Synthesis, characterization and study of antibacterial activity of enaminone complexes of zinc and iron

1 Introduction

Enaminones consist of an amino group linked by carbon–carbon double bond to a carbonyl group. The carbonyl group eases the preparation, isolation and storage of the complex, by providing required stability to the system. The chemistry of the enamino carbonyl group is an area of considerable scope (Montanile, 2003). Enaminones have received a large attention during last decade. Lot of work has been done to explore new routes for the synthesis of enaminones. Azzoro and his co-workers reported a simple method for the synthesis of enaminones by using amines and 1–3 diketones (Azzoro et al., 1981). In another method, β-chloro vinyl ketone was reacted with amines to synthesize enaminones (Pohland and Benson, 1966). Other methods of preparation include reactions between: formamide dimethyl acetates and ketones (Abdulla and Brinkmeye, 1979); acid chlorides with terminal alkynes and triethylamine (Karpov and Müller, 2003); primary amines and β-dicarbonyl compound catalyzed with copper nano-particles (Kidwai et al., 2009). Imada et al. (1996) has transformed β-amino ketones to enaminones using palladium. Lue and Greenhill (1996) functionalize enaminones by introducing different substituents on nitrogen, α-carbon and β-carbonylic carbon. These derivatives were used extensively, for preserving natural products and analogues.

Enaminones are important organic intermediates used to synthesize various heterocyclic and biologically active analogues. Naringrekar and Stella (1990) investigated the structural stability of enaminones and evaluated their ability as pro drugs of primary amines. Enaminone synthesized by acetyl acetone and diethyl amine was used as universal cation locating agent showing characteristic colors with different metals (Nasir et al., 1996). Eddington et al. (2000) reported synthesis and anticonvulsant evaluations of some enaminones. Enaminones have shown high p-glycoprotein affinity and can act as p-glycoprotein modulators (Salama et al., 2004). Zhuo (1998) studied the ¹⁷O NMR spectrums of primary and secondary enaminones.

In coordination chemistry, enaminones are considered “good chelating ligands” for transition metals. The anions produced from enaminone, offer potential isoelectronic alternatives to cyclopentadienyl-based anions and therefore, their transition metal complexes can act as possible alternative catalysts for olefinic polymerization (Markéta et al., 2006). A new ferrocene-containing enaminone [C₅H₅FeC₅H₄C(O)CH⚌C–(NHAr)CH₃] (Ar = 2-CH₃OC₆H₄) and its copper(II) complex has been synthesized and characterized by elemental analysis, ¹H NMR, IR, UV and X-ray crystallography (Shi et al., 2004).

The present work comprises the synthesis of complexes of 4-N,N-diethylamine-pent-3-ene-2-one [HL¹], 4-N,N-di n-propylamine-pent-3-ene-2-one [HL²] and 4-N,N-dicyclohexylamine-pent-3-ene-2-one [HL³] ligands with Fe(II) and Zn(II) ions. The ligands were synthesized using reported procedures (Nelson and Joe, 1959). Metal complexes were characterized by infrared, ultraviolet and atomic absorption spectroscopy. Ligands and their metal complexes were examined to assess their antibacterial activity using disc diffusion method.

2 Experimental work

3 Results and discussion

In our previous work, synthesis, characterization and antibacterial activity of several isomeric enaminones and their metal complexes with Ca(II) and Mg(II) have been reported (Tariq et al., 2009). In the present work, synthesis, characterization and antibacterial activity of three enaminones and their complexes with zinc and iron have been presented. Syntheses of the enaminones are represented in Schemes 1–3.

Close

Scheme 1

Synthesis of 4-N,N-diethylamine-pent-3-ene-2-one (HL¹).

Export to PPT

Close

Scheme 2

Synthesis of 4-N,N-diethylamine-pent-3-ene-2-one (HL²).

Export to PPT

Close

Scheme 3

Synthesis of 4-N,N-dicyclohexylamine-pent-3-ene-2-one (HL³).

