Synthesis , Spectroscopic and Antimicrobial Studies of Transition Metal Complexes of N-Amino Quinolone Derivatives

In Iraq like most third world countries, attempts to discovered a new antibiotic drugs derived from coumarin and its metal complexes moreover develop the branch of applied in organic chemistry. Novel transition metal(II) complexes, [M(L1)2Cl2] and [M(L2)2Cl2], were synthesized from the reaction of MCl2.nH2O (M = Co, Ni, Cu) with (Z)-1-(1-(1H-indol-3-yl)ethylideneamino)quinolin-2(1H)-one (L1) or (E)-1-(2hydroxybenzylideneamino)quinolin-2(1H)-one (L2). The ligands were obtained from coumarin. N-amino quinoline-2-one (2) has been synthesized by the reflux of coumarin (1) with hydrazine hydrate in ethanol for 12 h. The azomethines (L1, L2) were prepared from the corresponding aryl carbonyls. The synthesized compounds were and characterized by element chemical analysis, molar conductance, magnetic susceptibility measurements, and spectral (electronic, and FT-IR) studies. The IR spectral data suggest the involvement of sulphur and azomethane nitrogen in coordination to the central metal ion. On the basis of spectral studies, an octahedral geometry has been assigned for all complexes. The free ligands and its metal complexes have been tested in vitro against a number of microorganisms in order to assess their antimicrobial properties.


Introduction:
Coumarins have stimulated extensive research in biology, organic chemistry and medicine, due to their antibiotic [1], anti-coagulant [2], anticancer [3], anti-inflamatory [4], and anti-HIV [5] properties.A number of natural or synthetic derivatives of coumarin have found pharmaceutical applications [6].Coumarins are nowadays an important group of organic compounds that are used as additives to food and cosmetics, [7] optical brightening agents [8] and dispersed uorescent and laser dyes.[9] The derivatives of coumarin usually occur as secondary metabolites present in seeds, roots and leaves of many plant species.Their function is far from clear, though suggestions include waste products, plant growth regulators, fungi stats and bacterio stats.[10] It is there-fore of utmost importance that the synthesis of coumarin and its derivatives should be achieved by a simple and effective method.The synthesis of this heterocyclic nucleus is of current interest.Coumarins have been synthesized by several methods including Von Pechman [11], Knovenagel [12], and Reformatsky [13] reactions.2-quinolone derivatives are found to be associated with various biological activities such as antitumor [14], antimalarial [15], antiplatelet [16], antidepressant [17], antiulcer [18], plant virucides [19], antifungal agents [20] , antioxidant activity [21] and herbicides [22] .Many substituted quinoline-2-one derivatives have recently craned great interest in chemotherapy as ant tumor drugs [23][24].Also a number of quinolones are excellent reservoir of bioactive substances [25].2-Quinolones are also valuable intermediates in organic synthesis, since they are easily converted into 2-chloro and then 2-amino-quinoline derivatives [26].Some Schiff bases bearing heterocyclic residues possess biological activities, such as analgesic, antiviral, antifungal and anticancer [27].Transition metals have varying utility and interesting chemistry.Coordination compounds are important due to their role in biological and chemical systems in various ways.It has been observed that metal complexes with appropriate ligands are chemically more significant and specific than the metal ions and original [28][29].

Materials and Method:
Melting points were determined on SMP40 melting point apparatus and were uncorrected.The IR spectra of the compounds were recorded on a shimadzu FT-IR-8300 spectrometer as KBr and CsI disks.The UV spectra were performed on Cintra-5-Gbes scientific equipment.Magnetic susceptibility measurement for complexes were obtained at room temperature using (Magnetic susceptibility Balance Model MSB-MKI).Flame atomic absorption of elemental analyzer, shimadzu AA-670 was used for metal determination.

Synthesis of Schiff bases:
A mixture of compound 1 (0.8 g, 0.005 mol) and the ( 0.005 mol) 2-hydroxybenzaldehyde (for L 1 ) or (0.0025 mol) of 1-(1H-indol-3-yl)ethanone was refluxed in absolute ethanol 25 ml for 6-8 hr.The reaction mixture was cooled and the product obtained was recrystallized from ethanol (Table 1 ) in (2:1) mole ratio ligand to metal respectively, with stirring.The mixture was heated under reflux for three hours, during this period, the precipitation was completed from, and collected by filtration, then washed with ethanol, and dried under vacuum for 4 hours.All these complexes were analyzed by using different available techniques, the physical proportion of the ligands and its metal complexes are listed in table (1).

