About our Research

The main objective of our research is the development of new catalytic processes. We try to achieve this by studying the relationship between the structure of the catalyst and its performance in catalysis. Our main research interest is in the field of homogeneous catalysis with the aid of transition metal complexes and a broad range of catalytic reactions has been studied. The major activity is in the field of ligand synthesis based on phosphorus donor atoms by rational design assisted by molecular modelling. Ligand design is supported by thorough mechanistic (in-situ) studies of catalytic reactions to acquire insight in structure-activity relations. Besides the study of well-known steric and electronic ligand effects the influence of ligand geometries around the metal centre is a key issue in this research. For example, catalytic reactions can be accelerated by forcing the geometry of the “catalyst” towards a structure that resembles the transition state, as has been proposed for metalloenzymes. This has resulted in novel, very active and (enantio)selective catalysts.

A: Rational design of diphosphorus ligands – a route to superior catalysts

This project focuses on homogeneous catalysis using (chiral) bidentate ligands that enforce "unusual" geometry's. New bidentate ligands have been designed that force the geometry of the starting complex towards a structure that resembles the transition state. This way the course and rate of catalytic reactions can be directed. Furthermore, the rate and selectivity of an elementary step of a catalytic cycle can be steered by influencing the structure of the initial or product complex. This has been successfully applied in studies of the fundamental aspects of the rhodium-catalysed hydroformylation. The aim is to get more detailed information about the mechanism of a new generation of catalysts based on wide bite angle enforcing ligands. Especially the relation between catalyst structure and selectivity of the reaction is investigated. Asymmetric hydroformylation catalysts based on rhodium and P-chiral phosphine ligands have been developed. The newly developed ligands have been applied in a wide variety of metal complexes leading also to novel palladium and nickel catalysts. A variety of palladium catalysed reactions are being studied which are important in organic synthesis: cross-coupling, allylic substitution, Heck reaction, and carbonylation. Ligand effects and kinetics are key issues in these projects.

See also our publication list

B: Development of highly efficient catalysts for sustainablebiomass conversions

The goal of a sustainable society requires the efficient use of renewable or sustainable materials and demands the development of selective new methodologies for the preparation of desirable products. In this context we require:

  • a change from traditional stoichiometric, high energy methods that produce huge amounts of chemical waste to mild and clean catalytic processes
  • a major step change in chemicals production with fossil fuels being replaced by renewable resources as chemical starter units.

The challenge to change our society’s reliance for chemical production from fossil-fuel based to all-renewable resources is of enormous scale. Lignocellulosic biomass is considered as one of best resources for the sustainable production of energy and chemicals. Lignin is the second most abundant bio-polymer after cellulose and the principle natural source of aromatic carbon. It is a three dimensional, amorphous polymer which consists of methoxylated phenylpropane units. These units are inter connected by different C-O and C-C linkages such as β-O-4, β-β, β-5. Our research focusses on the development of optimal catalysts for ether cleavage in 'real life samples' of lignin for maximising the potential of lignocellulose as a source of fuels and fine chemicals. Ruthenium catalysts based on wide bite-angle ligands have been explored for efficient ether bond cleavage, a crucial step in lignin degradation.

See also our publication list

C: ‘de novo’ design of transition metalloenzymes

The rates and selectivity of enzymatic catalysis are seldom equalled by transition metal catalysis. Still, many important fine chemicals are produced by homogeneous catalysis because efficient enzymes for important chemical transformations like CO- and alkene insertions are lacking. By combining the concepts of biology for selective recognition with those of transition metal catalysis we develop novel, highly selective catalysts for important (asymmetric) catalytic C-C bond forming reactions. Furthermore, high substrate specificity will allow conversion of a single substrate present in complex mixtures, like those in biological systems. Several approaches are being followed. We are working on advanced systems using transition metals that contain ligands based on rigid strongly coordinating phosphines modified with relatively small oligopeptide or oligonucleotide chains. The catalytic activity of these artificial metalloenzymes or “DNAzymes” stems mainly from the transition metal part, while the selectivity of the catalytic transformation is induced by molecular recognition between the peptide chain and functionalized substrates.
Use of proteins
The peptide chain can direct the orientation of the metal center and the substrates. By changing the length of the oligopeptide bridge and the amino acid sequence the catalyst structure can be optimized to obtain efficient and selective reactions. Studies are already in progress to couple organic ligand systems to enzymes like photoactive yellow protein (collaboration Hiemstra/Van Maarseveen and Hellingwerf, University of Amsterdam). We aim to improve the molecular weight distribution of the ethene oligomerisation products by creating steric congestion of the growing chain (collaboration van Leeuwen, University of Amsterdam). Therefore, we attach active nickel-phosphinophenol complexes covalently to enzymes containing an apolar cavity, such as photoactive yellow protein. Relatively simple nickel complexes can be attached to the cysteine (C-69) in the chromophore-binding pocket (see figure) The length of the product oligomers is expected to resemble the size of the hydrophobic cavities. Structural modification of the linker can influence the degree of steric congestion. In this way the average molecular weight and molecular weight dispersion can be optimised.

