Chinese Journal of Chemistry, 2009, 27, 1312—1316 Full Paper

* E-mail: wdjizp@126.com; Tel.: 0086-027-87218274; Fax: 0086-027-87647617 Received December 19, 2008; revised February 23, 2009; accepted March 25, 2009. Project supported by the National Natural Science Foundation of China (No. 20171035).

© 2009 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis, Crystal Structure and Bioactivities of a Novel Propeller Shaped Manganese Complex with the

Ligand N'-Benzylidenesalicylhydrazide

LI, Bo(李波) SUN, Xuzhuo(孙旭镯) CHENG, Gongzhen(程功臻) JI, Zhenping*(季振平)

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China

A new propeller shaped mononuclear manganese(III) complex of the general formula: [MnL3(H2O)], where HL is N'-benzylidenesalicylhydrazide, was synthesized and characterized. The crystal structure of the title compound was characterized by X-ray single crystal diffractometry, which belongs to a triclinic system with space group P-1, cell dimensions of a＝11.6411 Å, b＝12.728 Å, c＝16.346 Å, α＝110.357°, β＝96.555°, γ＝108.996°, V＝2075.2 Å3, Z＝2 and Dcalc＝1.265 g/cm3. In this complex, the metal ion is in an octahedral coordination environment, en-forcing the stereochemistry of the ligands as a propeller configuration. Antibacterial screening data indicate that the complex has stronger antibacterial activity against the tested microorganisms than the ligand.

Keywords manganese complex, salicylhydrazide, crystal structure, antibacterial activity

Introduction

Ttransition metal complexes of Schiff base ligands containing carboxylate groups are of great interest in chemistry, as these ligands offer opportunities for in-ducing substrate chirality, tuning the metal-centered electronic factor, and enhancing the solubility and sta-bility of either homogeneous or heterogeneous cata-lysts.1-9 Also, since the past few years the Schiff base complexes have become increasingly important as bio-chemical, analytical and antimicrobial reagents.10 A great deal of work has been performed on the synthesis and characterization of transition metal compounds with these Schiff base ligands, not only due to their novel structural features caused by the chelating capability of these ligands but also in view of their pharmacological and antitumour activity.11-13 In particular, complexes with Schiff bases derived from amino acids14-16 and ONO and NNO tridentate dianionic Schiff bases have been widely reported.17-20 This type of ligand typically acts as a multidentate planar chelating agent coordi- nating through the phenolic and amide oxygens and imine nitrogen.

As a continuation of our previous work dealing with the study of the interaction of transition metal ions with Schiff bases,21,22 we report here the synthesis and char-acterization of a new propeller shaped complex 2 from the combination of the manganese ion and three ligands N'-benzylidenesalicylhydrazide (1) (Scheme 1). The structure of the complex and the antibacterial activities are discussed. The complex has stronger antibacterial

activity against the gram-positive bacteria.

Scheme 1 N'-Benzylidenesalicylhydrazide (1) and its binding site in the complex

Experimental

General procedure

All reagents were purchased commercially and used without further purification. Elemental analysis was carried out on a Perkin-Elmer-240C element analyzer. Infrared spectra were measured on a Perkin-Elmer FT-IR 2000 spectrometer as KBr pellets in 4000—400 cm－1 region. 1H NMR spectra were recorded on a Var-ian Mercury-vx 300 MHz spectrometer.

Synthesis of the ligand N'-benzylidenesalicylhy- drazide (1)

To an ethanolic solution (20 mL) of salicylhydrazide (1.52 g, 10 mmol) was added an aqueous solution of benzylaldehyde (98%) and the mixture was stirred for 2 h. The resulting white precipitate was filtered and rinsed with ethanol (1.90 g, 79% yield). 1H NMR (DMSO-d6, 300 MHz) δ: 12.28 (s, 1H, NH), 10.81 (s, 1H, OH), 8.10 (s, 1H, HC＝N), 7.82—6.94 (m, 9H, aromatic); IR (KBr) ν: 3265, 3076, 1682, 1644, 1549, 1331, 1229, 1160

Manganese complex Chin. J. Chem., 2009 Vol. 27 No. 7 1313

© 2009 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

cm－1. Anal. calcd for C14H12N2O2: C 70.00, H 5.00, N 11.67; found C 69.92, H 4.55, N 11.33.

