Synthesis, Characterization and Antimicrobial Activity of Schiff Base (E)-N-(4-(2-Hydroxybenzylideneamino) Phenylsulfonyl) Acetamide Metal Complexes ()
Received 14 December 2015; accepted 1 March 2016; published 4 March 2016
1. Introduction
Schiff bases are the compounds containing azomethine group (-HC=N-) which were first reported by Hugo Schiff in 1864 and formed by condensation of a primary amine with an active carbonyl compound, and generally take place under acid, base catalysis or with heat [1] [2] . They are important compounds owing to their wide range of biological activities and industrial application; they have been found to posses the pharmacological activities such as anti-malarial [3] , anticancer [4] , antibacterial, antifungal [5] , anti-tubercular [6] , and anti-in- flammatory [7] . Sulfonamide derivatives have been subjected to intensive studies, where a wide variety of those derivatives have been prepared and used in various biological and pharmacological fields. Schiff bases are derived from sulfonamide derivatives which have been used for numerous biological applications [8] [9] . The usage of Zn(II), Cu(II), Ni(II), Ce(III), Bi(III), Cd(II), Hg(II), Sm(III) and UO2 sulfonamide Schiff base has been reported showing its versatility in coordination chemistry and medicinal chemistry, for examples, cobalt(II), copper(II), nickel(II) and zinc(II) complexes of mercaptothiadiazole-derived from furanyl, thienyl, pyrrolyl, salicylyl and pyridinyl Schiff bases [10] , anti-tuberculosis agent and pharmacological activities of sulfonamide copper complexes [11] , crystal structure of zinc(II) 2-sulfanilamidopyrimidine [12] , sulfamethoxydiazine complexes of copper(II), zinc(II), nickel(II), cadmium(II), chromium(III) and iron(III) [13] , disulfamethoxazole diaquo Ni(II) monohydrate [14] , Copper complexes with sulfonamides with pUC18 plasmid and hydrogen peroxide [15] , binuclear dioxomolybdenum(VI) chelates involving Schiff bases derived from sulpha drugs and 4- benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one [16] , sulfa oxovanadium(IV) complexes involving the O,N-do- nor environment of pyrazolone-based drug Schiff bases [17] , mixed ligand complexes of Cu(II), Ni(II), Co(II), Zn(II), Sm(III), and UO2(VI) with a Schiff Base derived from the sulfamerazine and 2,2′-bipyridine [18] . Currently, several methods are used for the determination of transition metal ions, such as atomic absorption spectroscopy (AAS), inductively coupled plasma atomic emission spectrometry (ICP-AES), inductively coupled plasma mass spectrometry (ICP-MS), and ion chromatography (IC). However, simultaneous multi-element analysis for AAS is impossible, while ICP-AES and ICP-MS instruments are most suitable. ICP-MS is another analytical method to determine elements. It is capable to detect mainly metals and several nonmetals. It has many advantages compared to other elemental analysis techniques such as atomic absorption and emission spectrometry including ICP-AES. The advantages are: 1) it has equal or better detection limits for most elements than Graphite Furnace Atomic Absorption Spectroscopy (GFAAS); 2) it has higher throughput than GFAAS; 3) it can handle both simple and complex matrices with minimum matrix interferences due to the high temperature of ICP source; 4) it has superior detection capability to ICP-AES under the same sample throughput; 5) it has ability to obtain isotropic information [19] . The present work was devoted to elucidating the structures of new series of Ag, Cd(II), Ce(III), Co(II), Cr(III), Fe(III), Ni(II) and Pb(II) complexes with (E)-N-(4-(2-hydroxyben- zylideneamino) phenylsulfonyl) and to check their biological activities.
2. Experimental
2.1. Materials and Methods
All chemicals and solvents employed in synthesis were of extra-pure grade and used as received without any further purification. Sulfacetamide were obtained as a donated sample from Epico Pharm (Cairo Egypt). Melting points were taken on (BI Bamtead Electothermal) and are uncorrected. TLC was visualized by VL-6-LC, UV lamp. Elemental analysis (C, H, N, S) was carried out at Fisons EA 1108 CHNS Micro analyzer. Metal ions concentrations were measured using ICP-MS Perkin Elmer/Optima 7000 with a Cetax LSX-200 UV laser module. The UV spectra of compounds were recorded by UV-Vis. Spectrophotometer (UV-1700, Shimadzu). Molar conductance measurements were made in DMF at 25˚C ± 5˚C using a Systronics conductivity bridge model 305. Magnetic susceptibility was measured on powdered samples using the Sherward scientific magnetic susceptibility balance. The diamagnetic corrections were made by Pascal’s constant and Hg[Co(SCN)4] was used as the calibrant. Mass spectral analysis were measured using Shimadazu Qp-2010 plus. Infrared spectra were recorded by a Perkin-Elmer FT-IR 1650 spectrophotometer in wave number region 4000 - 400 cm−1 as KBr pellet. The 1H NMR spectra were recorded using Mercury-300 bb “NMR 300 MHz”, using DMSO-as solvent and tetramethylsilane (TMS) as an internal standard. Antibacterial and antifungal activities measured at The Regional Center for Mycology and Bitechnology, Al-Azhar University, Cairo, Egypt.
