Synthesis, Structureand Characterization of a Biologically Active Compound Based on 5-Nitrosalicylaldehyde Schiff Base①

TIAN Ai-Qin CHEN Jun-Ling FENG Xun WANG Wei-Zhou WANG Li-Ya,

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Synthesis, Structureand Characterization of a Biologically Active Compound Based on 5-Nitrosalicylaldehyde Schiff Base①

TIAN Ai-Qina, bCHEN Jun-LingcFENG XunbWANG Wei-ZhoubWANG Li-Yab, c②

a(471002)b(471022)c(473601)

A new Schiff base compound ((NSBSH)2bipy·3H2O) based on 5-nitrosalicylal 4-methyl benzene-sulfonohydrazide (abbreviated as NSBSH), formulated as C38H40N8O13S2,has been synthesized by the condensation of 5-nitrosalicylaldehyde and 4-methylbenzenesulfonohy- drazide, and structurally characterized by X-ray single-crystal diffraction analysis, elemental analysis and IR spectrum. It crystallizes in monoclinic system, space group2/with= 13.7992(16),= 7.1410(8),= 21.403(2) ?,= 95.5660(10)oand= 2099.1(4) ?3. X-ray analysis reveals that there are obviousstacking interactions between two adjacent aromatic ring planes. The intermolecular hydrogen bonding interactions connect the adjacent Schiff base units into a binuclear unit, and further propagate these moieties into a two-dimensional (2D) supramolecular network. The title compound displays strong photoluminescence in the liquid state as well as high thermal stability. The experiment also shows that it has a good antibacterial activity in vitroantibacterial activity against.

5-nitrosalicylaldehyde, X-ray single-crystal, photoluminescence,density-functional theory calculations

1 INTRODUCTION

In recent years, the complexes of salicylaldehyde Schiff base have received considerable attention due to the interest in the field of biology and chemistry[1]. Exploration of various synthetic methods and studies on their structure activity relationship and applica- tion will inevitably drive the process, among which some of the compounds synthesized from it are proven to possess biological activities, such as anticancer, antibacterial effects and interaction with DNA[2]. So far, a great many complexes of salicylal- dehyde Schiff base have been documented, however, the complexes incorporating electron-withdrawing groups like nitro group are seldom reported[3]. In this contribution, a new Schiff base compound based on 5-nitrosalicylaldehyde and 4-methy benzenesulfono- hydrazide has been obtained. The compound couldnot only restrain bacteria but also exhibit strong photoluminescence in the liquid state.

2 EXPERIMENTAL

2.1 Reagents and instruments

All commercially available solvents and chemi- cals were of analytical grade. Elemental analysis (C, H and N) was performed on a Perkin-Elmer 2400 elemental analyzer. IR spectrum was recorded in the range of 400～4000 cm-1using a VECTOR-22 spectrometer. Luminescence spectrum of the title compound in a 1 cm quartz spectrophotometer fluorescence cell (Starna) in methanol was run on a F4500 fluorescence spectrophotometer. The thermal stability experiment was performed on samples consisting of numerous single crystals of the title compoundunder N2atmosphere with a heating rate of 10 ℃ min?1. The density functional theory calculation was carried out at the M052X/6-31G (d) theory level using the Gaussian 09 suite of electronic structure programs[4].

2.2 Synthesis of the title compound

The mixture of Cd(OAC)2·3H2O (0.057 g, 0.2 mmol) and 4,4?-bipyridine (0.031 g, 0.2 mmol) was refluxed in anhydrous methanol (10 mL) at 60 ℃. After stirring for 2.0 h in air, the mixture was cooled to 50 ℃, followed by adding a methanol solution (10 mL) containing 5-nitrosalicylaldehyde (0.067 g, 0.4 mmol) and 4-methylbenzenesulfonohydrazide (0.075 g, 0.4 mmol) simultaneously. Then the solution was vigorously stirred for a further 2.0 h, and the pH value was adjusted to 7.2 with triethylamine. Afterwards, the mixture was cooled down to room temperature naturally and filtered. After one week, colorless crystals in good quality were obtained from the mother solutionand washed with distilled water, then dried in air. Yield: 0.102 g (76%) on the basis of 5-nitrosalicylaldehyde. Elemental analysis: Calcd. for C38H40N8O13S2: C, 51.81; H, 4.58; N, 12.72; S, 7.28%. Found: C, 51.72; H, 4.46; N, 12.51, S, 7.25%. IR (KBr pellet, cm-1): 3450br,3260s, 2923s, 2014m, 1652s, 1554s, 1393s, 1192s, 792m, 817s, 725s, 572s.

