.0 mmol) and 0.5 mol % of catalyst was stirred at 80 °C under air. After the reaction, the catalyst was separated by filtration. The filtrate was dried over Na2SO4 and filtered. The products were quantified by GC-MS analysis (Shimadzu GCMS-QP5050A equipped with a 0.25 mm × 30 m DB-WAX capillary column). The typical GC-MS analysis program was as follows: initial column temperature 100 °C, hold 2 min, ramp temperature to 280 °C at 15 °C/min, and hold for 5 min.

Preparation of Compounds.

HL1: The preparation of HL1 was carried out according to the reported procedures.13 Yield 5.6 g (70%). 1H NMR (400 MHz, CDCl3) δ 14.12 (s, 1H, OH), 8.24 (s, 1H, CHN), 7.26-7.79 (m, 5H, Ar-H), 2.53 (t, J = 5.0 Hz, 6H, CH3); 1.21 (m, 4H, -CH2-); 13C NMR (100 MHz, CDCl3) δ 165.2, 157.4, 146.4, 138.4, 134.2, 133.4, 126.6, 126.1, 120.2, 112.3, 110.4, 24.9, 14.9 (Fig. S2-S3). mp 84-86 °C. FTIR (KBr, cm−1): 3455(m), 2910(m), 1627(s), 1589(w), 1552(w), 1456(s), 1379(w), 1350(w), 1290(m), 1216(m), 1186(w), 1161(s), 1103(m), 1060(w), 1034(w), 987(w), 939(m), 865(w), 811 (m), 771(m), 741(w), 723(w), 689(s), 646(w), 551(w), 495 (w), 414(w).

L2: L2 has been reported14 and was prepared by the same procedure as for HL1 except that 3,5-dibromosalicylaldehyde was replaced by benzaldehyde. Yield 5.11 g (68%). mp 121-123 °C. FTIR (KBr, cm−1): 3440(s), 3055(w), 2965(m), 1614(s), 1585(s), 1554(w), 1460(s), 1399(w), 1380(s), 1274 (w), 1255(m), 1190(s), 1139(m), 1101(s), 1054(s), 983(w), 960(w), 861(vs), 832(m), 792(m), 762(w), 723(s), 681(w), 570(w), 451(m), 428(m).

[Pd(L1)2] (1): Pd(C2H3O2)2 (0.112 g, 0.5 mmol) was dissolved in methanol (15 mL). HL1 (0.411 g, 1 mmol) was added and the mixture stirred at room temperature for 2 h under an anhydrous atmosphere. The resulting mixture was filtered under reduced pressure. The collected solid was washed with diethyl ether and dried in air to give yellow crystals, that were purified by recrystallization from methylene chloride (10 mL) and hexane (10 mL). Yield 0.335 g (69%). Anal. For C34H32Br4N2O2Pd (%): Calcd. C 44.0, H 3.5, N 3.0; Found C 44.7, H 3.1, N 3.4. FTIR (KBr, cm−1): 3442(s), 2915(m), 2881(w), 1606(s), 1580(s), 1502(s), 1460 (s), 1453(m), 1388(w), 1362(w), 1310(w), 1295(w), 1253(w), 1230(w), 1202(w), 1178(w), 1115(m), 1054(w), 1030(w), 1001(w), 925(w), 916(w), 879(m), 818(m), 793(m), 759(s), 705(w), 669(w), 634(w), 573(w), 505(w), 488(w), 437(w), 415(w).

[Pd(L2)2] (2): Complex 2 was prepared by the same procedure as 1 except that HL1 was replaced with L2. Yield 0.31 g (82%). Anal. For C34H36Cl2N2Pd2 (%): Calcd. C 53.9, H 4.8, N 3.7; Found C 53.3, H 5.2, N 3.4. FTIR (KBr, cm−1): 3465(s), 2975(m), 2930(s), 1602(s), 1589(m), 1532(s), 1473 (s), 1447(s), 1384(m), 1376(m), 1263(w), 1223(w), 1188(m), 1165(w), 1121(m), 1026(w), 993(w), 965(w), 935(w), 903 (w), 847(m), 752(s), 691(s), 645(w), 620(w), 594(w), 565 (m), 490(s), 472(s), 424(w), 404(w).

