Preparation and characterization of new tetradentate Schiff base metal complexes and biological activity evaluation

Journal of Molecular Structure 1051 (2013) 30–40

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Preparation and characterization of new tetradentate Schiff base metal complexes and biological activity evaluation S.A. Sadeek a,⇑, M.S. El-Attar a, S.M. Abd El-Hamid b a b

Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt Drinking Water and Sanitation Company, Mansoura, Egypt

h i g h l i g h t s  Four new complexes ciprofloxacin Schiff base were synthesized.  The complexes were characterized by using spectroscopic methods.  The antibacterial activity of ciprofloxacin Schiff base and their metal complexes were evaluated.

a r t i c l e

i n f o

Article history: Received 29 May 2013 Received in revised form 24 July 2013 Accepted 28 July 2013 Available online 2 August 2013 Keywords: Tetradentate Schiff base Transition metal complexes Infrared Mass spectra

a b s t r a c t A new Schiff base (N,N0 -ethylene (bis 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazine-1-yl)-quinoline-3-carboxylic acid) and its Zn(II), Zr(IV), Ce(IV) and U(VI) complexes were synthesized and characterized by elemental analysis, molar conductance, IR, UV–Vis, 1H NMR spectra, magnetic moment, thermal analysis as well as mass spectra. The IR results demonstrate that the tetradentate binding mode of the ligand involving azomethine nitrogen and carboxylato oxygen atoms. The calculated bond length and the bond stretching force constant, F(U@O), values for UO2 bond are 1.744 Å and 654.49 N m1. The antimicrobial activity of the synthesized ligand and its complexes were screened and the results showed that the metal complexes were found to be more active than free ligand. Ó 2013 Elsevier B.V. All rights reserved.

1. Introduction Metal-chelated Schiff base complexes have continued to play the role of one of the most important stereochemical models in main group and transition-metal coordination chemistry due to their preparative accessibility, diversity and structural variability [1,2]. Schiff base metal complexes attract considerable interest and occupy an important role in the development of the chemistry of chelate systems [3,4] due to the fact that especially these with N2O2 tetradentate ligands, such systems closely resemble metallo-proteins. Some Schiff base complexes are also used as model molecules for biological oxygen carrier systems [5] as well as having applications in analytical fields [6]. Complexation reactions of transition elements with Schiff bases have been studied extensively [7–11]. Survey of the literature reveals a very little work has appeared on complex formation of transition metals with fluoroquinolone drug Schiff base [12]. The present work deals with the preparation and characterization of ciprofloxacin Schiff base (CIP-en) (N,N0 -ethylene (bis ⇑ Corresponding author. Tel.: +20 01220057510; fax: +20 0553208213. E-mail address: [email protected] (S.A. Sadeek). 0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2013.07.053

1-cyclopropyl-6-fluoro-4-oxo-7-(piperazine-1-yl)-quinoline-3-carboxylic acid) followed by studying their complexation with di, tetra and hexavalent transition metal ions. Indeed, the biological activity of the ligand and its complexes were screened against selected kinds of bacteria and fungi. 2. Materials and methods 2.1. Chemicals All chemicals used were of high purity grade and used without further purification. Ciprofloxacin hydrochloride was obtained from the Egyptian International Pharmaceutical Industrial Company (EIPICO). Ethylenediamine, glacial acetic acid, acetone, ethanol, NaOH, FeCl36H2O, BaCl2, AgNO3, FeSO4, K2CrO4 were purchased from Fluka Chemical Co. Zn(NO3)26H2O, ZrOCl28H2O (99.9%), UO2(CH3COO)22H2O and Ce(SO4)2 from Aldrich Chemical Co. 2.2. Synthesis of ligand (CIP-en) (C36H42N8O4F2Cl2) An ethanolic solution of ciprofloxacin (2 mmol, 0.734 g) with ethylene diamine (1 mmol, 0.066 ml) was boiled under reflux in

