RESEARCH

I work in the area of theoretical chemistry, which can be defined, as the application of quantum and classical theories to the description of chemistry. The increase in the performance of computers has lead to an accurate modelization of various chemical phenomena. For instance, the energetic requirements for a given reaction can be calculated with reasonable degree of accuracy, or the stability of computer-designed molecules can be predicted, even before they are actually synthetized. Due to this tremedeous potential, computational/theoretical chemistry has given rise to a new branch inside chemistry studies with increasing impact in our way of doing science.

Hydrolysis of phosphodiester bonds are of central importance to biology, since DNA and RNA have phosphate diester as the links between the various nucleotides. The study and characterization of the mechanism for the hydrolysis of this type of bonds is thus central to the understanding of the degradation of proteins, DNA and RNA. I began the study of the hydrolysis of phosphates. An important effort of this project is to determine how the environment (solvent or enzyme) affects the reaction mechanism. Two kind of methods are employed for that, dielectric continuum methods and QM/MM methods in which the reactive part of the system is decribed by quantum mechanical methods and the "non-reactive" part by simpler Molecular Mechanical models. These projects are being carried out in collaboration with Prof. Martin Karplus and Prof. A. Dejaegere at Universite Louis Pasteur (Strasbourg, France) and Prof. Darrin M. York at University of Minnesota (Minneapolis, USA). For more details, please look at these publications:

• "Mechanism of Alkaline Hydrolysis of Cyclic and Acyclic Sulfates: An ab Initio Study with Solvation Correction"; X. Lopez, A. Dejaegere and M. Karplus; J. Am. Chem. Soc., 1999, 121, 5548-5558.


• "Solvent Effects on the Reaction Coordinate of the Hydrolysis of Phosphates and Sulfates: Applicaqtion of Hammond and Anti-Hammond Postulates to Understand Hydrolysis in Solution"; X. Lopez, A. Dejaegere and M. Karplus; J. Am. Chem. Soc., 2001, 123, 11755-11763.


• "Theoretical Studies on the Hydrolysis of Phosphate Diesters in the Gas Phase, Solution and RNase A."; Int. J. of Quantum Chemistry, 2002, 86, 10-26.


• "Theoretical Evaluation of pKa in Phosphoranes: Implications for Phosphate Ester Hydrolysis"; X. Lopez, M. Schaefer, A. Dejaegere and M. Karplus, J. Am. Chem. Soc., 2002, 124, 5010-5018.


• "Hybrid QM/MM Study of Thio Effects in Transphosphorylation Reactions", B.A. Gregersen and X. Lopez and D.M. York, Journal of the American Chemical Society, 2003, 125, 7178-7179.