Synthesis of the title complex [MnL3(H2O)] (2)

0.74g (1.0 mmol) of N'-benzylidenesalicylhydrazide was dissolved in 20 mL of DMF and 0.245 g (1.0 mmol) of manganese(II) acetate tetrahydrate was dissolved in 10 mL of DMF in another flask. The two solutions were mixed, stirred and then filtered. Dark brown rectangular crystals were obtained after slow evaporation. IR (KBr) ν: 3424, 3057, 1602, 1533, 1510, 1183, 454 cm－1. Anal. calcd for C42H35MnN6O7: C 63.80, H 4.43, N 10.63; found C 63.74, H 4.05, N 10.56.

Crystal structure determination

A single crystal of compound 2 suitable for X-ray crystallography diffraction was mounted in a glass cap-illary with mother liquor to prevent the loss of the structural solvent during X-ray diffraction data collec-tion. The capillary was transferred to a Bruker Smart Ape CCD area detector diffractometer at 293 K. The intensities were collected using graphite monochroma-tized Mo Kα radiation (λ＝0.71073 Å). A summary of data collection parameters is given in Table 1. A total of 10496 reflections were collected (7206 independent reflections, Rint＝0.0196) in the range of 2.33°≤θ≤

14.45º using phi and omega scan modes and 6107 were unique with I＞2σ(I). The structure was solved by direct methods using program SHELXTL and refined by full-matrix least-squares calculations with SHELXTL. All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were placed in the geometrical po-sitions and refined with a riding mode. A summary of the crystal data, experimental details and refinement results are listed in Table 1.

Antibacterial activities

The antimicrobial activities of the complexes were assessed by their ability to inhibit the growth of Staphy-lococcus aureus, Escherichia coli, Bacillus subtilis and Proteus vulgaris in Mueller-Hinton broth medium. The minimum inhibitory concentrations in μg/mL against the four bacterial species were measured. The bacterial concentration was 5×105

—5×106 cfu/mL and concen-trations of 1600, 800, 400, 200, 100, 50 and 25 μg/mL of the complexes in DMF were used. The solvent showed no antimicrobial action.

Results and discussion

IR spectrum

The IR spectrum of the complex in the region 4000—400 cm－1 was analyzed in comparison with that of the free ligand, finding that the absorption peak at 1644 cm－1 corresponding to ν(C＝N) of the uncom-plexed salicylhydrazone shifts to ca. 1600 cm－1 upon complexation indicating the azomethine nitrogen

Table 1 Crystallographic data for compound 2

Empirical formula C42H35MnN6O7

CCDC deposit No. 273488

Molecular weight 790.70

Crystal system Triclinic

Space group P-1

a 11.6411(18) Å

b c

12.728(2) Å 16.346(3) Å

α β γ

110.357(3)° 96.555(3)° 108.996(3)°

V 2075.2(6) Å3

Z 2

Dcalc 1.265 g•cm－3

θ range for data collection 2.33°≤θ≤14.45º

Reflections collected 10496

Independent reflections 7206

Final R indices [I＞2σ(I)] R1＝0.0666, wR2＝0.1538

R indices (all data) R1＝0.0823, wR2＝0.1610

Largest diff. peak and hole 0.23 and －0.38 e/Å3

GOF on F2 1.075

R＝Σ||Fo|－|Fc||/Σ|Fo|. wR＝[Σw(Fo2－Fc

2)2/Σw(Fo2)2]1/2.

coordination. Further proof for the complexation for the imino-group bond nitrogen is obtained from the ap-pearance of a new band at 454 cm－1, which was as-signed to the ν(Mn—N) for the complex. The increase in ν(N—N) in the spectrum of the complex from 1160 to 1183 cm－1, is due to the increase in the double band character offsetting the loss of electron density via do-nation to metal and is a further confirmation of coordi-nation of the ligand through the azomethine nitrogen atom. The IR spectra show a sharp band at 1533 cm－1, which indicates the newly formed uncomplexed N＝C by enolisation, confirming the coordination of hydra-zone takes place in the form of the enol rather than the keto form. The complex and the ligand show an IR band at ca. 3400 cm－1, which is reasonably attributable to the water molecule. The vibration attributed to the ν(N—H) was observed at 3265 cm－1 for the free ligand, which disappeared in the complex spectra indicating the de-protonation of the N—H proton and coordination via the enol oxygen. The OH group in the aromatic ring re-mains uncomplexed as indicated by a band at 3057 cm－1 in the complex. All of the data confirm the fact that there is a conjugate chelate ring formed by ligand enolization in the complex, which is consistent with the result of the crystal structure of the complex.

