КООРДИНАЦИОННАЯ ХИМИЯ, 2010, том 36, № 3, с. 221-226
УДК 541.49
SYNTHESIS AND SPECTRAL STUDY OF BIOLOGICALLY ACTIVE MACROCYCLIC COMPLEXES OF DIVALENT TRANSITION METAL IONS
© 2010 D. P. Singh*, V. Malik, R. Kumar, and K. Kumar
Department of Chemistry, National Institute of Technology, Kurukshetra 136119, India *E-mail: dpsinghchem@yahoo.co.in Received July 13, 2009
The condensation reaction of succinyldihydrazide with glyoxal in the presence of divalent metal ions (1 : 1 : 1) results in the formation of the complexes of type [M(C6H8N4O2)X2], where M = Co(II), Ni(II), Cu(II), Zn(lI),
Cd(II) and X = Cl-, NO3, CH3COO-. The complexes have been characterized with the aid of elemental analyses, conductance measurements and electronic, NMR, infrared spectral studies. On the basis of these studies, a six-coordinated distorted octahedral geometry in which two nitrogen and two carbonyl oxygen atoms are suitably placed for coordination toward metal ion, has been proposed for all the complexes. The complexes were tested for their in vitro antibacterial activity. Some of the complexes showed remarkable antibacterial activities against some selected bacterial strains.
INTRODUCTION
Interest in macrocyclic complexes lies in the preparation of model compounds, which might mimic the biological species, involved in electron-transfer and dioxygen activation processes [1—4]. More recently, the high stability of macrocyclic complexes has been utilized in construction of models for metalloproteinase and in a wide range of technological applications. The study of macro-cyclic ligand and their complexes allows us to probe many of more suitable aspects of reactivity of coordination compounds, which would not be possible in less stable complexes with open noncyclic ligands. Macrocyclic nickel complexes find use in DNA recognition and oxidation [5], while macrocyclic copper complexes find use in DNA binding and cleavage [6]. Template reactions have been widely used for the syntheses of macrocyclic complexes, where the transition metal ion is used as a templat-ing agent [7]. Macrocyclic metal complexes have been useful because of their close relationship with natural products such as vitamin B12 and chlorophyll [8]. Some macrocyclic complexes have been reported to show antibacterial, antifungal, and anti-inflammatory activities [9—11]. Macrocyclic metal chelating agents (DOTA) are useful to detect tumor lesions [12]. Macrocyclic metal complexes of lanthanides, e.g., Gd+3 are used as MRI (Magnetic Resonance Images) contrast agents [13]. Several amide macrocyclic complexes having redox properties have been reported [14, 15]. Prompted by these, a new series of macrocyclic complexes of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) obtained by the template condensation reaction of succinyldihydrazide and glyoxal has been reported. The complexes have been characterized with the help ofvarious physicochemical techniques like molar conductance, elemental analyses, magnetic susceptibilities and IR, NMR, and electronic spectra. These macro-
cyclic complexes were also screened for their in vitro antibacterial activity.
EXPERIMENTAL
Synthesis of complexes. Our several attempts to isolate the free macrocyclic ligand were unsuccessful. Hence, all the complexes were prepared by the template method. To a stirring methanolic solution (~50 cm3) of succinyldihydrazide (10 mmol) was added divalent cobalt, nickel, copper, zinc, and cadmium salts (10 mmol) dissolved in a minimum quantity of methanol (20 cm3). The resulting solution was refluxed for 0.5 h. After that, glyoxal (10 mmol) dissolved in ~20 cm3 methanol was added in the refluxing mixture, and the mixture was again refluxed for 6—8 h. On overnight cooling light colored complex were formed, filtered off, washed with methanol, acetone, and ether, and dried in vacuo (yield 85%). The complexes were soluble in DMF and DMSO. They were found thermally stable up to ~250—290°C and after that decomposition occurred.
The template syntheses of the complexes may be represented by the following scheme:
C4H1oN4O2 + C2H2O2 + MX2 ^-af-
-4 M ( C6H8N4O2) X2 ] + 2H2O
M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II); X = Cl-, NO-, CH3COO-.
Analytical and physical measurements. The microanalyses of C, H, and N were carried out at SAIF, CDRI, Lucknow. The metal contents were determined by standard EDTA methods. Electronic spectra (DMF) were recorded on a Cary 14 spectrophotometer. The magnetic susceptibility measurements were carried out at SAIF, IIT Roorkee. The IR spectra were recorded on a Infrared
Table 1. Analytical data of divalent cobalt, nickel, copper, zinc, and cadmium complexes derived from succinyldihydrazide and glyoxal
Complex Contents (found/calcd), % Color Molecular weight
M C H N
[Co(C6H8N4O2)Cy (I) 19.45/19.79 24.22/24.16 2.13/2.68 18.66/18.79 Dark brown 298
[Co((C6HsN4O2)(NO3)2] (II) 16.29/16.80 20.23/20.51 2.19/2.27 23.29/23.93 Purple 351
[Co(C6HsN4O2)(OAc)2] (III) 17.19/17.10 34.31/34.78 4.01/4.05 16.12/16.23 Dark brown 345
[Ni(C6H8N4O2)Cy (IV) 19.31/19.55 24.17/24.23 2.35/2.69 18.27/18.84 Sky blue 297
[Ni(C6H8N4O2)(NO3)2] (V) 16.28/16.56 20.28/20.57 2.18/2.28 23.30/23.99 Light brown 350
[Ni(C6HsN4O2)(OAc)2] (VI) 16.31/16.86 34.23/34.88 4.00/4.06 16.15/16.27 Dark brown 344
[Cu(C6H8N4O2)Cy (VII) 20.79/20.99 23.31/23.80 2.43/2.64 18.26/18.51 Yellowish brown 302
[Cu(C6H8N4O2)(NO3)2] (VIII) 17.31/17.86 20.10/20.25 2.17/2.25 23.29/23.62 Mustered 355
[Cu(C6HsN4O2)(OAc)2] (IX) 18.54/18.16 34.31/34.33 3.94/4.00 16.00/16.02 Brown 349
[Zn(C6HsN4O2)(OAc)2] (X) 18.68/18.51 34.12/34.18 3.41/3.98 15.34/15.95 Yellowish white 351
[Cd(C6HsN4O2)(OAc)2] (XI) 28.45/28.21 30.09/30.12 3.23/3.51 13.98/14.05 Creamy 398
spectrophotometer in the range 4000—200 cm-1 using Nujol mull at SAIF, Punjab University, Chandigarh. The NMR spectra were recorded on a Bruker NMR spectrometer (300 MHz). The conductivity was measured on a digital conductivity meter (HPG System, G-3001).
