Dichloro-bis(theophylline)-copper(II) complex: Characterization of the physicochemical, computational pharmacokinetics, molecular docking, and cytotoxicity as potential antitumoral medicine

A dichloro-bis(theophylline)-copper(II) complex, named [Cu(theo) 2 Cl 2 ], was synthesized, with the aim to characterize its physicochemical and pharmacological properties. The complex was obtained by the slow evaporation method, and the experimental and theoretical physicochemical properties were studied using X-ray powder diffraction (XRPD), ultraviolet (UV–vis) spectroscopy, density functional theory (DFT), Hirshfeld surfaces, thermogravimetric (TG), differential thermal analysis (DTA), Fourier-transform infrared (FT-IR) and Raman spectroscopy. XRPD study confirmed that its crystallographic phase belongs to the monoclinic symmetry with C 2 / c ( C 2 h 6 ) space group. Important theoretical properties such as structural parameters, spin density, molecular frontier orbitals, chemical reactivity descriptors, and electrostatic potential maps were also predicted using the implicit solvation method in ethanol and water as solvents, and vacuum condition. Hirshfeld surfaces and crystal void analyses were employed to evaluate the intermolecular interactions and unit cell-free spaces. All Raman and FT-IR vibration bands were assigned with the aid of DFT studies. Thermal analyses revealed that the complex has thermodynamic stability between 293 K and ∼ 465 K. In addition, solubility was determined to evaluate the complex dissolution profile. Computational pharmacokinetic analysis revealed the topological polar surface area of 111.78 Å 2 , highlighting the potential of the developed complex for intestinal absorption, with low risk of hepatotoxicity and limited capacity to permeate the blood–brain barrier (BBB). Biological assays were carried out for the [Cu(theo) 2 Cl 2 ] complex, suggesting that it has antitumor activity against PC-3 (prostate), MDA-MB-231 (breast), and HCT-116 (colorectal) tumor cells, also indicating a half-maximum inhibitory concentration value near 4.93–5.11 mM. Finally, molecular docking studies were computed to evaluate the mechanism of interaction between the complex and deoxyribonucleic acid double-stranded.