Selection between Competing Self-Reproducing Lipids: Succession and Dynamic Activation

Abstract

Models of chemical evolution are central to advancing origins of life research. To design more lifelike systems, we must expand our understanding of molecular selection mechanisms. Here, we show two selection modes that produce evolving populations of self-reproducing species, formed through thiol-disulfide exchange. Competition between thiol precursors can give clear succession patterns based on steric factors, an intrinsic property. A separate, emergent selection mechanism-dynamic activating metathesis-was found when exploring competing disulfide precursors. These experiments reveal that additional species generated in the mixture open up alternative reaction pathways to form self-reproducing products. Thus, increased compositional complexity provides certain species with a unique competitive advantage at the expense of others.

Scheme 1. Selection of Metastable Self-Reproducing Surfactants

Formation and destruction steps cause population growth and decline for a kinetically stable replicator. New selection modes in a competing surfactant system generate succession patterns and competitive advantages through intrinsic structural factors (i) and dynamic activation (ii).

Scheme 2. Surfactant Precursors and Their Observed Relative Reactivity in the Studied Thiol–Disulfide Exchange

Three surfactant series with various headgroups (a, b, and c) and hydrophobic tail are accessible. The surfactant products are labelled analogously to the following example: 4ac = tail a + headgroup c. Two irreversible thiol–disulfide exchange reactions in turn form and then break down metastable species 4. 5 represents the generic corresponding dialkyl disulfide product formed from the parent thiol(s). Reactivity is proportional to the relative 4 formation and destruction rates from independent controls. Full kinetic data may be found in the SI.

Scheme 3. Competition between Sterically Differentiated Precursors Leads to Species Succession in Time

Destruction step with concomitant formation of product 5 omitted for clarity. n = 3; error bars (where visible) represent the standard deviation.

Scheme 4. Competition between Electronically Differentiated Precursors Leads to Surfactant Selection over Time by an Emergent Mechanism

Overlaid reactions of thiol 1a with precursor 2b alone (non-competition) and with a mixture of 2a and 2b (competition). Overlaid reactions of thiol 1a with precursor 2c alone (non-competition) and with a mixture of 2a and 2c (competition). Three-way competition experiment between thiol 1a and precursors 2a–2c. n = 3; error bars (where visible) represent the standard deviation.

Scheme 5. Reaction Pathways in a Competition Reaction: Fast Disulfide Metathesis Producing 2e Gives Access to an Efficient Route to 4ac

Scheme 6. Disulfide Consumption in a Competition Reaction between 2a and 2c for thiol 1a

[4aa] and [4ac] data may be found in Scheme 4b. n = 3; error bars (where visible) represent the standard deviation.

Scheme 7. Comparison of Synthetic Activation Strategies and Illustrative Energy Landscapes

Stepwise covalent activation, e.g., leaving group enhancement, relay ring-closing metathesis (RRCM). Traditional catalytic activation, e.g., Lewis acid catalysis, transition metal coordination. Dynamic covalent activation, e.g., disulfide metathesis. act = activating reagent, R = generic reagent, cat = catalyst, P = product.