New copper(II) and nickel(II) complexes derived from ONO-donor tridentate Schiff base ligands and 1-methyl imidazole as co ligand for their use as antidiabetes and antioxidants: synthesis, crystal structures, DFT computational and in vitro studies

Copper(II) and nickel(II) complexes derived from tridentate ( ONO ) Schiff base ligands namely 5-(diethylamino)-2-(((2-hydroxy-4-nitrophenyl)imino)methyl)phenol ( L1 ) and 5-chloro-2-((4-(diethylamino)-2-hydroxybenzylidene)amino)phenol ( L2 ) together with 1-methyl imidazole ( MeIm ) as auxiliary ligand have been synthesized. The complexes have molecular formula [Ni( L1 )( MeIm )] ( 1 ), [Ni( L2 )( MeIm )] ( 2 ), [Cu( L1 )( MeIm )] ( 3 ), and [Cu( L2 )( MeIm )] ( 4 ). They were elucidated using spectroscopic techniques and their purity was confirmed by elemental analysis. Single X-ray crystallography analysis for 1 – 3 revealed that the copper(II) and nickel(II) are four-coordinated to one azomethine nitrogen atom, two oxygen atoms from L1/L2 and one nitrogen atom from MeIm conforming to a slightly distorted square planar geometry. Density functional theory studies revealed that, 1 exhibits the smallest energy band gap (6.552 eV), suggesting it to be the most chemically reactive among the four complexes while 4 with energy band gap of 7.754 eV is suggested to be the most stable. All the complexes displayed good α-glucosidase inhibition activity and even outshined acarbose, the reference drug used for this study. Complex 3 , with an IC 50 value of 14.19 mM showed the highest α-glucosidase inhibition ability while acarbose with an IC 50 value of 17.98 mM displayed the least activity. Complexes 1 – 4 as well as acarbose, only inhibit α-amylase at concentrations >100 mM at the experimental conditions for this assay. Complexes 1 – 4 exhibited good NO • radical scavenging ability and complex 1 with an IC 50 value of 17.98 mM showing the highest activity while quercetin with an IC 50 value of >100.00 mM showing the least activity. For the DPPH assay, complex 1 with an IC 50 value of 28.75 mM has the highest DPPH free radical scavenging ability followed by 4 , 3 and 2 , however, none of them performed better than quercetin. The complexes predicted physicochemical and pharmacokinetic parameters complied with Lipinski's Ro5. • Two nickel(II) complexes and two copper(II) complexes are successfully synthesized and characterized. • The crystal structures of three complexes are reported and they conform to a distorted square planar geometry. • All the complexes inhibit α-glucosidase better than acarbose. • All the complexes scavenge nitric oxide radical better than quercetin. • Quantum chemical descriptors of the complexes were determined to probe their electronic and chemical reactivity. • The complexes predicted physicochemical and pharmacokinetic parameters comply with Lipinski's Ro5.