Crystal Structure and Antimicrobial Properties of Rare Earths Aryl-acylhydrazone Complexes under Microwave Irradiation①

DI Yan-Qing LIU Yong-Liang DI You-Ying ZHOU Chun-Sheng REN You-Liang LI Mian-Qi

(College of Chemical Engineering and Modern Materials/Shaanxi Key Laboratory of Comprehensive Utilization of Tailings Resources,Shangluo University, Shangluo, Shaanxi 726000, China)

1 INTRODUCTION

Acylhydrazone compounds have been extensively applied in pesticides, medicine and other aspects by virtue of excellent bioactivity, strong coordination capacity and diversified coordination modes.Research finds that metabolites of acylhydrazones are all of low toxicity or no toxicity[1,2].In 2003, He S.Y.et al.[3]reported that salicylaldehyde salicylhydrazone and its complex had great inhibiting effect on phytophthora capsici, fusarium oxysporum vasinfectum, alternaria alternate, etc.In 2006, Song Fahui, Zhu Xinde et al.found through their researches that dual-salicylidene Schiff base of the ligand O-ethyl sulfo-thiophosphoric dihydrazide and its complex had certain activating effect on rice seedling cells when their concentration was within 10-5～10-6(mass fraction)[4].In 1988,Johari R.B.et al.reported that benzaldehyde salicylhydrazone showed antibacterial activity on aspergillus niger and aspergillus nidulans under 37 ℃ agar culturing environment, and bactericidal activity of the complex formed by these hydrazones and metals was stronger[5].In 2001, Easmon et al.reported that dual-ring hydrazones and 1-methyl-2-benzimidazole hydrazone had potential antitumor activity[6]; In 2002, Hofmann J.et al.stated that as one new kind of anticancer agents, 4-acetylpyridine-2?-benzothiazolyl hydrazone and 3-acetylisoquinolines-2?-benzothiazolyl hydrazone displayed extraordinary effects on resisting leukemia, melanoma, lung carcinoma and renal carcinoma[7].As a chemical element with physiological activity, rare earth has growth-facilitating and disease-resistant effects on crops and can enhance adaptability to adverse living environment and resistance against some plant diseases of crops by virtue of its bacterial inhibiting and sterilizing effects, anticorosion and mould-proof functions[8,9].In addition, a large quantity of experimental results indicate that rare earth complex belongs to substance with lower toxicity than many organically synthesized drugs or transition metal complex, and no rare earth is accumulated in vivo through oral administration or external application[10,11].

For research status of bioactivities of the above two constitutive elements-acylhydrazone and rare earth element, phase-transfer catalysis method under microwave radiation was used to synthesize 2-propanoic acid-4-methylbenzoyl hydrazone ligand which has been reported[12].But Schiff base rare earth complex Tb(PAMH)3obtained through coordination reaction between the ligand and TbCl3·6H2O is unreported.And the heat and luminescence of the complex have been studied.Also a preliminary study of in-vivo antibacterial activity of the ligand and complex was conducted.

2 EXPERIMENTAL

2.1 Instruments and reagents

NICOLET380 Fourier IR spectrometer (USA);NETSCHZ thermogravimetric analyzer (Germany);D/Max-3C X-ray diffractometer (Japan); RF960 fluorescence spectrophotometer (Shanghai);Cary5000 UV-invisible near-infrared spectrophotometer (USA); MAS-IIPlus microwave synthetic reaction workstation (Shanghai).

2.2 Synthetic method

2.2.1 Synthesis of ligand PAMH

Chemical reagents such as 4-methylbenzoyl hydrazine, pyruvic acid, absolute ethyl alcohol and acetic acid without any treatment used in the experiment were purchased from professional company.The synthetic methods refer to the reference[12], and the synthesis methods are optimized in the experiment.1.502 g (10 mmol) 4-methylbenzoyl hydrazine,1.232 g (14 mmol) pyruvic acid, 30 mL absolute ethyl alcohol and 2 drops of acetic acid were added into a 100 mL round-bottomed flask, and they were placed into a microwave reaction with condenser pipe.They were radiated under power 500 W at 75 ℃ for 30 min, and then the reaction flask was taken out.The reaction solution was placed in an abluent beaker which was sealed with plastic wrap,and yellow crystal was obtained after setting for several days.This synthetic method greatly shortened the reaction time when compared with the traditional Schiff base synthesis[13].For elemental analysis of C11H12O3N2, comparison of measured and theoretical values (unit: %) was as below: C, 60.03(60); H,5.52(5.45); O, 21.76(21.82); N, 12.69(12.73).m.p.:179.4～180.3 ℃.IR (KBr, cm-1): 1670(C=O),1530(C=N).