S.A. Sadeek et al. / Journal of Molecular Structure 1051 (2013) 30–40

the presence of 0.5 ml glacial acetic acid separately for 4 h. The resulting solution was concentrated to 8 ml on a water bath and allowed to cool at 0 °C. White precipitate was filtered off, washed several times by ethanol and dried under vacuum over CaCl2 in a disecator. The proposed formula of the ligand (C36H42N8O4F2Cl2, M.wt. = 759) is in good agreement with mass spectrum (M+) at m/z = 758 (66.98%) and confirmed by IR spectral data. The 1H NMR spectrum of the ligand in DMSO-d6 showed signals at d 11.0 ppm assigned to the proton of carboxylic (COOH). 2.3. Synthesis of metal complexes The light brown solid complex [Zn(CIP-en)(H2O)2](NO3)27H2O was prepared by adding 0.5 mmol (0.148 g) of Zn(NO3)26H2O in 20 ml ethanol drop-wisely to a stirred suspended solution of CIPen (0.5 mmol, 0.379 g) and NaOH (1 mmol, 0.04 g) in 50 ml ethanol. The reaction mixture was stirred for 15 h at 35 °C in a water bath. The light brown precipitate was filtered off and dried under vacuum over anhydrous CaCl2. The light yellow, yellow and dark yellow solid complexes of [ZrO(CIP-en)Cl]Cl9H2O, [Ce(CIP-en) (H2O)2](SO4)26H2O and [UO2(CIP-en)](OCH3CO)26H2O were prepared in a similar manner described above by using acetone as a solvent and using ZrOCl28H2O, Ce(SO4)2 and UO2(CH3COO)22H2O, respectively, in 1:1 molar ratio. All compounds were characterized by their elemental analysis, molar conductance, magnetic moment, IR, 1H NMR, electronic, mass spectra as well as thermal analysis. We did not manage to obtain a crystal of the complexes suitable for the structure determination with X-ray crystallography, although diverse crystallization techniques were used. Elemental C, H, N and halogen analysis was carried out on a Perkin Elmer CHN 2400. The percentage of the metal ions were determined gravimetrically by transforming the solid products into metal oxide or sulfate and also determined by using atomic absorption method. Spectrometer model PYE-UNICAM SP 1900 fitted with the corresponding lamp was used for this purposed. IR spectra were recorded on FTIR 460 PLUS (KBr discs) in the range from 4000 to 400 cm1, 1H NMR spectra were recorded on Varian Mercury VX-300 NMR Spectrometer using DMSO-d6 as solvent. TGA–DTG measurements were carried out under N2 atmosphere within the temperature range from room temperature to 800 °C using TGA-50H Shimadzu, the mass of sample was accurately weighted out in an aluminum crucible. Electronic spectra were obtained using UV-3101PC Shimadzu. The solid reflection spectra were recorded with KBr pellets. Mass spectra were recorded on GCMS-QP-1000EX Shimadzu (ESI-70ev) in the range from 0-1090. Magnetic measurements were carried out on a Sherwood scientific magnetic balance using Gouy method using Hg[Co(SCN)4] as calibrant. Molar conductivities of the solution of the ligand and metal complexes in DMF at 1  103 M were measured on CONSORT K410. All measurements were carried out at ambient temperature with freshly prepared solution.

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NaCl and 1.5% Agar–Agar) and czapeks Dox medium for antifungal (3% Sucrose, 0.3% NaNO3, 0.1% K2HPO4, 0.05% KCl, 0.001% FeSO4, 2% Agar–Agar) was prepared [14] and then cooled to 47 °C and seeded with tested microorganisms. Sterile water agar layer was poured, solidified then pour, the prepared growth medium for fungi and bacteria (plate of 12 cm diameter, 15 ml medium plate). After solidification 5 mm diameter holes were punched by a sterile cork-borer. The investigated compounds, i.e., ligand and their complexes, were introduced in Petri-dishes (only 0.1 ml) after dissolving in DMF at 1.0  103 M. These culture plates were then incubated at 37 °C for 20 h for bacteria and for seven days at 30 °C for fungi. The activity was determined by measuring the diameter of the inhibition zone (in mm). Bacterial growth inhibition was calculated with reference to the positive control, i.e., Ampicilin, Amoxycillin and Cefaloxin. 3. Results and discussion The analytical data of the ligand and its complexes along with some physical properties are summarized in Table 1. The ligand on interaction with Zn(II), Zr(IV), Ce(IV) and U(VI) ions yield complexes corresponding to the general formula [M(CIP-en)(H2O)2]+n (M = Zn(II) and Ce(IV)), [ZrO(CIP-en)Cl]+ and [UO2(CIP-en)]+2. The complexes were characterized through their elemental analysis, IR, UV–Vis, 1H NMR, melting point, molar conductivity, magnetic properties as well as thermogravimetric analyses. The results enable us to characterize the complexes and make an assessment of the bonding and structures inherent in them. All the prepared complexes contain water molecules and the number of bound water molecules in these complexes being different. The IR spectroscopic and thermogravimetric data confirm water in the composition of the complexes. Also, the molar conductance value of free (CIP-en) is 138.2 S cm2 mol1 at room temperature and the corresponding values of the complexes at the same temperature were found to be in the range from 186.8 to 272.8 S cm2 mol1. The higher molar conductance values of the complexes compared with the ligand reveal their electrolytic nature [15] (Table 1). The magnetic moments (as B.M.) of the complexes were measured at room temperature where Hg[Co(SCN)4] were used a calibrant. The Zn(II), Zr(IV), Ce(IV) and U(VI) complexes are found in diamagnetic character with molecular geometries octahedral. Qualitative reactions for the isolated complexes of Zn(II), Zr(IV), Ce(IV) and U(VI) revealed the presence of nitrate, chloride, sulfate and acetate ions as counter ions (outside the complexes sphere) and not coordinate, the complexes solution were tested with an aqueous solutions of ferrous sulfate, silver nitrate, , barium chloride and ferric chloride a black ring (FeSO4NO) for Zn(II), a white precipitate for Zr(IV) and Ce(IV) and a red brown for U(VI) were formed [16]. This indicate that nitrate, chloride, sulfate and acetate ions are found as counter ions which in good agreement with the results of molar conductance and infrared data.