Biological measurements. Some of the synthesized macrocyclic complexes were tested for in vitro antibacterial activity against some bacterial strains using spot-on-lawn on Muller Hinton Agar (MHA) [16].
Four test pathogenic bacterial strains, viz., Bacillus cereus (MTCC 1272), where MTCC - Microbial type culture collections, Salmonella typhi (MTCC 733), Escherichia coli (MTCC 739), and Staphylococcus aureus (MTCC 1144), were considered for determination of minimum inhibitory concentration (MIC) of selected complexes.
The test pathogens were subcultured aerobically using Brain Heart Infusion Agar (HiMedia, Mumbai, India) at 37°C (24 h). Working cultures were stored at 4°C in Brain Heart Infusion (BHI) broth (HiMedia, Mumbai, India), while stock cultures were maintained at -70°C in BHI broth containing 15% (v/v) glycerol (Qualigens, Mumbai, India). The organism was grown overnight in 10 ml of BHI broth, centrifuged at 5.000 g for 10 min, and the pellet was suspended in 10 ml of phosphate buffer saline (PBS, pH 7.2). Optical density at 545 nm (OD-545) was
adjusted to obtain 108 cfu/ml followed by plating serial dilution onto plate count agar (HiMedia, Mumbai, India).
Determination of MIC. MIC is the lowest concentration of the antimicrobial agent that prevents the development ofviable growth after overnight incubation. Antimicrobial activity of the compounds was evaluated using spot-on-lawn on MHA (HiMedia, Mumbai, India). Soft agar was prepared by adding 0.75% agar in Muller Hinton Broth (HiMedia, Mumbai, India). Soft agar was inoculated with 1% of 108 Cfu/ml of the test pathogen, and 10 ml were overlaid on MHA. From 1000X solution of compound (1mg/ml ofDMSO) 1, 2, 4, 8, 16, 32, 64, and 128X solutions were prepared. Dilutions of standard antibiotics (Linezolid and Cefaclor) were also prepared in the same manner: 5 ^l of the appropriate dilution was spotted on the soft agar and incubated at 37°C for 24 h. Zones of inhibition of compounds were considered after subtraction of the inhibition zone of DMSO. Negative control (with no compound) was also observed.
RESULTS AND DISCUSSION
The analytical data suggest the formula ofmacrocyclic complexes as [M(C6H8N4O2)X2], where M = Co(II),
Ni(II), Cu(II), Zn(II), and Cd(II) and X = Cl-, NO-, and CH3COO-. The test for anions is positive only after
decomposing the complexes, indicating their presence inside the coordination sphere. Conductivity measurements in DMSO indicate them to be nonelectrolytic in nature [17] (10-20 Ohm-1 cm2 mol-1). Several attempts failed to obtain a single crystal suitable for X-ray crystallography. However, the analytical, spectroscopic, and magnetic data enable us to predict the possible structure of the synthesized complexes. All compounds give satisfactory elemental analyses results as shown in Table 1.
A close perusal of infrared spectra exhibit a pair of strong bands at ~3200 and ~3250 cm-1 corresponding to v(NH2), which is present in the spectrum ofsuccinyldihy-drazide but absent in the spectra of all the complexes [18]. However, a broad peak at ~3350-3400 cm-1 observed in the spectra ofall the complexes is due to the v(NH) stretching vibrations [19, 20]. A strong peak at ~1665 cm-1 in the spectrum of succinyldihydrazide is attributed due to the >C=O group of the -CONH moiety. This peak is shifted to a lower frequency (~1625-1640 cm-1) in the spectra of all the complexes [21], suggesting the coordination of oxygen ofthe amide group with metal. Further no strong absorption band was observed near 1710 cm-1 as in the spectrum ofglyoxal indicating the absence of the >C=O group of the glyoxal moiety. This confirms the condensation of the carbonyl group ofglyoxal and the amino group ofsuc-cinyldihydrazide [22, 23]. This fact is supported by the appearance of a new strong absorption band in the region —1590-1610 cm-1, which may be attributed to the v(C=N) stretching vibration [24, 25]. These results provide strong evidence for the formation of a macrocyclic fram
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