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The complex interplay between systems and their environment plays an important role in processes ranging from self-assembly to evolution. Polymorphism, where, from the same ingredients different products can be formed, is likely to be an important enabler for evolutionary adaptation. Environmental pressures may induce polymorphic behaviour, where different pressures result in different structural organisation. Here we show that by combining covalent and non-covalent bond formation three distinct polymorphs can emerge from the same small dynamic molecular network: vesicular aggregates, self-replicating fibres and nanoribbons, depending on the nature of the solvent environment. Additionally, a particular set of conditions allows the transient co-existence of both vesicles and fibres.

The conditions that led to the formation of the first organisms and the ways that life originates from a lifeless chemical soup are poorly understood. The recent hypothesis of ''RNA-peptide coevolution'' suggests that the current close relationship between amino acids and nucleobases may well have extended to the origin of life. We now show how the interplay between these compound classes can give rise to new self-replicating molecules using a dynamic combinatorial approach. We report two strategies for the fabrication of chimeric amino acid/nucleobase self-replicating macrocycles capable of exponential growth. The first one relies on mixing nucleobase- and peptide-based building blocks, where the ligation of these two gives rise to highly specific chimeric ring structures. The second one starts from peptide nucleic acid (PNA) building blocks in which nucleobases are already linked to amino acids from the start. While previously reported nucleic acid-based self-replicating systems rely on pre-synthesis of (short) oligonucleotide sequences, self-replication in the present systems start from units containing only a single nucleobase. Self-replication is accompanied by self-assembly, spontaneously giving rise to an ordered one-dimensional arrangement of nucleobase nanostructures.

The work carried out in this thesis provides examples on how variations in building block design affect self-assembly and self-replication behavior in dynamic combinatorial libraries. Chapter 1 provides an introduction in which possible definitions of life are discussed, together with the main characteristics of living systems (like self-replication and metabolism) and an overview of recent developments on self-replicators based on peptides and nucleobases. In Chapter 2 we report two peptide-based self-replicators that were utilized to synthesize supramolecular polymers with controllable size and composition. Our observations indicated that the nature of the polymers was strongly affected by the morphology of the sheared seeds. In Chapter 3 we show how self-replication can be tuned by the length of the spacer in DCLs made from two structurally different building blocks. In Chapter 4 we discovered parasitic behavior between self-replicators formed from building blocks that differ by a single methylene unit. We observed that a 6-ring replicator can only emerge when assisted by a pre-existing 8-ring self-replicator. Aiming for diversification of self-replicators through a cross-catalytic pathway under out-from-equilibrium conditions, we used continuous flow-set-ups in Chapter 5. First, we set up a system with two building blocks and optimized the experimental conditions in terms of flow rate, time and starting replicator composition. We also report attempts to create a cross-catalytic cycle by introducing a third building block. Finally, in Chapter 6, our studies are placed in a broader perspective and future prospects are discussed.

We report dynamic combinatorial libraries made from a simple building block that is on the verge of enabling self-assembly driven self-replication. Adding a template provides a sufficient additional push yielding self-replication. Self-assembly and self-replication can emerge with building blocks that are considerably smaller than those reported thus far.

Self-replication plays a central role in the origin of life and in strategies to synthesize life de novo. Studies on self-replication have focused mostly on isolated systems, while the dynamics of systems containing multiple replicators have received comparatively little attention. Yet most evolutionary scenarios involve the interplay between different replicators. Here we report the emergence of parasitic behavior in a system containing self-replicators derived from two subtly different building blocks 1 and 2. Replicators from 2 form readily through cross-catalysis by pre-existing replicators made from 1. Once formed, the new replicators consume the original replicators to which they owe their existence. These results resemble parasitic and predatory behavior that is normally associated with living systems and show how such lifelike behavior has its roots in relatively simple systems of self-replicating molecules.