2.4. Antimicrobial investigation 3.1. IR absorption spectra Antibacterial activity of the ligand and its metal complexes was investigated by a previously reported modified method of Beecher and Wong [13] against different bacterial species, such as Staphylococcus aureus (S. aureus), Bacillus subtilus (B. subtilus), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) and antifungal screening was studied against two species, Candida albicans and Aspergillus fumigatas. The tested microorganisms isolates were isolated from Egyptian soil and identified according to the standard mycological and bacteriological keys for identification of fungi and bacteria as stock cultures in the microbiology laboratory, Faculty of Science, Zagazig University. The nutrient agar medium for antibacterial was (0.5% Peptone, 0.1% Beef extract, 0.2% Yeast extract, 0.5%

The mid infrared spectra of CIP-en Schiff base and their metal complexes [Zn(CIP-en)(H2O)2](NO3)27H2O, [ZrO(CIP-en)Cl] Cl9H2O, [Ce(CIP-en)(H2O)2](SO4)26H2O and [UO2(CIP-en)](OCH3 CO)26H2O were recorded from KBr discs. As expected, the absorption bands characteristic of CIP-en Schiff base acting as tetradentate unit in the complexes are observed with small changes in band intensities and wave number. Before discussing the assignments of the infrared spectra, the proposed structures of the complexes must be considered. Here, metal ions react with these tetradentate Schiff base forming complexes of monomeric structure where the metal ions is six coordinated [17,18] (Scheme 2).

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Table 1 Elemental analysis and physico-analytical data for ciprofloxacin Schiff base (CIP-en) and its metal complexes. Compounds M.Wt. (M.F.)

Yield%

Mp/°C

Color

(CIP-en) 759 (C36H42N8O4F2Cl2) [Zn(CIP-en)(H2O)2](NO3)27H2O

85.0

322

White

73.16

302

Light brown

1037.4 (ZnC36H58N10O19F2) [ZrO(CIP-en)Cl]Cl9H2O

73.96

280

1026.2 (ZrC36H58N8O14F2Cl2) [Ce(CIP-en)(H2O)2](SO4)26H2O

65.31

1162.2 (CeC36H56N8O20F2S) [UO2(CIP-en)](OCH3CO)26H2O

64.21

Found (Calcd.) (%)

leff (B.M.)

K (S cm2 mol1)

C

H

N

M

Cl

S

(56.92) 56.90 (41.64) 41.60

(5.53) 5.50 (5.59) 5.59

(14.76) 14.76 (13.50) 13.46

–

–

Diamagnetic

138.2

(6.30) 6.30

(9.35) 9.35 –

–

Diamagnetic

212.8

Light yellow

(42.10) 42.08

(5.65) 5.60

(10.91) 10.88

(8.89) 8.88

(3.46) 3.46

–

Diamagnetic

222.8

290

Yellow

(37.17) 37.16

(4.82) 4.80

(9.64) 9.62

(12.05) 12.03

–

(2.76) 2.76

Diamagnetic

272.8

>360

Dark yellow

(40.61) 40.60

(4.91) 4.89

(9.48) 9.44

(20.14) 20.14

–

–

Diamagnetic

186.8

1182.03(C40H58N8O16F2U)

For uranyl complex the two oxygen of uranyl group occupy axial position perpendicular to a plane occupied by the different coordinating sites of the Schiff base. Thus in this complex we propose that the uranyl group is surrounded by carboxylic oxygens and two nitrogen of azomethine groups of the tetradentate Schiff base in a plane forming an irregular tetragon. The non-existence of coordinated solvent in the case of [UO2(CIP-en)]+2 may be associated with steric hinderance around UO2 unit arising from the existence of one more phenyl group in the ligand used [UO2(CIP-en)]+2. Accordingly, the complex [UO2(CIP-en)]+2 may take the structure shown in (Scheme 2) where the ligand is coordinated to U(VI) in a plane with the uranyl group, UO2, perpendicular to it [19]. Also for Zn(II) and Ce(IV) complexes the metal ions is six coordinated (Scheme 1) where the two oxygen and the two nitrogen atoms of the Schiff base occupy equatorial positions and the axial positions are occupied by the oxygen atoms of the two coordinated water molecules. These structures may belong to C2m symmetry [18,20,21]. The C2m complexes, [M(CIP-en)(H2O)2]+n (M = Zn(II) and Ce(IV)) and [UO2(CIP-en)]+2 are expected to display 285 and 273 vibrational fundamentals, respectively, which all are monodegenerate and distributed between A1, A2, B1 and B2 motions. Under such symmetry, the four vibrations of the uranyl unit ,UO2, in the complex [UO2(CIP-en)]+2 are of the type 2A1, B1 and B2, ms(U@O), A1; mas(U@O), B1; d(UO2), A1 and d(UO2), B2. The data showed that mas(U@O) and ms(U@O) absorption bands occurs as a very strong

Scheme 1. The coordination mode of M with ciprofloxacin Schiff base (CIP-en).

singlet at 899 and 822 cm1, respectively. These assignments agree quite well with those known for many dioxouranium(VI) complexes [22–24]. The m(U@O) of the uranyl unit occurs at lower frequency values compared with those for the same unit, UO2, in simple salts and this is consistent with the formation of the complex. The decrease of m(U@O) upon coordination could be caused by two reasons. First, the expected increase of the U(VI) mass upon coordination is likely to decrease the frequency values of m(U@O).

Scheme 2. The coordination mode of Zr(IV) and U(VI) with ciprofloxacin Schiff base (CIP-en).

