Simulations atomistiques de la fonctionnalisation des nanotubes de carbone par des derives du biguanide et de l’uracile

Abstract

The main objective of this thesis is the development and study of new advanced hybrid nanostructures for applications in nano-medicine (targeted transfer and therapy) and nanotechnology (electronic and non-linear applications). This research work is carried out by atomistic simulations using quantum modeling methods (density functional theory, DFT) and the ONIOM method (hybrid modeling method, quantum mechanics/molecular mechanics). We first studied nanomaterials modeled by the functionalization of two biguanide derivatives (metformin and buformin) at the end of the single-walled carbon nanotubes SWCNT(5,5) via acylchloride. Next, we functionalized two uracil derivatives (5-fluorouracil and 1-(2-hydroxyethyl)-5-fluorouracil) on the wall of the single-walled carbon nanotubes SWCNT(5,5) via 1,3-dipolar cycloaddition of azomethine ylide. The results of the reaction energies, binding energies, vibrational analyses and thermodynamic properties show that these modeled nanometric molecular structures are stable and can be synthesized. The values of Gibbs free energies of solvation show that their dissolution in water is thermodynamically favorable and their degree of dissolution is greater than those of the biguanide and uracil derivatives; this favors the nano-delivery of these nanomaterials. The results obtained from energy gaps and non-linear responses especially the hyperpolarizabilities reveal that these nanomaterials are promising materials for non-linear and electronic applications. These nanostructures are highly reactive and electrophile. Finally, we carried out a more precise study in gas phase and aqueous solution of the therapeutic molecule 1-(2-hydroxyethyl) 5-fluorouracil and the prediction of its encapsulation in capped carbon nanotubes. This molecule is more soluble in water and more reactive than the 5-fluorouracil (5-FU) molecule, which is a well-known anticancer molecule in the pharmaceutical industry. The analysis of the structural and thermodynamic properties predicts that this therapeutic molecule can be encapsuled in carbon nanotubes. The results obtained in aqueous solution show that solvation has effects on all the properties of these modeled molecular structures.