2.2. Synthesis of Schiff Base
The compounds were prepared by adding a hot ethanolic solution of Salicylaldehyde (0.03 mole) to a hot etanolic solution of (0.03 mole) sulfacetamide with vigorous stirring in 1:1 molar ratio, the reaction refluxed for 3 hours until a yellow precipitate formed, which then washed several times and recrystallized from ethanol, and dried in a vacuum over anhydrous calcium chloride The crude product was further purified by preparative TLC (silica gel) as adsorbent(stationary phase) using Di ethyl ether/EtOAc (1:1) (mobile phase) to afford the desired product.
Melting point was (209˚C - 211˚C) yield 70%, molecular weight (318.07) g per mol C15H14N2O4S, Elemental analysis: calc. (found): C 56.59 (55.97), H 4.43 (4.80), N 8.80 (8.31), S 10.07 (10.01).
2.3. Synthesis of the Schiff Base Metal Complexes
Silver complex was prepared by adding a hot water solution of AgNO3 (0.03 mole) with vigorous stirring to a hot etanolic solution of (E)-N-(4-(2-hydroxybenzylideneamino) phenylsulfonyl) acetamide {S.S} (0.03 mole) in 1M:1L molar ratio, the remaining complexes were prepared by adding a hot etanolic solution (or distilled water) of metal salt (0.03 mole) to a hot etanolic solution of ligand (0.06 mole) in 1M:2L molar ratio M:L. The reaction refluxed for many hours until a colored (or sometimes white) precipitate formed, which then washed several times and recrystallized from ethanol (or distilled water) then dried in a vacuum over anhydrous calcium chloride.
2.4. Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
5 ml of the internal standard is added to a test tube along with 10 - 500 microliters of metal complex sample (internal standard consists primarily of deionized water, with nitric or hydrochloric acid, and Indium and/or Gallium, depending on the sample type). This mixture is then vortexed for several seconds until it is sufficiently mixed and then loaded onto the auto sampler tray. Operation Parameters for determination of elements by ICP- MS are shown in Table 1.
3. Results and Discussion
Most of the complexes were colored, stable at room temperature for extended periods, decompose on heating., they are insoluble in water and many common organic solvents (S.S-Co 2:1 complex was readily soluble in water). They are readily soluble in strong coordinating solvents like DMF and DMSO. The analytical data showed that the most of the complexes had stoichiometry of the type [ML2(H2O)2], where M is metal and L is {S.S} ligand, except Ag complex forming a silver salt of Schiff base reacts in 1L:1M molar ratio (Ag L), as shown in Figure 1 & Figure 2, and Table 2.
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Table 1. Illustrates operation parameters for determination of elements by ICP-MS.
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Figure 1. Shows condensation reaction between Salicylaldehyde and Sulfacetamide followed by reaction with metal salt forming the proposed structures of metal complexes, where M = Cd, Co, Ni or Pb (X = Y = H2O); M = Cr (X = H2O, Y = Cl); M = Ce (X = H2O, Y = NO3); M = Fe(III) (X = Y = H2O) and the complex is charged [C30H30FeN4O10S2]3+(NO3)3−3∙3(H2O).
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Figure 2. Shows proposed structure for Ag complex (a silver salt of Schiff base).
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Table 2. Analytical and physical data. {S.S} (E)-N-(4-(2-hydroxybenzylideneamino) phenylsulfonyl.
According to pervious data the reaction of forming Schiff base and complexes can be expressed as shown in Figure 1.
In case of Ag complex the proposed structure is as shown in Figure 2.
3.1. Elemental Analyses of the Complexes
The results of elemental analyses as shown in Table 3, which are in a good agreement with those required by the proposed formula (calculated). Inductively coupled plasma (ICP-MS) technique plays an important role in confirming the structures of the complexes, by determining metal ion concentration. The metal percentages of newly synthesized Schiff base metal complexes which are shown in Table 3, give a good agreement with the proposed formula (calculated), and confirm binding of the metal ion to ligand sites.
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Table 3. Elemental analysis of the complexes Calcd./found.