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Second, the increase of electron density on U(VI) by the Schiff base is expected to increase the electron repulsion between the uranyl oxygens and lowering the U@O bond strength and hence the bond frequency. The ms(U@O) value was used to calculate both the bond length and the bond stretching force constant, F(U@O), for UO2 bond in our complex [21,23]. The calculated bond length and force constant values are 1.744 Å and 654.49 N m1, respectively. The [ZrO(CIP-en)Cl]+ complex contains only a plane of symmetry and hence the complex may belong to CS symmetry and display 273 vibrational fundamentals and all vibrations are distributed between motions of the types An and Ann 1 all are monodegenerate, infrared and Raman active. The infrared spectra of ciprofloxacin Schiff base metal complexes exhibit a broad band in the region 3411–3222 cm1, confirms the presence of water molecules in all complexes [25,26]. The stretching vibrations m(CAH) of phenyl groups, ACH2 and ACH3 units in these complexes are assigned as a number of bands in the region 3178–2719 cm1 [27]. The NAH vibration of the piperazinyl appears in the region of 2667–2473 cm1, it indicates that the ciprofloxacin Schiff base exist in zwitterionic form [28,29]. The two bands observed at 1728 and 1624 cm1 in the spectrum of the free ciprofloxacin Schiff base

have been assigned to the stretching vibration of carboxylic m(COOH) and the azomethine group m(C@N), respectively, [27,30–35]. The absent of the band at 1728 cm1 in complexes and the shift of the characteristic band of azomethine group to a lower value from 1624 cm1 to 1566 cm1 for Zn(II) at 1578 cm1 for Zr(IV) and Ce(IV) at 1570 cm1 for U(VI) indicate the involvement of C@N group and oxygen of carboxylic group in the interaction with metal ion forming five and six membered rings and the carboxylic group is deprotonated [36,37]. In the case of monodentate carboxylate ligand, the antisymmetric and symmetric COO stretches will be shifted to higher and lower frequencies , respectively, with an average Dm > 200 cm1 [38–40]. For our complexes the presence of bands with different intensities at 1624 cm1 in the IR spectra of the metal ciprofloxacin Schiff base complexes can be assigned to the asymmetric stretching vibration mas(C@O) of the ligated carboxylato group and the symmetric vibration occurs in the region 1385–1381 cm1 with different intensities [41,42], with Dm > 200 cm1 indicated that the carboxylate group react as monodentate through one of oxygen atom.

Table 2 UV–Vis spectra of (CIP-en); Zn(II), Zr(IV), Ce(IV) and U(VI). Assignments (nm)

(CIP-en)

p–p* transitions n–p* transitions

209, 241 278, 320 –

Ligand–metal charge transfer

(CIP) Schiff base complex with Zn(II)

Zr(IV)

Ce(IV)

U(VI)

219 281, 362 502, 610, 648

227, 254 298 500, 549, 610

210, 233 310 495, 502, 552, 610

223 275, 398 450, 510, 565, 613

Fig. 1. 1H NMR spectra for (A) (CIP-en), (B) [Zn(CIP-en)(H2O)2](NO3)27H2O, (C) [ZrO(CIP-en)Cl]Cl9H2O, (D) [Ce(CIP-en)(H2O)2](SO4)26H2O and (E) [UO2 (CIP-en)](CH3COO)26H2O.

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Table 3 H NMR values (ppm) and tentative assignments for (A) (CIP-en); (B) [Zn(CIP-en)(H2O)2](NO3)27H2O, (C) [ZrO(CIP-en)Cl]Cl9H2O, (D) [Ce(CIP-en)(H2O)2](SO4)26H2O and (E) [UO2(CIP-en)](CH3COO)26H2O. 1

A

B

C

D

E

Assignments

1.03–1.32 2.49–2.77 2.94–3.86 – 7.53–8.66 11

1.10–1.33 2.49–2.73 3.15–3.84 4.90 7.56–8.68 –

1.05–1.32 2.49–2.80 2.95–3.84 4.55 7.53–8.66 –

1.06–1.33 2.49–2.79 3.02–3.84 4.72 7.55–8.67 –

1.08–1.40 2.35–2.76 2.92 4.92 7.52–9.07 –

dH, ACH2 and ACH cyclopropane dH, A+NH2 and ACH2 aliphatic (ethylene) dH, ACH2 aliphatic (piperazine ring), d H, H2O dH, ACH2 aromatic dH, ACOOH

Fig. 2. TGA and DTG diagrams for (A) (CIP-en), (B) [Zn(CIP-en)(H2O)2](NO3)27H2O, (C) [ZrO(CIP-en)Cl]Cl9H2O, (D) [Ce(CIP-en)(H2O)2](SO4)26H2O and (E) [UO2(CIPen)](CH3COO)26H2O.

The spectra of the isolated solid complexes showed a group of bands with different intensities which characteristics for m(MAO), (MAN). The m(MAO) and (MAN) bands observed at 544 and 502 cm1 for Zn(II), at 667 and 471 cm1 for Zr(IV), at 544 and 440 cm1 for Ce(IV) and finally at 667 and 498 cm1 for U(VI), which are absent in the spectrum of ciprofloxacin Schiff base. The metal-oxygen (of the ligand) stretching vibrations are assigned at higher value than the metal-nitrogen (of the ligand), these assignments agree with those reported previously for related complexes [19]. The assignment of the m(MAN) at a much lower frequency value compared with those of m(MAO) (oxygen of the Schiff base) is in agreement with the crystal structure of related Schiff base complexes indicating that UAN bond is long compared with the UAO bond [19,21]. This indicates the coordination of (CIPen) through both C@N and carboxylic groups.

