New Bioactive Homoleptic and Heteroleptic Cu(II) Carboxylates

Abstract

There is a dire need in modern era of scientific research, to discover new metal based drugs with higher activity and selectivity to cope with the impending challenges in treating diseases like diabetes, alzheimer and cancer. In this regard, metal complexes derived from biologically essential metal like copper with strong history of biological activities are exciting candidates to be considered. This thesis reports the synthesis, characterization and biological activities of five series of homoleptic and heteroleptic Cu(II) complexes (5×7=35). Different derivatives of phenylacetic acids (2-chloro, 3- chloro, 2-methyl-3-nitro, 2-methoxy and 2-bromo) were reacted in aqueous medium with the metal salt CuSO4.5H2O to yield five (1-5) new homoleptic metal complexes. Further, reacting these complexes with pyridine based compounds (Pyridine, 1,10- phenenthroline, 2,2’-bipyridine, 2-chloropyridine, 2-bromo-pyridine, 3-methylpyridine) generated five series of new heteroleptic metal complexes. A total of twenty crystal structures were determined throughout this work by single crystal XRD analysis. The multi binding mode of phenylacetic acids used in the study gave rise to different molecular arrangements ranging from monomer to dimer, oxygen bridged or paddlewheel conformations. In almost all crystal lattices distorted square pyramidal geometry was found around the metal center. The DNA binding ability of the synthesized complexes was tested through UV-visible spectroscopy and the binding constant (Kb) was calculated for each complex along with ΔG values. Results of the study suggested that all these complexes bind with Salmon-sperm DNA through a mixed binding mode both intercalative and groove binding. In order to evaluate the other therapeutic applications of the complexes, an in-vitro enzyme inhibition assay was performed. The enzyme inhibition potential was tested for two classes of enzymes, α-glucosidases and anticholinesterases which are considered for diabetes and Alzheimer, respectively in humans with acarbose and galantaminehydrobromide as control. Their enzyme inhibition abilities were further correlated with the structural features of the synthesized complexes. All data suggested that such complexes could provide a potential solid foundation in future for designing Cu-based drugs to treat type (II) diabetes and Alzheimer disease.