2.3 X-ray structure determination

X-ray single-crystal diffraction data of the title compound (0.41mm × 0.38mm × 0.32mm)were collected on a Bruker SMARTAPEX II CCD dif- fractometer equipped with a graphite-monochro- mated Moradiation (= 0.71073 ?) at room temperature in the range of 2.53≤≤25.50o with index ranges of-16≤≤16,-8≤≤8 and-25≤≤25.A total of 15307 reflections were collected, of which 3910 were independent (int= 0.0246) and 769 with> 2() were observed and used for structure refinements. The structure was solved by direct methods and successive Fourier difference synthesis (SHELXS-97)[5], and refined using the full-matrix least-squares method on2with aniso- tropic thermal parameters for all non-hydrogen atoms (SHELXL-97)[6]. An empirical absorption correction was applied using the SADABS program. The hydrogen atoms of organic compound were placed in the calculated positions geometrically and refined using a riding on attached atoms with isotropic thermal parameters 1.2 times those of their carrier atoms. Corrections forfactors were applied and all non-hydrogen atoms were refined with anisotropic thermal parameters. The final= 0.0356,= 0.0863 (= 1/[2(F2) + (0.04162) + 0.7021], where= (F2+ 2F2)/3), (D)max= 0.204and (D)mix=-0.301 e/?3. Moreover, the selected bond lengths and bond angles are listed in Table 1.

3 RESULTS AND DISCUSSION

3.1 Synthesis

Our initial attempt was to employ cadmium acetate to catalyze the reaction with 5-nitrosalicylaldehyde and 4-methyl-benzene-sulfono hydrazideconden- sation and refluxing approachto obtain the cadmium complex. However, an organic compound rather than the target complex was afforded, during which the acetalization reaction took place between 5-nitro- salicylaldehyde and 4-methylbenzene sulfonohydra- zide to generate a Schiff basecompound, as given in Scheme 1. This may be due to the acidity of this reaction system leads to the deposition ofmetal complex[7]. Similar experiment reactions were per- formed out at the absence of cadmium acetate in the mixture, but the same compound could not be obtai- ned, which indicates that cadmium cation plays an important role in forming the Schiff base compound[8].