Crystal structure

The crystal structure of the manganese complex is shown in Figure 1 and the selected bond lengths and angles are given in Table 2.

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Table 2 Selected bond lengths (Å) and angles (°) of the title compound

Mn(1)—O(5) 1.876(2) N(3)—N(4) 1.380(4)

Mn(1)—O(3) 1.882(2) N(5)—N(6) 1.381(4)

Mn(1)—O(1) 1.897(3) N(4)—C(22) 1.273(5)

Mn(1)—N(6) 1.196(3) N(3)—C(21) 1.358(4)

Mn(1)—N(2) 1.918(3) C(2)—O(2) 1.398(4)

Mn(1)—N(4) 1.928(3) C(7)—O(1) 1.302(4)

N(1)—N(2) 1.363(4)

O(5)-Mn(1)-O(3) 89.83(10) N(5)-N(6)-Mn(1) 112.9(2)

O(5)-Mn(1)-O(1) 178.64(11) C(36)-N(6)-Mn(1) 126.1(3)

O(3)-Mn(1)-O(1) 91.35(11) N(3)-N(4)-Mn(1) 111.0(2)

O(5)-Mn(1)-N(6) 82.99(11) C(35)-N(5)-N(6) 110.7(3)

O(3)-Mn(1)-N(6) 172.69(12) C(36)-N(6)-N(5) 120.7(3)

O(1)-Mn(1)-N(6) 95.79(12) C(8)-N(2)-N(1) 121.7(3)

O(5)-Mn(1)-N(2) 96.38(12) C(7)-N(1)-N(2) 110.8(3)

O(3)-Mn(1)-N(2) 89.31(11) N(1)-N(2)-Mn(1) 113.1(2)

O(1)-Mn(1)-N(2) 83.00(11) C(1)-C(7)-Mn(1) 161.6(2)

N(6)-Mn(1)-N(2) 90.00(12) C(22)-N(4)-Mn(1) 128.3(3)

O(5)-Mn(1)-N(4) 93.21(12) C(8)-N(2)-Mn(1) 125.0(3)

O(3)-Mn(1)-N(4) 83.92(11) O(1)-C(7)-N(1) 123.3(3)

O(1)-Mn(1)-N(4) 87.56(12) C(21)-N(3)-N(4) 112.7(3)

N(6)-Mn(1)-N(4) 97.93(12) N(1)-C(7)-C(1) 117.0(3)

N(2)-Mn(1)-N(4) 168.25(12) C(22)-N(4)-N(3) 120.6(3)

The structure reveals that the manganese in the mononuclear complex is six coordinated and has an ap-proximate octahedron geometry. The three salicylhy-drazone ligands are coordinated to the manganese ion as bidentate chelating agents via the imido nitrogen N(2) and the carbonyl oxygen O(1) of the hydrazone (Scheme 1). Thus three five chelating rings are formed. The datum for C(7)—O(1) [1.302(4) Å] bond length shows that the carbonyl inclines to a monobond in the complex, compared with the present transition metal complexes.23-25 The C(7)—N(1) [1.324(4) Å] is similar to a double bond, confirmed by the bond length of C(8)—N(2) [1.322(4) Å]. All these demonstrate that the oxygen [O(1)] of carbonyl group takes part in coordi- nation by the enolic form.

The most striking feature of the present system is that the central manganese atom is linked by three ligands and enforces the three ligands to take a propeller configuration. Most structures of the reported mononu-clear transition metal hydrazone complexes are one metal atom coordinated with one or two ligands,23-27 while the crystal structure of one metal atom with three hydrazone ligands has never been reported. The charge balance of the complex in the crystal structure suggests that the oxidation state of the manganese ion is ＋3.28 The Mn—O(1) and Mn—O(5) bond lengths are 1.897(3) and 1.876(2) Å. The Mn—N(2) and Mn—N(4) bond lengths are 1.918(3) and 1.928(3) Å, which are similar