3.2. Electronic spectra The formation of the metal complexes was also confirmed by UV–Vis spectra. The electronic solid reflection spectra of the free ciprofloxacin Schiff base (CIP-en) and its metal complexes in the wavelength interval from 200 to 800 nm were recorded. It can be seen that free ciprofloxacin Schiff base reflected at 209, 241, 278 and 320 nm (Table 2). The first two bands at 209 and 241 nm may be attributed to p–p* transition and the second two bands observed at 278 and 320 nm are assigned to n–p* transitions, these transitions occur in case of unsaturated hydrocarbons which contain ketone or azomethine groups [43]. The shift of the reflection bands to higher values (bathochromic shift) and the absent of the band at 320 nm in case of Zn(II), Zr(IV), Ce(IV) and U(VI) complexes and presence of new bands in the reflection spectra of complexes

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S.A. Sadeek et al. / Journal of Molecular Structure 1051 (2013) 30–40 Table 4 The maximum temperature Tmax (°C) and weight loss values of the decomposition stages for Zn(II), Zr(IV), Ce(IV) and U(VI). Compounds

Decomposition

Tmax (°C)

(CIP-en) C36H42N8O4F2CL2))

First step Total loss Residue First step Second step Total loss Residue First step Second step Third step Total loss Residue First step Second step Total loss Residue First step Second step Total loss Residue

132, 211, 320, 654

[Zn(CIP-en)(H2O)2](NO3)27H2O (C36H58N10O19F2Zn)

[ZrO(CIP-en)Cl]Cl9H2O (C36H58N8O14F2Cl2Zr)

[Ce(CIP-en) (H2O)2](SO4)26H2O (C36H56N8O20F2SCe)

[UO2(CIP-en)](OCH3CO)26H2O (C40H58N8O16F2U)

Weight loss (%)

60 138, 300, 429, 550

127 173 332,409, 509, 661, 814

66,125 170, 310, 398, 763, 932

55,130 195, 355, 568

indicated the formation of their metal complexes. The four complexes have new bands in the range from 450 to 648 nm which may be assigned to the ligand to metal charge-transfer [33,34,44]. Finally, the results presented here, clearly indicate that the metal ions form stable solid complexes with the Schiff base, CIP-en and monodentate ligand such as H2O where metal ions are six coordinate. 3.3. 1H NMR spectra Evidently, 1H NMR spectra of CIP-en Schiff base and its metal complexes (Fig. 1) confirms the suggested structures and the results obtained from the elemental analyses and IR spectra are proved by considering the changes of the 1H NMR spectra of complexes in comparison with that of the free Schiff base ligand. The comparison reveals that the peak assigned to the proton of ACOOH group (11 ppm in the spectrum of free ligand) disappears indicated coordination of CIP-en to Zn(II), Zr(IV), Ce(IV) and U(VI) through the deprotonated carboxylic group [12,17,34,35] while new peaks are observed in the range 4.55–4.92 ppm due to presence of H2O molecules in all complexes. On the other hand, the values, d (ppm) of protons of ACH3, ACH2 and aromatic ring are decreased and the intensity of peaks is decreased also, as shown in Table 3 [45]. 3.4. Thermal studies To confirm the proposed formulae for all compounds, thermogravimetric (TG) and differential thermogravimetric analysis (DTG) were carried out under N2 flow. TG curves are shown in Fig. 2. Table 4 reflects the maximum temperature values, Tmax/°C, together with the corresponding weight losses for each step of decomposition reactions of the compounds. The obtained data strongly support the formulae proposed for all compounds and indicated that the thermal decomposition of CIP-en Schiff base in inert atmosphere proceed approximately in one stage at four maxima 132, 211, 320 and 654 °C and is accompanied by a weight loss of 100% corresponding to lose of 16C2H2 + 4CO + 2HF + 3N2 + 2NH4Cl. The ciprofloxacin Schiff base (CIP-en) of Zn(II), Zr(IV), Ce(IV) and U(VI) complexes are stable at room temperature and can be stored for several months without any changes. The TGA curve of [Zn(CIP-en)(H2O)2](NO3)27H2O exhibits approximately two stages of decomposition. The first stage occurs

Calc.

Found

100 100 – 12.15 80.01 92.16 7.84 8.77 7.01 72.60 88.38 11.62 9.29 58.00 67.29 32.71 9.14 68.36 77.50 22.50

100 100 – 12.20 80.00 92.20 7.80 8.77 7.01 73.31 89.09 10.91 9.47 57.91 67.38 32.62 9.60 68.46 78.06 21.94