2.2.2 Synthesis of complex Tb(PAMH)3

0.4 mmol PAMH and 0.2 mmol TbCl3·6H2O were weighted and placed in a 250 mL three-necked flask,to which 36 mL mixed solution of methyl alcohol:acetone:water (3:2:4) was added.Then the flask was put under microwave radiation for 20 min under 500 W and 65 ℃.The reaction solution was filtered when still warm.Plastic wrap was used for sealing, and then colorless and transparent crystal was obtained after being kept for several days.For elemental analysis of C33H33N6O9Tb, comparison between measured and theoretical values is as below(unit: %): C, 48.52(48.47); H, 4.31(4.04); O,17.59(17.63); N, 10.32(10.28).m.p: ＞ 300 ℃.IR(KBr, cm-1): 1604 (C=O), 1450 (C=N).

2.2.3 Crystal structure determination

Diffraction intensities for the complex Tb(PAMH)3were collected on a D/Max-3C X diffractometer equipped with a graphite-monochromated MoKα radiation (λ = 0.71073 ?) using an ω-φ scan mode(1.71＜θ＜28.12°).Data reduction including the application of Lorentz and polarization effects (Lp)and absorption corrections was performed using the SADABS program[14].The structure was solved by direct methods and refined using subsequent Fourier difference techniques by full-matrix least-squares on F2using SHELXTL program package[15].Nonhydrogen atoms were refined anisotropically and hydrogen atoms were placed at the calculated positions and refined by a riding model.The final R =0.1252 and wR = 0.1265.The selected bond distances and bond angles are listed in Table 1.

Table 1. Selected Bond Distances (nm) and Bond Angles (o) for Complex Tb(PAMH)3

2.2.4 Antifungal assay

The antifungal activities in vitro of the synthetic ligand PAMH and complex Tb(PAMH)3against one plant pathogenic fungi (Fusarium solani) were assayed by the mycelium linear growth rate method as previously reported[16].The fungi maintained on potato dextrose agar (PDA) medium were subcultured for 48 h in Petri dishes for the pretreatment.The tested ligand PAMH and complex Tb(PAMH)3were separately dissolved in the mixed solvent of 1 mL acetone and 9 mL sterile water.1 mL related solution was added into 99 mL melted PDA agar at 50 °C.The final concentrations of each tested compound in the culture medium were respectively 0.05 and 0.1 mg/mL for the activity screening test,and the final concentration of acetone was 0.1% (v/v),which was proven to have no significant effect on the growth of tested fungi.Thiabendazole (50 μg/mL) in the culture medium containing 0.1% acetone (v/v)and 0.1% acetone in culture medium were used as a positive control and a blank control, respectively.When the medium in the plate was partially solidified, a 5 mm diameter disc of fungus cut from subcultured petri dishes was placed at the center of the semisolid medium.The dishes were kept in an incubator at 28 °C for 24, 48, 72 and 96 h.Each experiment was carried out in triplicate.The diameters (in mm) of inhibition zones were measured with a caliper in two different directions, and the growth antibacterial rates were calculated according to the following formula and expressed as means±S.D.

where d0is the diameter of the fungus cut, dc is the diameter of a fungal colony in the blank test, and ds is the diameter of a fungal colony in the compound-treated test.

2.3 Crystal structure of Tb(PAMH)3

Fig.1. Coordination environment of the Tb(PAMH)3

Single-crystal X-ray diffraction analysis reveals that complex Tb(PAMH)3is a zero-dimensional mononuclear structure.As shown in Fig.1, the asymmetric unit consists of one Tb(III) ion and three completely deprotonated PAMH ligands.The central Tb(III) ion is coordinated by three nitrogen atoms,three carbonyl oxygen atoms, and three carboxylate oxygen atoms from three PAMH ligands.Tb(III) ion is located in a nine-coordinated tricapped trigonal prism geometry, in which the three PAMH ligands are approximately perpendicular to each other.Each PAMH ligand offer two nitrogen atoms, three carbon atoms, and two oxygen atoms to construct two stable five-membered (Tb–N) edge-shared rings (Tb–N–N–C–O and Tb–N–C–C–O), which have nearly coplanar relationship with ligand PAMH benzene ring.Bond lengths of Tb–O and Tb–N fall in the ranges of 0.231(11)～0.2442(8) and 0.2541(8)～0.2548(10) nm, respectively.It’s obvious that the Tb–O bond is shorter than Tb–N, which indicates that Tb–O has stronger binding force.According to Lewis' acid-base theory, as a hard acid, rare earth ion owns small volume and low deformability and easily tends to bind with hard base to form stable compounds.The oxygen atoms in carbonyl and carboxyl groups are of high electronegativity and belong to hard base, whereas nitrogen atom in -NH2belongs to borderline base.So, bond length of Tb–O is shorter with greater stability[17].

Adjacent molecules are linked through intramolecular hydrogen bonds of N(3)–H(3)···O(3), N(2)–H(2)···O(9) and N(5)–H(5)···O(6) (listed in Table 2)and π-π stacking interactions to form a 3D supramolecular structure (Fig.2).

