Synthesis Characterization and Biological Sciences of Some Novel Schiff Base Derivatives of Ferrocence and Their Metal Complexes

Abstract

Focus of this research work is on the synthesis and biological studies of ferrocenyl thiosemicarbazones and their transition metal complexes. Two series of Schiff’s base derivatives of acetylferrocene (58-71 & 87-101) were synthesized by the condensation of acetylferrocene with appropriate benzylthiosemicarbazides (44-57) and phenylthiosemicarbazides (72-86) in ethanol under the catalysis of acetic acid. All these compounds were fully characterized by IR, 1H NMR, 13CNMR spectroscopic and EIMS spectrometric data. Crystallographically studies of ferrocene-based thiosemicarbazones have been conducted in order to investigate the prevalence of the thioamide dimersynthon and carbon bonding. All the compounds have shown a general preference for the adoption of the cis, trans conformation about the central thiourea moiety which is ideal for the formation of a dimeric hydrogen-bonded {···H–N–C=S}2 synthon as the building block. This dimeric synthon is observed in all the compounds, with the methyl group particularly set for playing its supportive stabilization role through C-H···S and carbon bonding interactions. The structural features and ground state geometry calculations have been computed at B3LYP/6- 31G** (LANL2DZ) level of theory. The computed geometrical parameters, bond lengths, bond angles and dihedral angles are in reasonable agreement with the X-ray crystallographic data. We shed light on the frontier molecular orbitals; highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and HOMO-LUMO energy gaps. The intra-molecular charge transfer (ICT) was observed in all the studied compounds. The excited state geometries have been optimized by using the time-dependent DFT. Metal complexes of benzylthiosemicarbazones (102-127) were prepared by reacting with metal salts (CuCl2, CoCl2, Zn(acetate)2 and Ni(acetate)2) with benzylthiosemicarbazones in 1 : 2 ratio respectively. All the complexes were characterized by IR, UV-Vis, Molar conductance and Magnetic moment. Crystal structure of Co(II) (120) complexe was grown and characterized to confirm the structure and geometry of metal complexes. The crystallographic data confirmed the tetrahedral geometry of synthesized metal complexes. The synthesized thiosemicarbazones and their metal complexes (58-127) were tested against acetylcholenesterase (AChE), butyrylcholinesterase (BChE), alpha glucosidase, lipoxygenase (LOX) and antioxidant activities. In general, all newly synthesized metal complexes (102- 127) showed higher inhibitory activities than their respective ligands. The Cu(II) complex (102) was found to be the most potent against acetylcholenesterase as well as butyrylcholenesterase having IC50 values 9.21±0.29 μM and 12.70±0.27μM respectively while its ligand was in active. For alpha glucosidase activity, the metal complex (106) was highly active with IC50 value 0.8±0.19μM (%inhibition= 99.92±0.21) while its respective ligand did not show considerable activity (% inhibition 15.71±0.66). Similar behavior was observed for lipoxygenase (LOX) enzyme where compound (122) was most active (IC50 = 15.02±0.0 μM, % inhibition = 93.58±1.21) while its ligand was inactive. The Co(II) complex (121) showed moderate DPPH radical scavenging activity with % inhibition of 83.74±0.96 (IC50 = 169.67±0.75μM). High biological activities of metal complexes as compared to their respective ligands highlighted the importance of complexation. The studies show the importance of new class of thiosemicarbazones and their metal complexes that enhanced their biological interest.