Cu(II)-bis(benzoylacetonate) complexes as potential inhibitors for tubulin polymerization: synthesis, crystal structure, spectral characterization, HSA, DFT, molecular docking studies, and antioxidant activity

The reaction of 1-phenyl-1,3-butanedione, also known as benzoylacetone (bzac), with adequate copper salts (sulfate/acetate) at a molar ratio of 2:1 in methanol led to two mononuclear complexes, trans-[Cu(bzac)(2)] (I) and cis-[Cu(bzac)(2)(CH3OH)] (II). Both complexes crystallize in the monoclinic P2(1)/c symmetry. The copper is four- and five-coordinate, exhibiting a square planar geometry and a distorted square-based pyramid in I and II, respectively. Their crystal structures form discrete supramolecular packing. Indeed, Hirshfeld surface analysis (HSA) with 2D fingerprint plots revealed short-range intermolecular contacts involving O-HOmicron hydrogen bonds and C-Hpi interactions in both complexes, in addition to pipi interactions in I. The complexes were characterized by IR and UV-Vis spectroscopic methods. Moreover, a thorough examination of I and II was conducted, focusing on their structural attributes, electronic characteristics, and both linear and nonlinear optical (NLO) responses through density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations. These quantum calculations were executed utilizing u omega wb97xd/6-311G**/SDD. The results revealed that the beta(0) value for II was approximately 23 times greater than that of urea. On the other hand, the static and dynamic second hyperpolarizabilities (gamma(0; 0,0,0), gamma(- 2 omega; omega,0,0), and gamma(- 2 omega; omega,omega,0)) of I are approximately 33% higher than those of II. From this, we infer that the complexes under investigation have potential as outstanding materials for second- and third-order NLO applications. The interactions of I and II with tubulin (PDB ID: 4O2B) were evaluated by molecular docking studies. The results showed that both complexes can bind to many sites on the target and may inhibit its polymerization process. Furthermore, the antioxidant activity of both complexes was also determined and fully discussed.