Lost species

16C2H2 + 4CO + 2HF + 3N2 + 2NH4Cl

7H2O 18C2H2 + 8NO + 2HF + N2 + 3H2O

5H2O 4H2O 18C2H2 + NO + 2HF + 2HCl + 2H2O + 3.5N2

6H2O 16C2H2 + 2HF + 3.5N2 + NO + 5H2O

6H2O 18C2H2 + 4CO + 2HF + 4NO + 4NH3

at maximum temperature 60 °C corresponds to the loss of seven water molecules with mass loss of 12.20% (calc.12.15%) [46–48]. The relatively low value of temperature of this step may indicated that these water molecules undergoes less H-bonding. The second step of decomposition occurs at four maxima at 138, 300, 429 and 550 °C, is accompanied by a weight loss of 80.0%. This step is associated with the loss of residue coordinated water molecules and ciprofloxacin Schiff base forming zinc oxide, ZnO, as a final solid product. The actual weight loss from this stage (80.00%) is very close to calculated (80.01%). The thermal decomposition of [ZrO(CIP-en)Cl]Cl9H2O complex proceeds with three main degradation steps. The first stage of decomposition occurs at temperature maximum of 127 °C. The found weight loss associated with step is 8.77% and may be attributed to the loss of the five water molecules which is in good agreement with the calculated values of 8.77%. Also, the second stage of decomposition occurs at temperature maximum of 173 °C. The found weight loss associated with step is 7.01% and may be attributed to the loss of the four water molecules which is in good agreement with the calculated value of 7.01%. The third stage of decomposition occurs at five maxima 332, 409, 509, 661 and 814 °C and the weight loss found at this stage equals to 73.31% corresponds to loss 18C2H2 + NO + 2HF + 2HCl + 2H2O + 3.5N2. The [Ce(CIP-en)(H2O)2](SO4)26H2O complex decomposes in two steps within the temperature range 62-995 °C with total mass loss 67.38% leaving Ce(SO4)2 + 4C as residue (Table 4). For U(VI) complex the thermal decomposition exhibits two main degradation steps. The first step of decomposition occurs from 25 to 140 °C is accompanied by a weight loss of 9.60% in agreement with the theoretical value 9.14% for the loss of six uncoordinated water molecules. The second step of decomposition occurs at three maxima 195, 355 and 568 °C with a weight loss of 68.46% this associated with the loss of ciprofloxacin Schiff base forming uranium oxide as a final product. The proposed structural formula on the basis of the results discussed in our paper located as follows (Schemes 1 and 2).

3.5. Mass spectra Mass spectrometry was found useful as a complementary tool. The structure and stability of coordination complexes under ionization conditions are dependent on various factors like the ligand itself, metal ion, counter ions, solvent, temperature, and

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concentration. Mass spectrum of the free Schiff base (CIP-en) is in a good agreement with the suggested structure (Fig. 3 and Scheme 3). The Schiff base showed molecular ion peak (M+) with m/z = 758 (66.98%) and M+2 at m/z = 760 (2.83%). The molecular ion peak [a] losses C11H25N4Cl2 to give fragment [b] at m/z = 475 (86.79%), also it loses C15H30N4O2Cl2 to give fragment [c] at m/z = 390 (53.77%). The molecular ion peak [a] losses C8H10O4Cl2 to give fragment [d] at m/z = 518 (53.77%) and it also loses C12H20N2O4Cl to give fragment [e] at m/z = 467 (66.98%). It loses C4H6O2Cl to give [f] at m/ z = 637 (76.42%) and loses C3H5Cl to give fragment [g] at m/ z = 682 (62.26%). The fragmentation patterns of our studied

complexes were obtained from the mass spectra (Fig. 3). The mass spectra of Zn(II) and Zr(IV) complexes displayed molecular peak at m/z (%) 1037.4 (36.36%) and 1025.2 (5.13%), respectively, suggesting that the molecular weights of the assigned products matching with elemental and thermogravimetric analyses. Fragmentation pattern of the complex [Zn(CIP-en)(H2O)2] (NO3)27H2O is given as an example in Scheme 4. The molecular ion peak [a] appeared at m/z = 1037.4 (36.36%) losses five molecules of water to give [b] at m/z = 947.4 (27.97%) and it losses two molecules of water and (NO3)2 to give [c] at m/z = 877.4 (45.45%). The molecular ion peak [a] losses C3H15O5 to give [d] at

Fig. 3. Mass spectra diagrams for (A) (CIP-en), (B) [Zn(CIP-en)(H2O)2](NO3)27H2O, (C) [ZrO(CIP-en)Cl]Cl9H2O, (D) [Ce(CIP-en)(H2O)2](SO4)26H2O and (E) [UO2 (CIP-en)](CH3COO)26H2O.

S.A. Sadeek et al. / Journal of Molecular Structure 1051 (2013) 30–40

37

Scheme 3. Fragmentation pattern of free Schiff base (CIP-en).

m/z = 906.4 (56.64%) and it loses C8H20N6O6 to give [e] at m/ z = 741.4 (15.38%). The molecular ion peak [a] loses C3H5N2O6 to give fragment [f] at m/z = 872.4 (48.95%) and it loses C14H30N6O6 to give fragment [g] at m/z = 659.4 (57.34%). For the other two complexes U(VI) and Ce(IV) with the calculated molecular weights, 1182.03 and 1162.2, respectively, according to the elemental analysis and thermogravimetric analysis, the molecular peaks are found outside the scale of the instrument.

3.6. Biological activity The in vitro biological screening effects of the investigated compounds were tested against four bacterial strains; Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) as Gramnegative, Staphylococcus aureus (S. aureus) and Bacilius subtilis (B. subtilis) as Gram-positive also antifungal screening was studied against two species, Candida albicans and Aspergillus fumigatas

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Scheme 4. Fragmentation pattern of [Zn(CIP-en)(H2O)2](NO3)27H2O.