Study of complexes formation in solution:
Complexes of ligands with metal ions were studied in solution using ethanol (or DMF) as solvents, in order to determine (M:L) ratio in the complex following molar ratio method [30].A series of solution were prepared having a constant concentration 10 -3 M of metal ion and ligands.The [M/L] ratio was determined from relationship between absorption of the absorbed light and mole ratio of [M/L].The results of complexes formation in ethanol were listed in table (1).

Antibacterial activity:
The antibacterial activity was estimated against Staphylococcus aureus, as gram positive and E.coli and Pseudomonas aersginosa as gram negative, and evaluated by using of agar disc diffusion method on the basis of the size of inhibition zone formed around the paper discs.For each concentration, the mean diameter (mm) of inhibition zone developed was calculated.The test compounds in measured quantities were dissolved in DMF to get concentrations of 200 and 100 ppm of compounds.Twenty five millileter nutrient agar media was poured in each Petri plates.After solidification, 0.1mL of test bacteria spread over the medium using a spreader.The discs of Whatmann no. 1 filter paper having the diameter 5.00 mm, were placed at four equidistant places at a distance of 2 cm from the center in the inoculated Petri plates.Filter paper disc treated with DMF served as control and Amoxyciline used as a standard drug.These Petri plates were kept in refrigerator for 24 hours for pre diffusion.Finally, Petri plates were incubated for 24 hours 30 o C. The zone of inhibition was calculated in millimeters carefully.

Results and Discussions
Schiff Bases Characterization: The Schiff bases, L 1 and L 2 are subjected to elemental analyses.The results of elemental analyses (C, H, N and S) with molecular formulae and melting points are presented in Table (1).
The results obtained are in good agreement with those calculated for the suggested formulae.The structures of the Schiff bases under study are given below in figure (1).The structures of these Schiff bases are also confirmed by IR spectra, which will be discussed later with metal complexes.

Characterization of the ligands and their complexes:
1. FT-IR: The FTIR spectrum (Table 2) of (Z)-1-(1-(1H-indol-3yl)ethylideneamino)quinolin-2(1H)-one (L 1 ) and (E)-1-(2hydroxybenzylideneamino)quinolin-2(1H)-one (L 2 ).The spectrum of ligand (L1) exhibited weak band at 3060 cm -1 , this could be attributed to ν(C-H) aromatic.A strong band at 1683 cm -1 which belongs to carbonyl and the other strong bands belong to the ν(C=N), ν(C=C) and ν(C-N) were found at 1585 cm -1 1572 cm -1 and 1244 cm -1 respectively, while the infrared spectra of the prepared complexes of (L 1 ) exhibited ν(C=N) in the range of 1569-1577 cm -1 which shows a shifting to the lower frequencies, it is which indicated the coordination of (L1) with metal ions through the nitrogen atoms in their structures.The spectra bands of complexes at 1668-1670 cm -1 were characterized for the carbonyl group which indicates that the oxygen atom of the carbonyl group was coordinated to the metal ion.The ligand (L 2 ) shows two moderately strong bands at 3200 and 1621cm -1 assigned as v O-H and v C=N groups.On complexes formation the former band shifts to lower energy while the phenolic O-H group disappears in the prepared complexes, this supports the deprotonation and linkage of O atom to the central metal ion [32].The stretching frequency at 1573 cm -1 can be attributed to C=C bond.A strong band appearing at 1681 cm -1 can be assigned to carbonyl group.A medium band at 1271 cm -1 may be assigned to C-N stretching vibrations.The absorption band in the range (471-535) and (423-465) cm -1 were assigned to (M-N) and (M-O) bands.The spectra bands of complexes at 1675-1679 cm -1 were characterized for the carbonyl group which did not suffer a shift.Thus, it is suggested that the oxygen atom of the carbonyl group is not coordinated to the metal ion.complexes are typically high spin complexes and having octahedral structure moreover the molar conductance of these complexes in DMF was 12.56, 14.12 ohm −1 cm 2 mol −1 (L 1 and L 2 complexes respectively) which shows that the chloride ions are coordinated to the cobalt (II) ion.The Ni(II) complexes exhibit the magnetic moment values in the range 2.7-3.3BM, indicating octahedral coordination moreover the molar conductance of these complexes in DMF was 11.00, 11.87 ohm −1 cm 2 mol −1 (L 1 and L 2 complexes respectively) which shows that the chloride ions are coordinated to the nickel (II) ion.The Cu(II) complexes exhibit magnetic moment in the range of 1.4-1.9BM indicating distorted octahedral nature for these complexes moreover the molar conductance of these complexes in DMF was 19.11, 17.32 ohm −1 cm 2 mol −1 (L 1 and L 2 complexes respectively) which shows that the chloride ions are coordinated to the coper (II) ion.Molar conductivity measurement in DMF solvent at 25ºC showed that the complexes were non-electrolyte.