X-ray Crystallography. X-ray diffraction for complexes 1 and 2 were performed on a Bruker Smart Apex II CCD diffractometer operating at 50 kV and 30 mA using MoKα radiation (λ = 0.71073 Å) at room temperature. Data collection and reduction were performed using the APEX II software. 15 Multi-scan absorption corrections were applied for all the data sets within the APEX II program.15 Both structures were solved by direct methods and refined by leastsquares against F2 using the SHELXTL program package.16 All non-hydrogen atoms were refined with anisotropic dis-placement parameters. Hydrogen atoms attached to carbon were placed in geometrically idealized positions and refined using a riding model. Crystallographic data for 1 and 2 are listed in Table 1. Selected bond lengths and angles for the compounds are given in Table 2. H-bonding parameters for 1-2 are given in Table 3.

Table 1.aR1 = Σ(||Fo| − |Fc ||)/Σ|Fo|. bwR2 = [Σw(Fo 2 – Fc 2)2/Σw(Fo)2]1/2, where w = 1/[σ2(Fo 2)+(aP)2+bP] and P = (Fo 2+2Fc 2)/3

Table 2.Selected bond length and angles of 1-2

Table 3.Symmetry code: i: x,1.5−y, 0.5+z.

 

Results and Discussion

Structure Description of 1. Complex 1 crystallizes in the monoclinic space group P21/c and contains one Pd(II) ion and two crystallographically independent L1 ligands, as shown in Figure 1(a). In this complex, each Schiff base ligand (L1) is bonded to the Pd(II) centre through nitrogen and oxygen atoms, providing two equivalent six-membered N-Pd-O-C-chelate rings. The geometry at the Pd(II) center in 1 is square planar, with the two cyclometalated ligands in a trans arrangement. The Pd-O and Pd-N distances are 1.980(5) and 2.014(6) Å, similar to those seen in related complexes.17 In the six-membered chelate rings, the six atoms (Pd1, O1, C2, C1, C7, N1) are essentially planar. The planes of the two phenyl rings are inclined by 87.24(2)° and 82.54(3)° to the PdN2O2 coordination plane, respectively. The bite angle [N1-Pd1-O1 = 92.98(2)°] is in good agreement with those found in a structurally related mononuclear complex with salicylaldiminato ligands as bridging ligands.18,19 The mononuclear molecules are linked into a 1D infinite chain by intermolecular C16-H16A···Br2 non-classical hydrogen bonds (Fig. 1(b)). Moreover, intramolecular C-H···N non-classical hydrogen bonds are also observed (Table 3).

Figure 1.(a) The molecular structure of 1 with 30% thermal ellipsoids (All H atoms are omitted for clarity); (b) View of 1D chain structure of 1 formed by C16-H16ABr2 hydrogen bonds in dashed lines.

Structure Description of 2. X-ray crystallography shows that complex 2 crystallizes in the triclinic space group P-1, and each Schiff base ligand (L2) is bonded to the di-μ- chloro-bridged unit through nitrogen and an aromatic carbon atom, provding two equivalent five-membered N-C-Pd-Cchelate rings. As shown in Figure 2(a), the geometry at the Pd(II) center in 2 is square planar, with the two cyclometalated ligands in a trans arrangement with respect to the Pd···Pd axis. The Pd1-C34 bond [1.973(4) Å] is shorter than the expected value of 2.08 Å based on the sum of the covalent radii of carbon and palladium, but consistent with those found for related complexes where partial multiple bond character of the Pd-C was assumed.20,21 The Pd1-N2 bond distance [2.031(3) Å] is in agreement with the sum of covalent radii for nitrogen and palladium,22 and is similar to values reported earlier.20,21 The lengths of the Pd-Cl bond trans to C [2.4576(10) Å] and the Pd-Cl bonds trans to N [2.3394(11) Å] reflect the different trans influences exerted by the phenyl carbon and nitrogen atoms. In the fivemembered chelate rings, the five atoms (Pd1, N2, C28, C29, and C34) are essentially planar. The bite angle [N2-Pd1-C34 = 80.88°] is in good agreement with those found in a structurally related μ-Cl dimer.21 The dinuclear molecules are connected into an infinite chain by intermolecular π···π stacking interactions between neighboring benzene rings (Cg1 and Cg2) of L2 ligands, with a centroid-to-centroid distance of 3.895(8) Å (Fig. 2(b)) [Cg1 and Cg2 are the centroid of the C12-C17 and C29-C34 rings, respectively]. Intramolecular C-H···Cl and C-H···N non-classical hydrogen bonds further stabilize the 1D chain (Table 3).