Scheme 1. Synthesis route of the title compound

Table 1. Selected Bond Lengths (?) and Bond Angles (°) for theTitle Complex

Symmetry transformations used to generate the equivalent atoms: #1: –,, –+1/2

3.2 Crystal structure description

-analysisthe title compound consists of three discrete fragments, a Schiff base and one 4,4?-bipyridine molecule as well as three crystallization water molecules. The pers- pective view of the title compoundwith atom labeling scheme is illustrated in Fig. 1. The Schiff base (NSBSH) is composed of two organic moieties, 4-methylbenzene-sulfonohydrazide and 5-nitrosa- licylaldehyde, connected by C=N linker. In the compound, the Schiff base displays a distorted “V” configuration, in which the torsion angle of N(2)–N(1)–S(1)–C(6)is 57.67°, and the dihedral angle between the two benzene rings is 85.99°, indicating they are nearly perpendicular to each other. Further- more, the dihedral angle between the two pyridine rings in 4,4?-bipyridine is 42.75°, which are much distorted. This confirmed that the free rotation of aromatic rings at different conformations in the flexible ligand, as the ligands based on the azo or sulfonylamino linkers of pyridine or benzene dicar- boxylate, has been observed in numerous ligation modes[9, 10]. The first benzene ring of C(9)–C(10)– C(11)–C(12)–C(13)–C(14) is nearly coplanar with the maximum deviation of 0.007 ? for C(13) and 0.007 ?for C(10). Another benzene ring of C(1)– C(2)–C(3)–C(4)–C(5)–C(6) is also nearly coplanar with the maximum deviation of 0.004 ? for C(1) above the mean plane, and 0.005 ? for C(4) above this mean plane. The average connecter O(3)–S(1) and N(1)–S(1) distances are respectively 1.4326(14) and 1.6289(17) ?, comparable to that of the com- plex containing thiophene carboxamide pyridine moieties[11, 12].The O(5) and O(6) atoms of the nitro group and O(8) atom of hydroxyl are almost coplanar, and the deviation out of the mean plane defined by the C(9)–C(10)–C(11)–C(12)–C(13)– C(14) benzene ring is less than 0.025 ?. This implies that the benzene is fairly rigid and retains its integrity when linked by the C=N double bonds. In the molecule, the bond lengths of C(3)–C(7), C(8)– C(9) and C(17)–C(17)#1 are found to be 1.506(3), 1.459(2) and 1.486(3) ?, respectively, which are also nearly equal to each other belonging to the typical single bond lengths[13].There are obvious hydrogen bonds between the O(1) atom from free water and O(8) of hydroxyl group, and this hydrogen bond connects adjacent NSBSH moieties into a dimer unit. Meanwhile, there is also strong hydrogen bond between the O(8) atom from hydroxyl group and N(4) atom affiliated to the free 4,4?-bipyridine molecule. The hydrogen bond parameters are listed in Table 2 for details. These weak interactions link adjacent moieties into a 1D chain along theplane[14], as illustrated in Fig. 2. In addition, close inspection reveals that the C(9)–C(10)–C(11)– C(12)–C(13)–C(14) benzene ring is parallel to the aromatic ring of the next unit, with the centriod- centriod distance between them to be 3.726 ?. The centriod-centriod distance between the second and third aromatic rings is 4.0892 ?, and both the dihedral angles between the neighboring aromatic rings are 0.00o. So, we can see the existence of weakstacking interactions that connect the compound into a dimer, as illustrated in Fig. 3[15].

Fig. 1. Molecular structure of the title compound with atom-numbering scheme. The H atoms are shown as small spheres of arbitrary radii. Symmetry code: A: –,, –+1/2

Fig. 2. (a) Perspective viewof the dimer unit of the title compoundalong theplane, (b) illustration of the 1D zigzag chain along theplane

Fig. 3. Illustration of the 1D chain of the title compound through hydrogen bonds as well as the π-π stacking interactionsbetween two moieties in the dimer unit

Table 2. Hydrogen Bond Lengths (?) and Bond Angles (°) for the Title Complex

Symmetry transformations used to generate the equivalent atoms: #2:, –+1,–1/2; #3,–1,

The hydrogen bonds between the O(8) and N(4) atoms together withstacking interactions further contribute to the 1D supramolecular architecture. These 1D chains are further connected through hydrogen bonds between the oxygen atoms of coordinated waters and the nitro groups of the secondNSBSH, the hydroxyl groups of the secondNSBSH moiety, as well as the oxygen atoms of sulfonyl hydrazide. It gives rise to the final 2D supramolecular architecture, among which the hy- drogen bond exists between the oxygen atoms of coordinated water and the nitro groups O(2)– H(4W)···O(6)#2 (O···O = 3.332 ?,DO–H···O = 159.93° (#2,,–1,)). This is weak due to the long bond length and large bond angle[16]. Apart from the O–H···O hydrogen bond, the N–H×××O hydrogen bondN(1)–H(1D)···O(2) (O···O = 2.842(2) ?,DO–H···O = 171(2)°) and thestacking interac- tions, the interaction between the O atom and thebond is also very outstanding for this 2D supramole- cular sheet.

