Expanding the range and versatility of ferrocene nucleic acids

Nucleic acids (such as DNA) are ubiquitous in nature since they hold the coding information through which all cells, proteins and other biological components of life are made and replicated. Nucleic acids are polymers or oligomers (small polymers), which means that they are made up of individual repeating chemical units (monomers) strung together in a line, rather like components in a mechanical chain.

Each component of DNA consists of a sugar and a phosphate unit (together forming the backbone), with the sugar attached to one of the four coding nucleobases A, C, G or T.

Ever since the structure of DNA was solved 60 years ago, chemists have been intrigued by the prospect of making structural alterations to examine how this might affect its function. For example, researchers have recently shown how artificial nucleic acids (where part or all of the backbone of DNA is replaced with non-biological components) can be used to template the formation of natural nucleic acids.

RPG TUCKER J IMG1 jpg

The structural relationship between DNA and a form of FcNA, where sugar units are replaced by ferrocene units along its backbone.

Our current work is focused on adding new functionality to nucleic acids. We are doing this by inserting a molecule called ferrocene into its backbone. Ferrocene is a redox-active compound not found in nature that contains an iron atom. It was first reported in 1951, two years before the structure of DNA was published. 

By incorporating ferrocene into a nucleic acid, instead of having a natural oligomer of repeating deoxyribose units as found in DNA (the D in DNA stands for deoxyribose, which is the sugar unit), we now have an artificial oligomer of repeating ferrocene units called FcNA or ferrocene nucleic acid.  So far, we have made and published one oligomer of FcNA, which consists of a series of ferrocenes strung together, with each linked to two thymine (T) nucleobases.  

The eventual use of these new metal-containing nucleic acids (for example, for electrochemical sensing applications) has yet to be established.  Our immediate challenge is to synthesise more of the molecular components in sufficient quantities, for example those with slightly different structures and with different nucleobases attached. Only by doing this can various forms of FcNA be made so that a full study of their behaviour and properties can be undertaken.

Prof James Tucker
University of Birmingham

 

Professor Tucker was awarded a Leverhulme Trust Research Project Grant in March 2013.