Figure 2.(a) The molecular structure of 2 with 30% thermal ellipsoids (All H atoms are omitted for clarity); (b) View of 1D chain structure in 2 with π···π stacking interactions in dashed lines.

Figure 3.PXRD patterns in complexes 1 and 2.

Powder X-ray Diffraction Analysis. In order to check the purity of complexes 1-2, bulk samples were measured by X-ray powder diffraction at room temperature, as shown in Figure 3. Although the experimental patterns have a few unindexed diffraction lines and some are slightly broadened in comparison with those simulated from the single-crystal data using Mercury, it is still resonable to suggest that the bulk synthesized materials and the crystals used for diffraction are homogeneous.

NMR and Infrared Spectra. The most characteristic signal in the 1H NMR spectrum of HL1 was due to the imine hydrogen singlet found at 8.24 ppm. The singlet for the phenolic proton of the ortho-hydroxy group was present at 14.12 ppm, the downfield shift resulting from the intramolecular hydrogen bonding to the imine nitrogen. In 13C NMR of the Schiff base ligand, the signal appeared in the region 110.4-157.4, and are assigned to aromatic carbon. The signal at 165.2, 24.9, and 14.9 ppm are due to C=N, CH3 and -CH2-, respectively.

FT-IR spectra of HL1, L2, 1 and 2 were recorded as KBr pellets (Fig. S1). In the IR spectrum, moderate bands at 2910 cm−1 for HL1, 3055, 2965 cm−1 for L2, 2915 cm−1 for 1 and 2975, 2930 cm−1 for 2, which are associated with the methyl (-CH3) or methylene (-CH2-) stretching vibrations. The features at 1627 cm−1 for HL1, 1614 cm−1 for L2, 1606 cm−1 for 1, and 1602 cm−1 for 2, may be assigned to the -CH=Nstretching vibrations. The absorption peaks of -CH=N- group in 1 and 2 are clearly blue-shifted against the related ligands, perhaps due to the conjugative effect between palladium ions and ligands.

Figure 4.TGA-DTA curves of complexes 1-2.

TG Analyses. The TG and DTA curves of 1-2 are shown in Figure 4. Complex 1 has thermal stability as no clean weight-loss step occurs below 230 °C. The weight-loss step above 230 °C corresponds to decomposition of the structure. Complex 2 shows a weight loss of 9.1% (100-200 °C), corresponding to the escape of two chlorine atoms (Calcd. 9.4%). Then, a sharp weight loss occurs above 250 °C due to decomposition of the structure.

Table 4.Antibacterial activieies of the ligands and complexes

Electronic Absorption and Emission Properties. The photophysical data for HL1, L2, 1 and 2 are summarized in Table 4. All of HL1, L2, 1 and 2 show low-energy absorp-tion bands at ca. 300-400 nm and higher energy bands at ca. 200-300 nm in DMF (Fig. 5). In the exploited wavelength domain from 200-450 nm, the B band of ligands HL1 and L2 is attributed to the π−π* transition are observed with absorption around 206, 254 nm for HL1 and 263 nm for L2. The absorption at 323 nm for HL1 and 329 nm for L2 corresponds to the K band of the charge transition between benzene rings and -C=N- group. The high energy absorption bands are assigned as intraligand (IL) transitions of complexes 1-2 based on their similarity to that of the free ligands HL1 (206, 254 nm) and L2 (263 nm). With reference to previous spectroscopic work on a series of cis-and trans-[M(PR3)2(X)(Y)] (M = Pd, Pt),23-25 [Pd2(P^P)2X4],26 [Pd(dbcpe)X2]27 and the close analogy of palladium(II) compounds with the platinum analogues and the nickel(II) congeners, the low energy absorption band at ca. 300-400 nm is tentatively assigned as a ligand-to-metal charge transfer [LMCT] transition in complexes 1-2. Moreover, the electronic absorption spectra of those complexes in the maximum absorption wavelength are red-shifted relative to the ligands due to the perturbation of the intraligand π−π* transition of the ligands by the palladium atoms.

Figure 5.UV-vis absorption spectra of 1 and 2 in DMF at 298 K.

Figure 6.Solid-state excitation and emission spectra of 1-2 at room temperature.

Figure 7.Luminescent lifetimes for 1 and 2.

