Research - Prebiotic Catalysis

Two contrasting models of prebiotic catalysis are being developed. The first is based on template catalysis in which the components of a dimer or higher oligomer bind specific monomers, the preorganisation of which aids bond formation to yield a complementary sequence (Figure 1).
This is the basis of DNA and RNA replication, but these highly evolved systems only replicate in the presence of external enzyme catalysts. Occasionally RNA can also act as a catalyst (a ribozyme) and the duel metabolic and informational role of this molecule has lead to the RNA world hypothesis. Although a number of synthetic systems are known that display the simple A-B replication sequence outlined in Figure 1, these are not applicable to the self-generation of longer sequences such as trimers, tetramers etc. Furthermore, all attempts to achieve the non-enzymatic replication of oligonucleotides using activated mononucleotides have proven unsuccessful. So is template catalysis a feasible mechanism for the replication of oligomer sequences? The attraction of this approach is that once a population of replicating molecules exists they become subject to Darwinian selection and may evolve in response to external stimuli. This in vitro adaptation of molecular populations has been termed unnatural selection, and although the technique has been demonstrated with DNA and RNA (with their associated enzyme catalysts), it has yet to demonstrated in any non-biological system that would correspond to a pre-biomimetic model of molecular population evolution.
Our approach to this problem is based on monomers A and B, pyridone substituted 1,1'-ferrocenes aligned for self-recognition (A-A and B-B = 4 hydrogen bonds) rather than A-B interaction (2 hydrogen bonds).
Further modification is envisioned to provide bifunctional C2-symmetric monomers for oligomer synthesis and replication studies (Figure 2).
The second approach to prebiotic catalysis involves generating populations of oligomers from two or more building blocks such as amino acids. The system is maintained far from equilibrium by the continual addition of both monomers and energy, the latter, for example, in the form of a peptide coupling reagent. In this state the system may display emergent behaviour manifested in observable features of the whole system (e.g. chirality amplification), due to the selective generation and operation of catalysts arising in the population. Compared to the methodology described above these experiments are more directly pre-biomimetic by there use of simple bifunctional monomeric building blocks of a type likely to have been present 4 billion years ago.