Skip to main content

Ab initio Statics and Molecular Dynamics Simulation of Olefin Metathesis Catalysts for pharmacological purposes

Article Category

Article available in the folowing languages:

New drugs and more by catalysis

Many large organic molecules can be modified by catalytic reactions to produce new molecular arrangements, predicted by computer simulation to have useful biological properties or other applications.


Olefin metathesis is an organic reaction that redistributes fragments of alkenes (olefins) by the scission and regeneration of carbon-carbon double bonds. Catalysts for this reaction have evolved rapidly over the past few decades. Because of the relative simplicity of olefin metathesis, it often creates fewer undesired by-products and hazardous wastes than other organic reactions. The project COMPUTEDRUG (Ab initio statics and molecular dynamics simulation of olefin metathesis catalysts for pharmacological purposes) has given computational insight into the olefin metathesis family of catalysts, leading to the proposition of a new generation of drugs with superior activation properties, cost and stability. Project members concentrated on better understanding the role of olefin metathesis catalysts and then determining how the catalysts are activated. Using steric maps, it is possible to predict which architecture the olefin metathesis catalyst must adopt, corresponding to each alkene substrate. Relative stability of the metallacycle has been found to be critical. When this intermediate is energetically disfavoured, the olefin metathesis catalytic reaction does not take place under normal conditions. This understanding has allowed the prediction of a new generation of catalysts, by replacing ruthenium with the non-toxic and cheaper iron, and substitution of the N-heterocyclic carbene ligand by a second ylidene ligand. The activation of olefin metathesis catalysts has provided an estimate of the value of each catalyst. Just the relative stability between the so-called central metallacycle intermediate and its precedent coordination intermediate is enough to predict if an olefin metathesis proceeds. Careful study of deactivation processes has helped to determine which kinds of substitutions are not suitable for olefin metathesis catalysis, because the resulting catalyst would be unstable and decomposes. Studying the rate-determining step of the decomposition reactions is enough to indicate if they will be competitive with the regular olefin metathesis reaction. Computer simulations are now often enough to test a new molecule, and compare its activity with existing catalysts, saving experimental resources and the syntheses of hundreds of candidate catalysts that would be inactive. Improving the synthesis of drugs containing a macrocycle will have immediate applications, notably in the treatment of hepatitis. In addition to pharmacology, the new techniques will be useful across a range of other activities, including gold catalysis, carbon dioxide fixation and hydrogenation.


Catalysis, olefin, olefin metathesis, COMPUTEDRUG, metallacycle, pharmacology

Discover other articles in the same domain of application