Modelagem computacional de sistemas de liberação controlada de complexos de platina(II) com atividade antitumoral formados por nanocompostos de carbono

Abstract

In this work, a quantum chemical investigation was performed to study the inclusion complexes formation between a carbon nanohorn (NH) and nanotube (CNT) structures with cisplatin (cDDP) and its derivative dinuclear platinum(II) or bis(platinum) (bisPt) molecules,using the density functional theory (DFT) with the B3LYP functional and 6-31G(d,p)/LANL2DZ standard basis sets. The inclusion of the drugs in host molecules such as CNH and CNT, aims to reduce the toxicity and enhance the effectiveness of cisplatin. The search for minimum energy structures on the potential energy curve (PEC) for NH-cDDP andCNT-cDDP interactions were carried out, and then calculated the stabilization energy and NMR spectra, which can be of great aid for experimental identification of the inclusion compound.Our results indicated that the NH and CNT with cDDP can indeed form stable inclusion complex, with the calculated 1H NMR and 15NMR chemical shifts for cDDP atoms revealing very substantial changes due to complex formation (~20 ppm) that can be easily experimentallyobserved, which is helpful to the spectra assignment and the inclusion compounds structural elucidation. For the formation of bisPt@NH inclusion complexes, initially, the influence of the conformational arrangement of the 1,4-diaminebutane spacer chain was performed before idealize the bis(platinum) molecules. Our results show that all seven bisPt@NH inclusion complexes formed are stable, and as well as for the cDDP@NH complexes, the stabilization energy BSSE corrected, provides a more realistic of the stabilization of the complexes. TheChelpG charge analysis indicates that the electrostatic interactions are probably dominant to stabilize the inclusion complexes. Finally, the first results of the oxidized carbon nanohorn and nanotube (NHox and CNTox, respectively) were shown. The oxidizing topologies were builtand the influence of the organic groups amount presents on the cap and tubular region of CNTox and CNCox were evaluated in the structure-stability relationship of these nanostructures.