microorganisms. The results of the antibacterial study of Schiff base (CIP-en) and four complexes (Fig. 4 and Table 5) have inhibitory action against all four types of bacteria and no antifungal activity for (CIP-en) and their metal complexes. The complex U(VI) shows a moderate activity against Gram-negative and Gram-positive microorganisms than Schiff base. For Ce(IV) complex shows very highly significant against Pseudomonas aeruginosa but Ce(IV) shows very highly significant against Bacilius subtilis. The nature of the metal ion coordinated to a drug may have a significant role to this diversity. Also, the chelation considerably reduces the polarity of the metal ion because of the partial sharing of its positive charge with the donor groups and possible p-electron delocalization over the chelate ring. Such

chelation increase the lipophilic character of the central metal ion, which subsequently favors the permeation through the lipid layer of cell membrane [49,50]. It is likely that the increased liposolubility of the ligand up on metal chelation may contribute to its facile transport into the bacterial cell which blocks the metal binding sites in enzyme of microorganisms. In general for metal complexes showing antimicrobial activity, the following five principal factors [51–53] should be considered: (i) the chelate effect; (ii) the nature of the ligands; (iii) the total charge of the complex; (iv) the nature of the ion neutralizing the ionic complex; and (v) the nuclearity of the metal center in the complex. All of the five above mentioned factors are present in our complexes.

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Fig. 4. Statistical representation for biological activity of (CIP-en) and its metal complexes.

Table 5 The inhibition diameter zone values (mm) for (CIP-en) and its metal complexes. Tested compounds

Microbial species Bacteria

CIP CIP-en [Zn(CIP-en)(H2O)2](NO3)27H2O/CIP-en [ZrO(CIP-en)Cl]Cl9H2O/CIP-en [Ce(CIP-en) (H2O)2](SO4)26H2O/CIP-en [UO2(CIP-en)](OCH3CO)26H2O/CIP-en Zn(NO3)26H2O Zrocl28H2O Ce(SO4)2 UO2(CH3COO)22H2O Ethylenediamine Control (DMF) Standard Ampicilin Amoxycilin Cefaloxin

Fungi

E. coli

P. aeruginosa

B. subtilis

S. aureus

C. albicans

A. fumigatas

27 ± 0.35 35 ± 1.7 37NS ± 1.15 40+1 ± 0.57 43+1 ± 0.73 40+1 ± 1.19 0 0 0 0 0 0 0 0 24 ± 0.34

23 ± 0.11 30 ± 0.25 39+1 ± 1.15 43+2 ± 0.10 50+3 ± 1.15 38+1 ± 0.05 0 0 0 0 0 0 0 0 0

32 ± 0.22 36 ± 1.15 45+1 ± 1.30 51+2 ± 0.46 58+3 ± 0.15 49+1 ± 0.52 0 0 0 0 0 0 28 ± 0.40 22 ± 0.11 27 ± 1.15

26 ± 0.40 38 ± 0.1237 46+1 ± 1.51 44+1 ± 1.15 41NS ± 0.72 45+1 ± 0.45 0 0 0 0 0 0 0 18 ± 1.73 16 ± 0.52

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

ND: non-detectable. i.e., the inhibition zones exceeds the plate diameter. Statistical significance PNS – P not significant, P >0.05; P+1 – P significant, P <0.05; P+2 – P highly significant, P <0.01; P+3 – P very highly significant, P >0.001; Student’s t-test (Paired).

4. Conclusion

Acknowledgements

The new reaction of some transition metals Zn(II), Zr(IV), Ce(IV) and U(VI) with CIP-en Schiff base has been studied. The results of the elemental analysis, mass spectra and thermogravimetric analysis deduced the formation of 1:1 Schiff base/metal ions complexes in all cases. The structure of the formed complexes were further supported by infrared, UV–Vis and 1H NMR. Antimicrobial studies were carried out against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Bacilius subtilis (B. subtilis) and antifungal. The results showed significant increase in antibacterial activity of metal complexes as compared with uncomplexed ligand and no antifungal activity observed for ligand and their complexes.

The author would like to thank the colleagues at University of Zagazig, Faculty of Science, Microbiology Department for performing the antimicrobial measurements (Prof. Dr. Ashraf sabry). References [1] S.A. Sadeek, M.S. Refat, S.M. Teleb, Bull. Chem. Soc. Ethiopia 18 (2) (2004) 149. [2] M. Sarv, O. Atakol, N. Yilmaz, D. Ulku, Anal. Sci. 15 (1999) 401. [3] P.L. Gurian, L.K. Cheatham, J.W. Ziller, A.R. Barron, J. Chem. Soc. Dalton Trans. (1991) 1449. [4] E. Labisbal, J.A. Garcia-Vazquez, J. Romero, S. Picos, A. Sousa, Polyhedron 14 (1995) 663. [5] A. Halve, S. Samadhiya, Orient. J. Chem. 17 (2001) 87. [6] O.A. Weber, T.W. Robinson, V.I. Simeon, J. Inorg. Nucl. Chem. 33 (1971) 2097.