3.2. IR Spectral Studies
Preliminary identification regarding the formation of Schiff base compound were obtained from the absence of IR bands characteristic for amino group of aryl amine and the carbonyl group of aldehyde. This is further confirmed by the appearance of a new band characteristic of νC=N [20] [21] . As shown in Figure 3. The IR spectrum of Schiff base {S.S}exhibits five potential donor sites, oxygen of the phenolic group (OH), nitrogen of the azomethine group (C=N), sulfonamide oxygen (SO2), nitrogen of secondary amine (NH) and O acetamido (carbonyl group) (C=O). The SO2, C=O, and NH bands nearly not changed indicating they are not involved in coordination., except Ag complex where its NH band has big change 3283 cm−1 compared to ligand 3379 cm−1 indicating involvement of this group in coordination, the other bands in Ag complex nearly not changed. A broad band at 3483 cm−1 characteristic to the stretching vibrations of phenolic O-H group, in the free ligand, the disappearance of this peak in the spectra of most complexes indicates the de-protonation of phenol proton prior to coordination [22] . The band at 1544 cm−1 in the ligand may be assigned as υ C=N stretching vibration of the azomethine group which already shifted to higher frequencies in most complexes suggesting that this group is involved in the coordination with metal [23] . A sharp peaks around 1647 cm−1 is due to C=O stretching vibrations. The bands around 1315 cm−1 and 1145 cm−1 represent the asymmetric and symmetric stretching frequencies of the sulfonyl group (S=O str) respectively [24] . The hydrated complexes exhibited an IR band at approximately br 3450 cm−1range due to ν(H2O), suggesting the coordination of water molecules in most of the complexes. The coordination of oxygen of the phenolic group (OH) and nitrogen of the azomethine group (C=N) atoms is further supported by appearance of two non ligand bands at 539 - 555 cm−1 and 448 - 467 cm−1 due to υM_N and υM_ O respectively, studies on the stretching vibrations of these bonds are important in elucidating the structure of the complex, [25] . In case of Ag complex contain one band at 548 confirming coordination of NH only. Other bands like υC-H Ar appears around 2950 cm−1 and υC-H Al appears around 2800 cm−1, another bands such as C=C appears around 1500 cm−1 [26] . These bands are illustrated in Table 4.
3.3. Molar Conductivity Measurements
By using the relation Λm = K/C, the molar conductance of the complexes (Λm) can be calculated, where C is the molar concentration of the metal complex solutions, K = specific conductivity of the complex. The chelates were dissolved in DMF, the molar conductivities of 10−4 M of their solutions at 25˚C ± 2˚C were measured. Table 5 shows the low molar conductivity values of all complexes (Λm = 6.2 - 27.43 Ω−1∙mol−1∙cm2) indicates that these complexes are non-electrolytes [27] . Except Fe(III) complex, it has high molar conductance of 195.97 Ω−1∙mol−1∙cm2 indicating electrolytic nature of the complex [28] .
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Figure 3. Shows Infra red spectrum of Schiff base {S.S} ligand.
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Table 5. The UV-Visible spectra, molar conductance and magnetic moment metal complexes.
3.4. Magnetic Susceptibility Measurements
The magnetic moments values, µeff of the Ce(III)complex is 2.98 B.M., being consistent with mononuclear complex and free from antiferromagnetism [29] . Co(II) and Ni(II) complexes have magnetic moment values 4.58 B.M. and 3.22 B.M. respectively which agrees well with the expected value for a high-spin Co(II) ion in an octahedral environment [30] . The Cr complex show a magnetic moment 3.76 B.M. corresponding to 3 unpaired electrons, which is approximately equal to a spin-only value [31] . The observed magnetic moments of Fe(III), is 5.77 B.M. Thus, the complexes formed have octahedral geometry involving d2sp3 hybridization in the Fe ions [32] . On the basis of analytical, conductance and spectral data and the magnetic moments values, µeff, complexes were assigned an octahedral geometry except Ag complex was planner.
3.5. Electronic Spectra
The electronic spectra for all the compounds were obtained in DMSO solutions. The UV-VIS spectra of the ligand {S.S}, showed many bands at 271 nm, and 324 nm, assigned to π → π* (phenyl group nm, C=C), n → π* transitions within the molecule (C=O) respectively [33] . SO2 group merge to form a single strong absorption band around 260. Most bands were slightly shifted to blue or red regions in all complexes indicating coordination of the ligand to the metal. The bands around 450 is characteristic for the ligand to metal charge transfer LMCT) from the nitrogen atom to the transition metal centre. When the NH-proton is lost, the first band is affected while the coordination affects the other bands as well, this observed in Ag complex. The new bands were observed in the visible region for the complexes due to d → d transitions. The Ag and Cd show no d-d bands as is expected for a d10 system and was found to be diamagnetic in nature. Also the Pb, complexes contain only paired electrons and was found to be diamagnetic in nature. The electronic spectrum of the Co(II) complex shows two strong bands at 640 and 496 nm which are assigned to 4T1g → 4 A2g(F) (ν2) and 4T1g(F) → 4T1g(P) (ν3) transitions, respectively, as expected for an octahedral Co(II) complexes. The electronic spectrum of the Ni(II) complex exhibits three bands at 698,633 and 460 nm attributable to 3A2g(F) → 3T2g(F) (ν1), 3A2g(F) → 3T1g(F) (ν2) and 3A2g(F) → 3T1g(P) (ν3) transitions, respectively, for an octahedral Ni(II) complex [34] [35] . Spectrum of Iron (III) complex exhibited three bands in the region 366 - 665 nm that are assignable for 6A1g → 4T1g 6A1g → 4Eg, 4A1g (G) and 6A1g → 4Eg (D) transitions which can be assigned to transition characteristic of octahedral structure [36] . Cerium(III) complex show a new absorption band at 454 nm which may be related to metal-ligand charge transfer excitations The complexes have a coordination number 6 and may exist in octahedral geometries [37] . Chromium(III) complex show three bands 538, 459 and 253 nm similar to those observed for six coordinate chromium complexes [38] .
