Synthesis, Characterization and Biological Studies of Some Novel Mannich Bases and Their Transition Metal Complexes.

Abstract

The present study was carried to synthesize some novel Mannich bases and their transition metal complexes. The ligands were synthesized by condensing various aldehydes and amines with cyclopentanone and cyclohexanone in presence of calcium chloride as a catalyst. All the reactions were carried out by using ethanol as solvent. The progresses of the reactions were monitored with the help of TLC. The synthesized scaffolds were then complexed with various transition metal chlorides such as CuCl2, NiCl2, CoCl2, and FeCl2 to afford their respective complexes. FTIR, 1H NMR, 13C NMR, UV-Vis, TGA and MS techniques were used to characterize the ligands and their complexes. The AAS was applied to propose the geometries of the synthesized scaffolds by means of metal-ligand ratio. The synthesized compounds were analyzed for their antiurease as well as antibacterial potentials. The nature of SAR of synthesized scaffolds has been demonstrated using docking studies. Twenty one new scaffolds are synthesized and characterized. The compound (1) was derived by condensing 4-methoxybenzaldehyde and pyrrolidine with cyclohexanone in ethanol. One equivalent of calcium chloride was applied as a catalyst. Ice cold conditions are obeyed in the beginning of reaction .The further development of the reaction was carried out at 70-90 oC for about 1.5 hour followed by continuous stirring. The further stirring was continued for one hour at room temperature. TLC was applied as a monitoring tool for the progress of the reaction. The precipitation of the product was carried out by the addition of the 5% NaHCO3. The compound (1) was finally obtained by filtration and washing. The compound (2) was obtained by the condensation of 3, 4-dimethoxybenzaldehyde, pyrrolidine and Cyclohexanone in ethanol under the same conditions as applied for compound (1). The same strategy was applied for the production of compound (3). It was obtained by the condensation of 4fluorobenzaldehyde, aniline and cyclopentanone.The Mannich reaction of 3,4dimethoxybenzaldehyde, pyrrolidine and cyclopentanone in the presence of calcium chloride using ethanol as a solvent to produce a novel Mannich base (4). The same strategy was applied for the isolation of the above mentioned scaffolds, (2), (3) and (4) as for compound (1). The complexes of the synthesized ligands were obtained by their reaction with transition metal salts. The compound (5) was obtained by mixing of equimolar ethanolic solutions of (1) and copper (II) chloride followed by heating at 50 oC for 10 minutes. The constant stirring of contents for three hours at room temperature resulted in the precipitation of (5). Finally the compound (5) was obtained by evaporating the solvent and washing with distilled water. The compound (6), (7), and (8) were derived by reacting compound (1) with nickel (II) chloride, cobalt (II) chloride and iron (II) chloride respectively. The compounds (9), (10), (11) and (12) were synthesized by reacting copper (II) chloride, nickel (II) chloride, cobalt (II) chloride and iron (II) chloride with compound (2) respectively. The complexation of the compound (3) with copper (II) chloride, nickel (II) chloride, cobalt (II) chloride zinc (II) chloride and iron (II) chloride resulted in the production of compounds (13), (14), (15), (16) and (17) respectively. The compounds (18), (19), (20) and (21) were produced by the reaction of copper (II) chloride, nickel (II) chloride, cobalt (II) chloride and iron (II) chloride with compound (4). All the complexes were isolated in similar fashion as compound (5). All the synthesized scaffolds were examined for their antiurease potential. It was revealed that all synthesized analogs exhibit moderate to excellent antiurease character as compared to standard thiourea with IC50 value, 21.25± 0.15 µM. The potent antiurease potential was reflected by compound (3) with IC50 value (0.83± 0.002 µM) which was greater than standard. Similarly the compounds (19) with IC50 value 1.42 ± 0.003 µM, (6) with IC50 value 4.41±0.003, (8) with IC50 value 5.21±0.003 μM, (21) with IC50 value 5.41 ± 0.005 µM, (11) with IC50 value 5.82 ±0.007 μM, (4) with IC50 value 9.25 ± 0.002μM and (9) with IC50 value 16.87± 0.03 µM exhibit better antiurease potential even than standard thiourea with IC50 value, 21.25± 0.15 µM. The synthesized scaffolds were also evaluated for their bactericidal behavior in comparison with standard drug Gentamicin. The investigative data reveals that synthesized scaffolds exhibit moderate to good bactericidal potential.