As part of a continuing program dedicated to luminescent transition systems, the spectroscopic behavior of complexes 1-2 are presented. Both structures are non-emissive in DMF at room temperature, which is similar to the previous references. 26 Solid-state emission luminescence spectra of 1-2 at room temperature are shown in Figure 6. For 1, the emission spectrum shows a shoulder band at λmax = 508 nm and four bands at λmax = 565, 623, 767 nm. For 2, the emission spectrum shows one strong band at λmax = 615 nm, and three structureless bands at λmax = 699, 713, and 762 nm. Both the absorption and solid-state excitation spectra for 1-2 reveal the presence of low-energy ligand-field states in the 300-400 nm spectral region. The high-energy structures of 1 and 2 are assigned to a 3IL excited state.28 The luminescent lifetimes of solid 1 and 2 using an Edinburgh FLS S920 phosphori-meter with a 450 W xenon lamp as excitation source show lifetimes for 1 of τ1 = 92.10 ns, τ2 = 175.35 ns, and τ3 = 1602.20 ns at 565 nm, for 2 of τ1 = 75.52 ns, τ2 = 145.20 ns, τ3 = 1812.25 ns at 615 nm (Fig. 7).

Biological Activity. The susceptibility of certain strains of bacterium towards the ligands HL1-L2 and their metal complexes 1-2 were judged by measuring the size of their bactericidal diameters (vide supra). The results are given in Table 4. The effect against Staphilococcus aureus of ligands and complexes were found to be close to that of sodium penicillinate. All of the ligands and complexes showed inhibition diameters larger than sodium penicillinate against Bacillus cereus. Compared to HL1-L2 and 1-2 which show good activities, the penicillin is ineffective against Escherichia coli. However, similar to sodium penicillinate, the four tested samples showed no appreciable activity against Rhizopus. Moreover, we found that the complexes were more effective than the ligands. It is possible that the ligand may be activated by the metal ion.29 Moreover, HL1 and 1 show superior activities than L2 and 2, which maybe due to the introduction of electron-withdrawing groups in Schiff bases. El- Sherif reported a series of palladium complexes that show antibacterial activities against S. pyogenes and E. coli bacteria at different concentrations 1, 2.5, and 5 mg/mL in DMSO in which the activities were smaller in the complexes than in ligands.30 Also the results obtained for 1-2 and HL1-L2 show better antibacterial activities compared to the platinum(II) and palladium(II) complexes based on Schiff bases.31

Table 5.The effect of base and solvent on the complexes 1-2 catalyzed Suzuki reaction of 4-bromophenetole with phenylboronic acid

Suzuki Reaction Catalysis of 1-2. Pd(II) based complexes are well-known for their catalytic activities. The Suzuki reaction of 4-bromophenetole with phenylboronic acid catalyzed by 1-2 are reported here. The results reveal that the base and solvent for the Suzuki reaction greatly influence catalytic activity (Table 5). The reaction temperature has less effect on the catalytic activity of 1-2. Among six different organic solvents, DMF is found to be the best solvent for this catalytic system. In other organic solvents, for example, methanol, methanol/water (2:2), ethylene glycol, acetonitrile and toluene, relatively low yields of coupling products were obtained. Among five different bases investigated for these reactions, NaOAc was found to be the most effective (Table 5, entry 1); K2CO3, Na2CO3, CH3ONa, and NaOH were substantially less effective. KF failed to promote the reaction (Table 5, entry 13). Compared with other Pd(II) complexes based on Schiff base ligands, the catalytic activities of the present complexes for the Suzuki reaction proved to be highly effective.32 From table 5, 2 shows better catalytic activities than 1, which may be due to the electron-withdrawing groups of 1 enhancing the steric effect and thereby reducing the activity.

 

Conclusion

We have synthesized and structurally characterized two new palladium complexes based on Schiff base ligands with and without electron-withdrawing groups, [Pd(L1)2] (1) and [Pd(L2)2] (2), and carried out a systematic study to investigate and understand the effect of electron-withdrawing groups on the antibacterial activity and catalytic activity of HL1, L2, 1, 2 and 1, 2, respectively. The results reveal that the electron-withdrawing groups of Schiff base ligands will improve the antibacterial activity, but reduce the catalytic activity. Moreover, both 1 and 2 exhibit photoluminescence in the solid state at room temperature (τ1 = 92.10 ns, τ2 = 175.35 ns, and τ3 = 1602.20 ns at 565 nm for 1, τ1 = 75.52 ns, τ2 = 145.20 ns, τ3 = 1812.25 ns at 615 nm for 2), suggest utility as light-emitting luminescent materials.