40 [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32]

S.A. Sadeek et al. / Journal of Molecular Structure 1051 (2013) 30–40 B.D. Clercq, F. Verpoort, Adv. Synth. Catal. 34 (2002) 639. B.D. Clercq, F. Lefebvre, F. Verpoort, Appl. Catal. A 247 (2003) 345. S.M.E. Khalil, Chem. Papers 54 (2000) 12. A.H. Osman, Transit. Met. Chem. 31 (2006) 35. C. Sousa, C. Freire, B. de Castro, Molecules 8 (2003) 894. I. Muhammad, I. Javed, I. Shahid, I. Nazia, Turk. J. Biol. 31 (2007) 67. D.J. Beecher, A.C. Wong, Appl. Environ. Microbial. 60 (1994) 1646. E. Fallik, J. Klein, S. Grinberg, C.E. Lomaniee, S. Lurie, A. Lalazar, J. Econ. Entomol. 77 (1993) 985. W.J. Geary, Coord. Chem. Rev. 7 (1971) 81. J.R. Ferraro, A. Waker, J. Chem. Phys. 42 (1965) 1273. S.A. Al-Shihri, Spectrochim. Acta 60 (2004) 1189. S. Patai, Chemistry of the Carbon–Nitrogen Double Bond, Willey, New York, 1970. pp. 238–247. E.M. Nour, I.S. Alnami, N.A. Alem, J. Phys. Chem. Solids 53 (1992) 197. S.A. Sadeek, S.M. Teleb, M.S. Refat, M.A.F. Elmosallamy, J. Coord. Chem. 58 (2005) 1077. E.M. Nour, A.M. AL-Kority, S.A. Sadeek, S.M. Teleb, Synth. React. Inorg. Met-Org. Chem. 23 (1993) 39. S.A. Sadeek, W.H. EL-Shwiniy, J. Mol. Struct. 981 (2010) 130. S.P. Mcglynnm, J.K. Smith, W.C. Neely, J. Chem. Phys. 35 (1961) 105. L.H. Jones, Spectrochim. Acta 15 (1959) 409. J.R. Anacona, C. Toledo, Transit. Met. Chem. 26 (2001) 228. N.J. Garrido, L. Perello, R. Ortiz, G. Alzuet, M.G. Alvarez, E. Canton, M.L. Gonzalez, S.G. Granda, M.P. Priede, J. Inorg. Biochem. 99 (2005) 677. R.M. Silverstein, G.C. Bassler, T.C. Morril, Spectroscopic Identification of Organic Compounds, fifth ed., Wiley, New York, 1991. N. Sultana, M.S. Arayne, S. Gul, S. Shamim, J. Mol. Struct. 975 (2010) 285. N. Sultana, A. Naz, M.S. Arayne, M.A. Mesaik, J. Mol. Struct. 969 (2010) 17. I. Turel, K. Gruber, I. Leban, N. Bukovec, J. Inorg. Biochem. 61 (1996) 197. I. Turel, I. Leban, G. Klintschar, N. Bukovec, S. Zalar, J. Inorg. Biochem. 66 (1997) 77. K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination Compounds, fourth ed., Wiley, New York, 1986. pp. 230–233.

[33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44]

[45] [46] [47] [48] [49] [50] [51] [52] [53]

S.A. Sadeek, J. Mol. Struct. 753 (2005) 1. S.A. Sadeek, W.H. EL-Shwiniy, J. Mol. Struct. 977 (2010) 243. S.A. Sadeek, W.H. EL-Shwiniy, J. Coord. Chem. 63 (2010) 3471. W.M.I. Hassan, E.M. Zayed, A.K. Elkholy, H. Moustafa, G.G. Mohamed, Spectrochim. Acta A 103 (2013) 378. Z.H. Abd El-Wahab, M.R. El-Sarrag, Spectrochim. Acta A 60 (2004) 271. J.A. Davies, C.T. Eagle, A.A. Pinkerton, R. Syed, Acta Cryst. 43 (1987) 1547. G.B. Robertson, P.A. Tucker, Acta Cryst. 39 (1983) 858. H.E. Bryndza, J.C. Calabrese, M. Marsi, D.C. Roe, W. Tam, J.E. Bercaw, J. Am. Chem. Soc. 108 (1986) 4805. K. Nakamoto, Infrared Spectra of Inorganic and Coordination Compounds, Wiley, New York, 1963. pp. 232–236. G.B. Deacon, R.J. Phillips, Coord. Chem. Rev. 33 (1980) 227. M.S. Refat, Spectrochim. Acta A 68 (2007) 1393. K. Nakamoto, P.J. Mccarthy, S. Fujiwara, Y. Shimura, J. Fujita, C.R. Hare, Y. Saito, Spectroscopy and Structure of Metal Chelate Compounds, John Wiley & Sons, New York, London, Sydney, 1968 (chapt. 2). T. Skauge, I. Turel, E. Sletten, Inorg. Chem. Acta 339 (2002) 239. S.A. Sadeek, W.H. EL-Shwiniy, W.A. Zordok, A.M. EL-Didamony, Spectrochim. Acta A 78 (2011) 854. W. Brzyska, M. Hakim, Polish J. Chem. 66 (1992) 413. S.A. Sadeek, M.S. Refat, S.M. Teleb, S.M. El-Megharbel, J. Mol. Struct. 737 (2005) 139. A.M. Beltagi, J. Pharm. Biomed. Anal. 31 (2003) 1079. M. Dolaz, V. McKee, A. Gölcü, M. Tümer, Curr. Org. Chem. 14 (2010) 28. G. Pasomas, C. Dendrinou-Samara, P. Philippakopoulos, V. Tangoulis, C.P. Raptopoulou, E. Samaras, D.P. Kessissoglou, Inorg. Chim. Acta 272 (1998) 24. H.W. Rossmore, S.S. Block (Eds.), Disinfection, Sterilization and Preservation, fourth ed., Lea and Febinger, Philadelphia, 1991. pp. 290–321. A.D. Russell, S.S. Block (Eds.), Disinfection, Sterilization and Preservation, fourth ed., Lea and Febinger, Philadelphia, 1991. pp. 27–59.