Competition between a replicator and an AB complex pathway in a dynamic scenario

After demonstrating that the dynamic combinatorial library can be influenced using the amplification engendered in the AB complex pathway and the self-replicating cycle. It is possible to envisage both these processes competing for staring material in a single system. The experiment is easily designed using the already utilised library, but this time using both the meta 179 and para 112 substituted maleimides together. Both maleimides compete for the recognition nitrone 177 formed in the exchange process. Since there are two maleimides present in solution a total of eight products can be formed: four cis isomers (cis-182, cis-184, cis-186, cis-188) and four trans isomers (trans-182, trans-184, trans-186, trans-188) (Figure 152). It is expected for two products to be amplified: trans-188 and cis-182.

N N H O N F N O F N N H O N O F N F N COOH O O N O O COOH

Figure 152. Addition of maleimides 179 and 112 to the dynamic combinatorial library created from imine 174 and nitrone 176 results in the formation of eight possible cycloadducts.

Basing our knowledge on previous experiments it is expected that the AB complex pathway will be faster than the self-replicator in the early stage of the reaction, therefore cis-182 product should be amplified more than trans-188.

When the imine-nitrone library is subjected to both maleimides 179 and 112 it is possible to distinguish all 13 fluorine-containing compounds in solution using

19

F NMR spectroscopy (Figure 153).

Figure 153. Distribution of compounds in a DCL generated from imine 174 and nitrone 176 together with maleimides 179 and 112 ([174] = [176] = [179] = [112] = 20 mM) after 16 h (-template, █). When the same experiment is repeated with 10 mol% of template

trans-188 the formation of trans-188 is enhanced (+ template, █). In both cases cis-182

is the dominating cycloadduct in the mixture.

cis-182 cis-184 cis-186 cis-188 trans-182 trans-184 trans-186 trans-188

174 176 173 177

112 179

In the product pool cis-182 is most abundant reaching a concentration of 8.5 mM and is 28 times higher than the next cis product. When comparing the trans cycloadducts it is apparent that the self-replicating trans-188 has the highest concentration and is the second most abundant product reaching 2.8 mM. The selectivity among the trans

isomers is not as good as among the cis series with the dominating trans-188 being only 3.3 times higher than the next trans product.

It is possible to make use of the templating properties of the replicator in order to enhance its performance. In the next experiment aside the two maleimides 179 and

112 10 mol% of preformed template trans-188 was added to the DCL. The hope was that such approach would even the chances in the competition for the hydroxylamine resource between the AB complex pathway and the replicator. An increase in the concentration of trans-188 at the expense of cis-182 was observed. The concentration of trans-188 replicator after 16 h reaches 4.3 mM, compared to 2.8 mM in the undoped reaction and the dominating cis-182 product reaches 7.5 mM which is 1 mM less then in the previous experiment. This experiment proves that the AB complex pathway being a more simple mechanism of utilising recognition as means of amplifying the rate of reaction dominates the replicator in a competition scenario. Since the recognition nitrone is being fed into the solution via the exchange the cycloaddition reactions have to perform at relatively low concentrations. This limitation favours the AB complex pathway, which is more efficient at lower concentrations than the replicator, which bases on the reactive ternary complex. The system and its emergent properties are another example of self-sorting. The amplification from a dynamic combinatorial library is performed in an ordered fashion through two distinct pathways. The compounds have engendered in their design the recognition-mediated reactivity and to what extent it can be utilised to promote their expression form the mixture.

4.8 Conclusions

The systems described here represent one of the first experimental notifications that combine the fundamental ideas behind the emerging area of systems chemistry in a small system. Firstly, the networks are based on dynamic combinatorial chemistry, but on top of that possess supramolecular recognition features, nonlinear amplification and self-replication. It is now possible to determine what are the minimal

requirements for such a system to operate. Utilising synthetically simple building blocks relying on a single recognition event to determine the fate of the system allows for a detailed kinetic study of how the systems evolve with time showing exquisite selectivity. Coupling of a thermodynamic process to a kinetic amplification technique is a promising approach to achieving high selectivity from a DCL. The significant response of the system to a small input of instructional template is also encouraging. This property suggests that it should be possible to develop more complex dynamic recognition-mediated reaction networks, relying on multiple recognition events, such as a combination of auto- and crosscatalytic replicators, to generate and express more complex programmed responses to template inputs through recognition- mediated processes. Systems chemistry attempts to capture the complexity and emergent phenomena prevalent in the life sciences within a wholly synthetic chemical framework. The unique coupling between thermodynamic and kinetic phenomena shown in a minimum complexity scenario brings us closer to understanding the workings of non-linear biological processes.

5. Dynamic reaction networks from simple