Reaction dynamics: OH electron, where art thou?

253 news & views reactions. Furthermore, it was found that AB-functionalized building blocks were prone to intramolecular cyclization on the DNA template, whereas much better intermolecular coupling efficiences were achieved by using mixtures of AA-and BB-modified building blocks. A range of coupling chemistries were explored, including amine acylation, reductive amination, hydrazine formation and oxime formation. In some of these cases the coupling efficiency was found to be quite poor, and when the reactions did work, there were concerns regarding the stability of the resulting daughter polymers. Eventually, it was found that the Cu(i)-catalysed alkyne– azide 1,3-dipolar cycloaddition reaction gave excellent yields of the desired (and stable) translation products. The concept of using well-established copper(i)-mediated click chemistry for the coupling of building blocks through an AA/BB strategy is not in itself new 5. Previous work has demonstrated the applicability of this reaction for efficient polymer synthesis, but only now — through its combination with a DNA template — can its true potential be demonstrated through the introduction of sequence control. Impressively, the coupling of 16 consecutive substrates is demonstrated, to afford a synthetic polymer containing 90 β-amino acid residues in a specific sequence. A key feature of this approach is that the resultant polymers (Fig. 1b) have no structural relationship with the nucleic acid template and hence the elegance of this artificial translation system is its ready applicability to any building block that is compatible with the coupling chemistries used. The question remains, however, whether this strategy will be used more widely? Although the idea is elegant and the concept ideally suited to the formation of sequence-controlled polymers, it is unlike the majority of controlled polymer-synthesis strategies pursued so far. Previous successes towards sequence-controlled polymers have typically utilized well-established polymerization methods that can be controlled by modulating the reaction kinetics or chain-end reactivity 6,7. The approach reported by Liu and co-workers is very different; it genuinely is a synthetic-biology approach to polymer synthesis. It draws inspiration from the ribosome with its use of codon/ anticodon recognition (although redesigned with five-base-pair instructions) combined with simple condensation chemistries for the polymer synthesis (yet using macrocyclic substrates for entropic considerations). The idea seems so simple, but its real beauty is in the ability to read out the initial code that made the sequence-controlled material — thus providing polymer synthesis methods with a route for selection and even perhaps non-biological materials evolution. This feature opens …