Computational studies on supramolecular hydrogen-bonded structuresfrom nanocapsules to proteins

Resumen

of the thesis entitled: Computational studies on supramolecular hydrogen-bonded structures: from nanocapsules to proteins.In this thesis different methods were used to study several systems in which the hydrogen bond has a key role. The validity of the theoretical methods applied was always contrasted with the experimental evidences available from the group of Prof. Javier de Mendoza in the context of an intense collaboration in the Institute of Chemical Research of Catalonia (ICIQ). In certain cases the theoretical results provided an explanation to experimental observations and in other cases they had the prediction as main objective. In Chapter II the general concepts of the Density Functional Theory (DFT) and of the Molecular Mechanics (MM) are described, emphasizing the specific methods used in the thesis.In Chapter III a DFT study is presented on the dimerization of the 2-ureidopyrimidone (UPy), and also on the tautomeric equilibrium established from this molecule. The influence of the substituent in position 6 of the pyrimidinone ring and the solvent effects were explained.Chapter IV deals with systems also based in dimers of ureidopyrimidone, but much larger. A molecule is described, composed of 3 UPy moieties bound to a cyclotriveratrylene unit, which self-assembles leading to the formation of a nanocapsule able to trap fullerenes inside. The nanocapsule shows higher affinity for certain fullerenes. The viability of the complexes (CTV-3UPy)2Cn(n=60,70,76,78,84,90) was studied as well as the preferences of the host. The aim was giving an explanation to experimental results obtained with C60 and C70 and predicting selectivity for higher fullerenes.Chapter V presents a Molecular Dynamics study on the effect of the punctual mutation R337H in the stability of the tetramerization domain of the protein p53 (p53TD). It has been experimentally demonstrated that this mutation prevents the protein from carrying out its normal function as a tumour suppressor. The simulations allowed explaining the disruption process suffered by the mutant protein.Using the same methods as in the previous chapter, chapter VI presents a study on the interaction of several ligands with the surface of the wild type protein (p53TD) and the mutant protein (R337H p53TD). The ligands tested were of the oligoguanidinium type and tetraguanidilated calix[4]arenes. The calixarenes proved to stabilize the structure of the mutant protein, maintaining it in a conformation similar to that of the wild type protein. Chapter VII describes the study, by means of Molecular Dynamics, of the unspecific interaction between a DNA molecule and undecaguanidinium ligands. The simulations proved that the ligands have high affinity for the DNA. In Chapter VIII the conclusions of the overall thesis are summarized.Resumen de la tesis doctoral titulada: Computational studies on supramolecular hydrogen-bonded structures: from nanocapsules to proteins.