(A) shows a Ni-acetoacetate catalyst covalently linked to C69 with the surrounding amino acids; In (B) a growing heptyl chain is inserted into the empty chromophore-binding pocket of PYP; (C) shows the spatial structure of apo-PYP with the phosphinophenolate covalently attached, occupying a larger part of the cavity.

Use of nucleic acids
Phosphine-modified oligonucleotides can be used to create selective metal catalysts by forming secondary interactions between functionalised substrates and the nucleic acid bases. The advantage of using oligonucleotides is the well-defined secondary structure obtained by selective base pairing. Again, catalyst optimisation can be achieved both by modifying the oligonucleotide sequence and by adjusting the structure of the phosphine ligand part.

Computer model of PdCl2 complex of AGCTU*AGCT self complementary duplex; U* = 5-diphenylphosphinouracil

The catalytic activity of these artificial “DNAzymes” stems from the transition metal part, while the selectivity of the catalytic transformation is conferred by molecular recognition between the nucleotide chain and the substrates. Despite the fact that the secondary structure can be engineered simply by choosing the appropriate base sequence, folding and detailed effects on catalyst performance remain difficult to predict. Therefore, rapid catalyst modification and optimisation is required.

See also our publication list

D: Combinatorial development of transition metal catalyst libraries for cross-coupling reactions

The reactivity of organotransition metal complexes is dependent on the ligand environment of the metal. Consequently, optimizing the catalytic center by varying the ligand properties is a powerful tool in homogeneous catalysis. Impressive results have been obtained in both small-scale (asymmetric) catalytic preparation of fine-chemicals and industrial production of bulk-chemicals. While the increasing knowledge about organotransition-metal compounds and computational chemistry has provided fundamental knowledge of the factors influencing elementary reaction steps, catalyst development is still hampered by lack of insight in the transition state of the selectivity-determining step. Furthermore, in general a catalytic transformation consists of several elementary steps that will be influenced in different ways by ligand modifications. Therefore, rational design of ligands, in particular for enantioselective transformations, is far beyond reach and the development of efficient high-performance catalysts relies on ‘trial and error’. The latter is an incentive to develop a combinatorial approach, entailing a parallel ligand synthesis procedure together with rapid screening methods. Phosphines are still the most powerful ligands systems for industrial homogeneous catalysis. Yet, a combinatorial approach in homogeneous catalysis has not been applied to these highly successful phosphorus ligands because synthetic tools are lacking. Solid phase procedures are being developed to give access to a wide array of structurally diverse phosphine and phosphite ligands, which are applied in important catalytic reaction as enantioselective palladium catalyzed Heck reaction and allylic substitution and palladium catalyzed amination of aryl halides.

Modular approach for combinatorial ligand synthesis.

See also our publication list

In 2005 the universities of St Andrews and Edinburgh in Scotland together formed EaStCHEM: the Edinburgh and St Andrews Research School of Chemistry. Both EaStCHEM catalysis groups received grants from the main UK funding agency EPSRC to start a major effort in the field of renewable catalyis and to build links with the Dutch consortium CatchBio. The collaboration was suggested to Paul Kamer by Bob Tooze from Sasol, one of CatchBio’s consortium partners. Kamer also involved Nick Westwood and Andy Smith from St Andrews. “Our collaboration in EaStCHEM as well as with CatchBio should both be viewed in the same light: to join forces in an ambitious long term programme. No group, university or even country is large enough to face the gigantic challenges in the field of renewable feedstocks on its own. It is infinitely more complex than initially thought”, Kamer explains. “In my opinion, there is no alternative to a multi-faceted, integrated approach.”

Read more about this.....