Export to PPT

These enaminones can react with the Fe(II) and Zn(II) ions forming the neutral complexes. Preparation of enaminones involved the removal of water. Anhydrous sodium sulfate, sodium carbonate, anhydrous magnesium sulfate and p-toluene sulfonic acid were used as water removing agents. However, separation of p-toluene sulfonic acid from the reaction mixture was difficult in case of oily products. Water plays an important role as some enaminones were susceptible to hydrolysis by water. HL¹ (m.p = 105 °C) and HL³ (m.p = 154 °C) were colorless crystalline solids whereas HL² (b.p = 95 °C) was viscous liquor. The percentage of nitrogen in these ligands, determined by Kjeldahl’s methods, varies in the range 4.94–8.90%. These enaminone ligands were used to form complexes with Fe(II) and Zn(II). Most of these complexes were crystalline solids with shiny appearance and only few were amorphous solids. Their decomposition points were above 230 °C. Physicochemical characteristics of ligands and their metal complexes are listed in Table 1.

The solubility of the ligands and their complexes were tested in eight different solvents in both hot and cold states. All the ligands and the complexes were insoluble in n-hexane. Most of these were soluble in water and benzene. Details are given in Table 2.

The spectral data has been summarized in Table 3. The λ_max values are 310 nm, 310 nm and 290 nm for HL¹, HL² and HL³ respectively. Probable electronic transition is π–π*. λ_max values have shifted down after forming metal complex.

IR spectra of some enaminones or enamino ketones were reported by Dabrowski (1963). The IR spectra were recorded with nujol mull. Peaks of interest lay in the range 1572–1670 cm⁻¹ and 1427–1542 cm⁻¹. Some enaminone showed absorption at 1612–1620 cm⁻¹, as well. The IR data is given in the Table 4. Strong absorption bands for C–H stretch, C–H bend, C⚌C stretch, C⚌O stretch and C–N stretch are indicative of the formation of enaminones. These peaks were shifted to lower wave numbers after formation of metal complexes.

Metal to ligand ratio was calculated by finding out metal by atomic absorption spectrophotometer. By comparing these values, suitable geometries of these metal complexes were proposed. The ligand (HL¹, HL², and HL³) to Fe(II) ratio is 3:1. The synthesized complexes are proposed to show octahedral geometries. The ligand (HL¹, HL², and HL³) to Zn(II) ratio is 2:1. The synthesized complexes are proposed to show square planar geometries. The proposed structures of the complexes are shown in Figs. 1 and 2.

Close

Figure 1

Proposed geometry of the complexes of Fe(II) with HL¹, HL² and HL³, where R = ethyl, n-propyl, cyclohexyl.

Export to PPT

Close

Figure 2

Proposed geometry of the complexes of Zn(II) with HL¹, HL² and HL³, where R = ethyl, n-propyl, cyclohexyl.

Export to PPT

The antibacterial activities of the synthesized ligands and their metal complexes were tested against strains of bacteria, S. aureus and E. coli, using disc-diffusion method. All the three ligands were found to be quiet against both strains of bacteria. However, the metal complexes were active against bacterial strains. In general, the complex Zn(HL¹) has highest activity against the S. aureus and E. coli, showing that it has a good potential as bactericide. Fe(HL³) has shown good activity as well. The other complexes showed limited activity against S. aureus and E. coli bacteria. The Fe(HL¹) complex did not show any activity against the S. aureus. Results are depicted in Table 5.

4 Conclusion

Complexes of enaminones; 4-N,N-diethylamine-pent-3-ene-2-one [HL¹], 4-N,N-di n-propylamine-pent-3-ene-2-one [HL²] and 4-N,N-dicyclohexylamine-pent-3-ene-2-one [HL³] with Fe(II) and Zn(II) ions were synthesized. The complexes formed, were characterized by infrared, ultraviolet and atomic absorption spectroscopy. To evaluate anti bacterial character of complexes, these were tested against E. coli and S. aureus bacteria. It was found that complex Zn (HL¹) has significant action on both bacterial species while other complexes have normal antiseptic character.