3.6. Mass Spectra Analysis
The mass spectra of complexes are given in Table 6 as representative examples. The molecular ion peaks are in good agreement with their empirical as indicated from elemental analyses. The other peaks represent fragments of the molecular ions.
3.7. 1H NMR Spectra
1H NMR for ligand {S.S} is shown in Figure 4 and the diamagnetic complexes (Ag, Cd, and Pb complexes) are shown in Table 7. All the protons were found as expected in the spectra of compounds. The spectra of the diamagnetic complexes were examined in comparison with {S.S}, ligand. The diamagnetic complexes and ligand give a duplet signals in the region 6.54 - 7.88 ppm (d) for the aromatic protons. Singlet peaks appeared in the re-
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Table 6. Mass spectral data of the compounds.
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Table 7. Proton NMR spectral data of the diamagnetic complexes and Schiff base.
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Figure 4. Shows 1H NMR spectrum of Schiff base {S.S} ligand.
gion of 1. 61 - 1.70 ppm were attributed to the methyl group. The N-H proton give a singlet signals in the region 11.82 - 11.89 ppm (s) which nearly not changed compared to ligand, this indicate NH group is not involved in the coordination of Cd and Pb complexes, but the Ag complex we found N-H proton disappeared which confirm participating of this group in the coordination, by losing H proton. Signals for the methine protons of the azomethine group, were observed between 8.96 and 8.40 ppm, the coordination of azomethine nitrogen is confirmed by down field shift in Cd and Pb complexes, also OH appear in ligand at 12.88 ppm but disappear in Cd and Pb complexes ensure coordination of phenolic oxygen to metal ion in Cd and Pb complexes, These numbers of protons results give a good agreement with CHNS calculated and found results.
3.8. Biological Activity
This test was performed using the diffusion agar technique [39] . The sensitivity of a microorganism to antibiotics and other antimicrobial agents was determined by the assay plates, which were incubated at 28˚C for 2 days (for fungi) and at 37˚C for 1 day (for bacteria). Most of the tested compounds showed a promising biological activity against different types of Gram-positive, Gram-negative bacteria, and fungi. The data are listed in Table 8 show that E. coli was inhibited by all complexes. The importance of this lies in the fact that these complexes could reasonably be used for the treatment of some common diseases caused by E. coli, e.g., septicemia, gastroenteritis, urinary tract infections, and hospital-acquired infections, also this promising activity might have a possible antitumor effect since Gram-negative bacteria are considered a quantitative microbiological method for testing beneficial and important drugs, in both clinical and experimental tumor chemotherapy [40] . The mechanism of action of this complex seems to be connected with the inhibition of phosphomannose isomerase, a key enzyme in the bio-synthesis of yeast cell walls. The biological activity of new silver(I) complexes is potentially important, and are developed not only with wound care in mind but some cases of antibiotic resistance, for example, the treatment of lungs chronically infected with cystic fibrosis, it also have successfully been used for the last 20 years for the prophylaxis [41] .
Mean zone of inhibition in mm ± Standard beyond well diameter (6 mm) (100 ml was tested) produced on a range of clinically pathogenic microorganisms using (5 mg per ml) concentration of tested samples. Results are depicted in Table 8.
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Table 8. Biological activity of metal complexes.
4. Conclusion
Based on the above discussions, the prepared Cd(II), Ce(III), Co(II), Cr(III), Fe(III), Ni(II) and Pb(II) complexes with (E)-N-(4-(2-hydroxybenzylideneamino) phenylsulfonyl) showing promising antimicrobial activity and the metal ions concentrations were determined using ICp-MS and gave a good agreement with the formula proposed which involved coordination of metal complexes in a regular octahedral arrangement in 2L:1M molar ratio by two N azomethine and two OH phenolic from the Schiff base {S.S} in the form of [ML2(H2O)2] except Ag complex was planner.
NOTES
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*Corresponding author.