REACTIVE MD · Reactive molecular dynamics for Organometallic reactions relevant to asymmetric hydrogenation reactions
6РП — Действия „Мария Кюри“
- Период
- 2007-02-01 → 2008-12-31
- Финансиране от ЕС
- 185 155 €
- Участници
- 1
- Схема
- IIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Методи за компютърно симулиране на органометални катализатори помагат да се предвиди коя конфигурация на молекулата е най-стабилна. Това улеснява синтеза на чисти лекарства и природни съединения, като спестява време и разходи за скъпи лабораторни опити.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - REACTIVE MD (Reactive molecular dynamics for Organometallic reactions relevant to asymmetric hydrogenation reactions)
Asymmetric hydrogenation is a very useful chemical reaction for the synthesis of pharmaceuticals and natural products in an enantiopure form; that is, without being contaminated by the mirror image of the desired compound, which in the best case represents a 50 % waste, and in the worst case can have undesirable biological activity such as side effects. However, this reaction depends on the availability of a suitable catalyst. Catalysts are usually organometallic compounds (molecules containing bonds between carbon and a metal atom), but they all have a limited scope and it is very difficult to predict which catalyst will be best for a given reaction without carrying out expensive experiments. The goal of this project was to develop efficient theoretical methods that can eventually be used to predict the selectivity of a catalyst by means of computer simulations, thus saving time and effort. A key part of this process is to be able to calculate the energies of the many possible intermediate species that are involved in the reaction. While there are methods based on quantum mechanics that are often used for this purpose, such methods have practical limitations because they are slow and expensive to use. We developed a method based on molecular mechanics, a much faster approach, by incorporating a function based on atomic orbital overlap that accounts for the 'trans influence', a remarkable electronic interaction between atoms bound on opposite sides of a metal atom. By adjusting the parameters in our function to best fit a set of reference data obtained from quantum mechanics on small molecules, we were able to develop a method that can predict which configuration of an organometallic compound will be most stable, even for large molecules, within a timeframe of seconds using a typical desktop computer. For comparison, quantum mechanical methods on similar molecules can take days and may require a supercomputer. Our method can be incorporated into sophisticated simulations of reactions in solution, and promises to become a powerful tool for the study of chemical reactions involving organometallic compounds.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Asymmetric catalytic hydrogenation is a reaction of great interest in total organic synthesis and with valuable applications in the pharmaceutical industry. This project will apply and extend recent developments in the state-of-the art for reactive force fields and reactive molecular dynamics (MD) to the simulation of iridium-catalyzed asymmetric hydrogenation reactions recently developed by Pfaltz and co-workers at Basel. The initial step will be the parameterization of the ReaxFF force field for iridium, based on a library of DFT structures and energies for a variety of conformations and transition structures, based on Pfaltz's asymmetric hydrogenation phosphinooxazoline (PHOX) catalysts. Once the force field is ready, it will be used for running extensive conformational searches using Monte Carlo and molecular dynamics methods, for a variety of ligands and substrates; the most promising structures will be refined using more accurate DFT methods. This will be followed by reactive MD simulations of the react ion process itself, with inclusion of solvent effects. The result will be a detailed understanding of the reaction mechanism, and will ultimately facilitate the screening of new ligands and substrates for the hydrogenation reaction. The project will involve a close collaboration with Prof. Pfaltz, who will provide additional experimental data for calibrating and testing the methods, and who can test our predictions.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY OF BASEL · BASELКоординаторНиво градШвейцария
Връзки
Данни: CORDIS, © Европейски съюз