to those of the six-coordinated manganese complexes of related ligands.29 The Mn—O(3) and Mn—N(6) bond lengths are 1.882(2) and 1.917 Å. The length of N(2)-Mn-N(4) is a little longer (0.05 Å) than the aver-age of O(1)-Mn-O(5) and O(3)-Mn-N(6). The differ-ence in bond lengths can be attributed to the difference between the ion radii of nitrogen and oxygen. The four equatorial atoms are coplanar showing a slight distor-tion from square geometry indicated by the O(1)-Mn(1)-O(5) and O(3)-Mn(1)-N(6) bond angles [178.64(11)° and 172.69(12)°]. The bond angles O(1)-Mn(1)-O(3), O(3)-Mn(1)-O(5) and N(2)-Mn(1)- N(6) [91.35(11)°, 89.83(10)° and 90.00(12)°] indicate the tiny distortion from the perfect octahedron geometry. One of the reasons for the deviation from an ideal stereochemistry is the restricted bite angle imposed by the asymmetry of the ligands. The water molecule standing as intramolecular solvent does not bond to the manganese.

Figure 1 Molecular structure of compound 2. H atoms and water molecules are omitted for clarity.

An interesting feature in the packing diagrams of the complex is the regularly aromatic π-π stacking interac-tions between the phenyl groups of two ligands (Figure 2). The center-to-center distance of the phenyl groups is approximately 3.7 Å, with the shortest C—C distance of 3.321 Å observed.30,31

Antibacterial activities

Data on antibacterial activity of the ligand and com-plex against S. aureus, E. coli, B. subtilis and P. vul-garis are listed in Table 3. As can be clearly seen from the table, the free ligand showes little activity against both the Gram positive and Gram negative bacteria, while the complex has stronger antimicrobial activities than the ligand at MIC with a range of 100—200 μg/mL. Comparing the activities against these four kinds of

Manganese complex Chin. J. Chem., 2009 Vol. 27 No. 7 1315

© 2009 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Figure 2 π-π stacking interactions between the phenyl groups of two ligands. H atoms and water molecules are omitted for clarity.

bacteria, the manganese complex was found to be the most active against S. aureus and B. Subtilis. The results in this study indicate that the complex has strong activi-ties against the gram-positive than the gram-negative bacteria as expected.21 It has been found that the metal salts and the ligand do not exhibit antibacterial activities in the concentration range used to assay the activities of the complex in this work. When the antibacterial activ-ity of the metal complexes is investigated, the following principal factors should be considered: (i) the chelate effect of the ligands; (ii) the total charge of the complex; (iii) the nature of the N-donor ligands; (iv) the existence and the nature of the ion neutralizing the ionic complex and (v) the nuclearity of the metal center in the com-plex.32 In this work, the first factor is the main factor.

Until now, only a few mononuclear transition metal complexes and limited polynuclear complexes have been tested as antibacterial agents. Compared to the linear trinuclear complex [Ni3(H2O)2(DMA)2(acbshz)2]• 2DMF with high MIC value (400—800 μg/mL),22 the MIC of compound 2 is much lower. Compared to the tetranuclear nickel(II) complex ([12-MCNi(II)N(Hshi)2(pko) 2

- 4](NNN)2(DMF)(CH3OH)) with the low MIC value (12—25 μg/mL),33 the MIC value of compound 2 is much higher. Based on these data, it is still not ready to corre-late the nuclear and ligand numbers to the antibacterial activity. Although it is risky to correlate the bioactivity of these compounds to the structural features, we can stress that the ratio of the metal to the ligands of these complexes is important. The work to prepare more mul-tinuclear complexes and correlate the relationship be-tween the nuclearity and antibacterial activity is in pro-gress in our laboratory.

Table 3 Minimum inhibitory concentration (MIC) of the ligand and the complex in μg/mL

Microorganism Ligand Complex

S. aureus (Gram＋) 800 100

E. coli (Gram－) 1600 200

B. subtilis (Gram＋) 800 100

P. vulgaris (Gram－) ＞1600 200

Supplementary materials

Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, by a CCDC reference number 273488 for compound 2. Copies of this information may be ob-tained free of charge from The Director, CCDC, 12 Un-ion Road, Cambridge CB2 1EZ, UK (fax:＋44-1223- 336-033; email: deposit@ccdc.cam.ac.uk or www: http://www.ccdc. cam.ac.uk).

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