Novel high-performance hybrid catalysts
Recently, combining the catalytic activity of transition metal complexes with the enantioselectivity of DNA produced impressive results. Hybrid catalysts produced from copper (Cu) (II) complexes and double-strand DNA demonstrated exceptional ability to catalyse a particularly challenging reaction in water with high enantioselectivity. This was the first such demonstration without conventional catalysts. The scientists behind that discovery launched the EU-funded project 'Asymmetric aza-Michael reactions catalyzed by hybrids metal-DNA' (AMMDNACAT) to develop new hybrid catalysts for asymmetric reactions in aqueous media. The focus was on the aza-Michael reaction, a reaction in synthetic organic chemistry that produces a range of biologically interesting products. Using green chemistry exploiting atom efficiency and eco-friendly solvents was an important consideration. Extensive research led to the serendipitous discovery of a new product catalysed by the Cu(II)–DNA system. Without the DNA, the catalyst gave rise to formation of the aza-Michael addition product. With the DNA, the system catalysed a different reaction (Friedel–Crafts alkylation) and a subsequent enantioselective protonation reaction with 52 % enantioselectivity. The result is the first known case of control over chemoselectivity due to the presence of DNA. It was also significant as an enantioselective protonation. These are quite challenging to achieve given small proton size, the inherent reversibility of the reaction and the requirement of kinetic control over protonation. Project results highlight the exceptional catalytic activity of this metal–DNA hybrid. Subsequent work focused on optimisation of the reaction conditions, investigation of other substrates and a mechanistic study to elucidate the role of DNA. The majority of reaction products can only be synthesised using the DNA technology. It enables production of many valuable organic molecules of potential use in manufacture of other biologically active molecules. Some kinetic studies within the project demonstrated acceleration of reaction rate greater than 600 times compared to the reaction catalysed only with Cu(II), the largest known effect with a non-enzymatic system. The mechanistic investigations revealed the crucial role of DNA. Further structural and functional investigations will pave the way to rational design of these hybrid catalytic systems for many other challenging yet important transformations.
Keywords
Hybrid catalysts, catalysis, synthetic chemistry, metal complexes, enantioselectivity, DNA, aza-Michael reactions, aqueous media, green chemistry, Cu(II), protonation, metal–DNA hybrid