The electronic spectra of light green Cobalt (II) complex (L 1 )
showed two spin allowed transitions at 17950, and 21610cm -1 assignable to T 1 g(F)→A 2 g(F) and 4 T1g(F)→ 4 T 2 g(P) transitions respectively, are in agreement with octahedral arrangements for Co(II) ion.

The electronic spectra of light green cobalt (II) complex (L 2 )
showed three spin allowed transitions at 14520,17000, and 22150cm -1 assignable to 4 T 2 g(F)→ 4 A 2 g, T 1 g(F)→A 2 g(F) and 4 T1g(F)→ 4 T 2 g(P) transitions respectively, are in agreement with octahedral arrangements for Co(II) ion.

The electronic spectra of yellow Ni (II) complex (L 1 ) showed
three spectral bands at 10500,16120 and 19800 assignable to 3 A 2 g → 3 T 2 g(F), 3 A 2 g(F) → 3 T 1 g(F) and 3 A 2 g(F) → 3 T 1 g(P) transition was in agreement with octahedral arrangements for Ni(II) ion.

The electronic spectra of light yellow Ni (II) complex (L 2 )
showed spectral band at 408 nm assignable to 3 T 1 g(F)→ 3 T 2 g(F) transition was in agreement with octahedral arrangements for Ni(II) ion.3.5.The electronic spectra of brown copper (II) complex (L 1 ) showed one spin allowed transitions at electronic spectrum of the Cu(II) complex assigned to E 2 g→ 2 T 2 g (34) transition which is in conformity with octahedral geometry.

The electronic spectra of dark green copper (II) complex (L 2 )
shows strong band at 287 nm which belongs to the charge transfer.The second band found in the visible region at 442 nm was attributed to the electronic transition E 2 g→ 2 T 2 g.

Stereo suggested structures of complexes:
According to the above mentioned data (spectra, molar conductance, molar ratio and magnetic properties), the proposed structures of completes were shown as below: Antibacterial activity: The Schiff base ligand was found to be biologically active.It is known that chelation tends to make ligands act as more powerful and potent bactericidal agent [35].The values indicate that the metal complexes had a higher antibacterial activity than the free ligand.Such increased activity of the metal complexes can be explained on the basis of the overtone concept [36] and chelation theory.[37] According to the overtone concept of cell permeability, the lipid membrane that surrounds the cell favors the passage of only lipid soluble materials, due to which liposolubility is an important factor controlling the antimicrobial activity.On chelation, the polarity of the metal ion is reduced to a great extent due to the overlap of the ligand orbital and the partial sharing of the positive charge of the metal ion with donor groups.Furthermore, it increases the delocalization of electrons over the whole chelate ring and enhances the lipophilicity of the complex.This increased lipophilicity enhances the penetration of the complex into the lipid membrane and blocks the metal binding sites on the enzymes of the microorganism.
Antibacterial activity was leads to the following conclusions: 1.The metal complexes show more activity than the ligands against tested bactria.2. Antibacterial activity of Cu(II) complexes have higher activity than the other complexes. ).

Structure of the Schiff Base Complexes:
The isolated complexes of Co(II), Ni(II) and Cu(II), ions with the Schiff base ligand L 1 and those of Co(II), Ni(II) and Cu(II), with the Schiff base ligand L 2 were subjected to elemental analyses (C, H, N and metal content), IR, magnetic studies, molar conductance to elucidate their molecular structures.Elemental analysis of the ligands and its metal complexes are reported in Table1.The elemental analysis data agreed well with the proposed formulae for the ligands and metal complexes.The solubility of the complexes of ligands was studied in various solvents.The complexes are soluble in DMSO and DMF while insoluble in common solvents such as ether, chloroform, and carbon tetrachloride.

Table 1 :
Physico analytical data for the ligands and metal complexes.

Table 2 :
The FT-IR spectral data for the ligands and metal complexes.
2. Magnetic susceptibility and conductivity measurements: Co(II)complexes are in the range of 4.7-5.1 BM indicating that the Co(II)

Table 3 .
CompoundAntibactrial activity of legands and metal complexes The zone of inhibition was measured in mm (Concentration in ppm)