Síntese e caracterizações do complexo Cu(teofilina)(H2O)2Cl2] para aplicação antitumoral

Abstract

Cancer is a disease that can affect any part of the body and spread rapidly. In 2022, around 10 million people were victims of this disease, and existing therapies for its treatment have their limits. In this context, coordination compounds are gaining increasing attention due to their specific interactions with DNA and their potential to cause DNA damage in tumor cells. Despite the publication of the structural description of the [Cu(theophylline)(H2O)2Cl2] complex, further studies on its physicochemical and biological properties are required. Therefore, this work deals with the synthesis and characterization of the structural, optical, thermal and vibrational properties as well as the cellular viability of the complex. The synthesis method used to grow the crystals was a slow evaporation of the solvent, which made it possible to obtain the crystals in 8 days. Subsequently, the material was characterized by X-ray diffraction (XRD), Rietveld refinement, thermogravimetric analysis (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), UV-Vis optical absorption spectroscopy, Raman and Fourier transform infrared (FTIR). In addition, calculations based on density functional theory (DFT) were performed to reliably assign the bands observed in the experimental spectra and to obtain electronic information about the complex. In addition, cell viability assays were performed on tumor and healthy lines to confirm the in vitro assays and molecular docking assays were performed. XRD and Rietveld refinement showed that the sample crystallized in the triclinic system, space group P1 ̅ (Ci 1) with two formulas per unit cell (Z= 2) and the following lattice parameters, a = 9.926(5) Å, b = 9.991(5) Å, c = 7.478(4) Å, α = 123.1(4)º, β = 94.4(4)º and γ = 83.8(5)º. Thermal analysis showed the thermal stability of the material up to 358 K. Optical UV-Vis absorption spectroscopy was used to evaluate the d-d transition due to the presence of Cu(II). DFT was used to determine the optimized geometry of the complex, the map of the electrostatic potential, the spatial distribution and energy of the HOMO and LUMO orbitals, chemical reactivity descriptors and thermodynamic parameters. Bands related to the vibrational modes of the groups present in the complex were observed by Raman spectroscopy and FTIR and assigned using DFT calculations. Cell viability assays were used to verify the dose-dependent activity against tumor lines and to calculate IC50 values and selectivity indices for each cell line. Molecular docking showed the regions of interaction of the complex with DNA and BSA as well as the energy values resulting from these interactions. The data obtained indicate that the complex studied has good potential for use as an antitumor agent.