Fig.2. Packing diagram of Tb(PAMH)3

Table 2. Hydrogen Bonds in the Tb(PAMH)3 Complex

2.4 Properties of the ligand and complex

2.4.1 IR spectrogram analysis

IR analyses of the ligand PAMH and the complex Tb(PAMH)3were obtained on Fourier transform IF spectrometer, as shown in Table 3.The absorption peak of the ligand at 1,530 cm-1is attributed to the stretching vibration of C=N, which is weaker than that of the complex (1450 cm-1).This indicates that the N atom of the imino group in the complex participates in coordination to the metal cation.In the same situation, the absorption peak of the ligand at 1670 cm-1is attributed to the stretching vibration of C=O, weaker than the related one of the complex(1604 cm-1).Thus, it can be speculated that the carbonyl O atom in the complex also participated in coordination.Moreover, the absorption peak of the ligand at 3305 cm-1from the stretching vibration of N–H is smaller than the related one of the complex(3207 cm-1) probably because that hydrogen bonds are formed between adjacent molecules.

Table 3. Infrared Spectra Data for the Ligand and Complex

2.4.2 UV spectrometry

A Cary5000 UV-invisible near-infrared spectrophotometer was used to record the UV-vis spectra in the 200～400 nm range.The spectrophotometric titrations were performed on samples of ligand PAMH and complex Tb(PAMH)3at 298.0 ± 0.1 K.Ethyl acetate with a small quantity of dimethyl sulfoxide solution was taken as solvent and the resulting concentrations of the ligand and the complex were 1.0 mM.Absorbance data recorded in the wavelength interval from 260 to 360 nm were used for the calculations.As shown in Fig.3, UV absorption spectra of the ligand and the complex were determined within the scope of 270～380 nm.The absorption band of the ligand and Tb(PAMH)3in the range of 270～345 nm are π → π*and n → π*transition[18].The maximum wavelengths of the ligand and Tb(PAMH)3are 310 and 295 nm, respectively.Obviously, the maximum wavelength of the complex is 15 nm,which is blue-shifted compared to that of the ligand,probably resulting from the coordination bond formed by imine N in the ligand and metallic ions[19].

2.4.3 Fluorescent spectrometry

The emission spectra of the ligand PAMH and complex Tb(PAMH)3in their solid states were investigated at room temperature under the same conditions.The resulting concentrations of the ligand and the complex were about 1.0 mM, taking ethyl acetate with a small quantity of dimethyl sulfoxide solution as the solvent.As depicted in Fig.4, the ligand displays emission peak at 512 nm upon excitation at 361 nm, which can be attributed to the transition of p electrons of the aromatic rings.And the complex exhibits emission peak at 502 nm (λex=361 nm), leaving a blue shift of 10 nm which can be assigned to the ligand-to-metal charge transfer(LMCT) and stacking effect of the ligand[20].The bonds between the ligand and metallic ions effectively enhance the ligand rigidity[21,22], reducing energy loss brought by internal charge transfer of the ligand and effectively transferring the energy to the central ions.

Fig.3. Ultraviolet emission spectra of the ligand and the complex

2.4.4 Thermostability analysis

To study the stability of PAMH and Tb(PAMH)3,thermogravimetric analyses (TGA) of them were performed and the TGA curves are shown in Fig.5.For the ligand, the first weight loss within 25～175 ℃ can be attributed to the loss of free water molecules (obsd.: 8.2%).Above this temperature,the whole structure began to collapse with the residual weight of 2.7% at 700 ℃.For Tb(PAMH)3,

Fig.4. Fluorescent emission spectra of the ligand and the complex

2.5 Researches on antibacterial activities of the ligand and complex

Figs.6 and 7 show the antibacterial results of the ligand and the complex with different concentrations in different time periods.It’s obvious that both of the ligand and the complex have significantly inhibitory effect on fusarium solani.Under the fixed incubation time, the greater the concentration of the ligand and the complex, the higher their antibacterial rates;the framework began to collapse from 330 ℃,suggesting that the frameworks are thermally stable.The resulting residue of the complex remainS as Tb2O3(calcd.: 22.4%, found: 23.2%) after the complete decomposition of the organic ligands.under the fixed concentration, the antibacterial rates of the ligand and the complex are the highest when cultured for 72 h, which might be related to the metabolic cycle of bacterial strain[23,24].Under the same conditions, antibacterial activity of rare earth complex was far greater than that of the ligand,probably because antibacterial activity of rare earth complex was enhanced through synergistic effect between rare-earth salt and ligand.

Fig.5. TGA curves of PAMH and Tb(PAMH)3

3 CONCLUSION

In summary, one new compound was successfully synthesized from the self-assembly of the ligand PAMH and Tb(III) metal salt under hydrothermal conditions.It is notable that the complex owns favorable thermo stability and antibacterial activity,providing theoretical foundation for researching acylhydrazone rare earth complex in pesticides.

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