By consideration that crystal packing results as the sum of many different contributions of direc- tional and nondirectional intermolecular interactions, it is important that different types of interactions are considered jointly in structure analysis, contributing to the stabilization of the crystal structures of the compounds. As shown in Fig. 4, different types of intermolecular interactions are quantified by density functional theory calculations at theB97X- D/6-31G(d) level of theory. The reliability of theB97X-D functional for the calculations of the noncovalent interactions can be found elsewhere[17, 18]. Thebinding energies are corrected for basis set superposition error using the counterpoise method of Boys and Bernardi[19]. It can be clearly seen from Fig. 4 that the binding energies of the O–H···N hydrogen bond and thestacking interaction are 8.83 and 13.61 kcal/mol, respectively. Thestacking interaction is stronger than the O–H···N hydrogen bond. Evidently, both the O–H···N hydro- gen bond and thestacking interaction are much strong, so they play a dominant role in forming the 1D chain and the crystal packing.

Fig. 4.B97X-D/6-31G(d) binding energies (kcal/mol) of different types of intermolecular interactions in the 1D chain formed between the title compound and 4,4?-bipyridine

3.3 Infrared spectra

In the IR spectrum of the title compound,the strong bands ranging from 1482 to 1627 cm-1indicate the existence of benzene ringin the title compound. The broad and strong absorption of 3450 and 3260 cm-1shows the appearance of free water molecule and hydroxyl group, respectively[20]. Besides, the absorption of 2923 cm-1suggests the occurrence of methyl moiety. The strong vibrations appear around 1635 cm-1, corresponding to the stretching vibrations of C=N group[21]. In addition, the absorption of 1393 and 1192 cm-1indicates the existence of nitro and sulfonyl groups in the title compound[22].

3.4 Photoluminescence property

The photoluminescent property of the title com- poundin the methanol suspension samples (1 × 10-3mol/L) was investigated at room temperature. It shows excited spectra in the region from 400 to 500 nm with the maximum wavelength of 455 nm, which is assigned to the characteristic-* transition within the benzene ring[23], as illustrated in Fig. 5. Upon photoexcitation at 455 nm, the title compound exhibits intense emission bands from 500 to 600 nm in blue regions with the maximum at 522 nm because increasing the conjugation of this organic compound compared with the simple benzene results in the decrease of* energy gap[24].

Fig. 5. Emission spectrum of the title compound in methanol suspension sample at room temperature

Fig. 6. TG and DTA curves for the title compound

3.5 Thermal analysis

The thermal behavior of the title compound was examined by TG-DTA in Fig. 6. The first weight loss is observed in the range of 100～150 ℃, corresponding to the release of free water molecules, which is close to the calculated value of 6.61%. Further weight loss is ascribed to the decomposition of organic compound and the residual weight is 24.65% above 200 ℃. This means the compound has high thermal stability after dehydration of the lattice water.

3.6 Biological activity studies

In vitro antibacterial activity studies were carried out using the standardized disc-agar diffusion method[25]to investigate the inhibitory effect of the title complex against Sarcina. The antibiotic linco- mycin hydrochloride was used as standard reference in the case of Gram-positive bacteria. An inhibition zone diameter indicates that the tested compound is active against the tested bacteria. The test was performed on LB agar medium, which contains 100 ml solid, such as 1 g NaCl, 1 g peptone, 0.5 g yeast, 1.5 g agar, and 5 mL liquid LB. In this experiment, Sarcina was shaken in the cradle for 12 hours at 37 ℃. Filter paper disks in uniform size were impreg- nated by equal volume (10 μL) from the specific concentration of dissolved tested compound and carefully placed on the incubated agar surface[26]. After incubation for 12 h at 37 ℃, the title com- pound has good in vitro antibacterial activity against Sarcina. The minimum inhibitory concentration is 3.81 μg/mL.

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31 March 2014;

19 August 2014 (CCDC 961103)

the National Natural Science Foundation of China (Nos. 21273101 and 21271098 ), the Foundation of the Program for Backbone eachers in Universities of Henan Province (No. 2012GGJS158), tackle key problem of science and technology Project of Henan Province (No. 142102310483), and Program for Science & Technology Innovation Talents in Universities of Henan Province (2014HASTIT014)

. Majoring in coordination chemistry. E-mail: wlya@lynu.edu.cn