Stringent selection on kinetics of condensation reactions: early steps in chemical evolution

The emergence of chemical selectivity poses a central challenge in origins-of-life research. As demonstrated by analyses of asteroid and meteorite samples, abiotic chemistry is incredibly messy. Experiments show that even limited sets of reactive species can undergo vast numbers of distinct chemical transformations, leading to a combinatorial explosion of products. These explosions arise from the numerous ways in which reactants in mixtures can combine, generating large and chemically diverse ensembles that reduce or even preclude the possibility of productive pathways of chemical evolution. However, recent empirical studies have demonstrated that chemical systems can exhibit combinatorial compression - a marked reduction in product diversity relative to combinatorial expectations. This selection is observed under conditions of low water activity, such as in the dry phase of wet-dry cycling experiments. Here, we integrate transition-state theory with computer simulations to demonstrate that experimentally observed combinatorial compression is a consequence of kinetic selection in condensation-dehydration reactions. Kinetic selection depends on several key factors: (i) chemical connectivity, where multiple species can react with each other; (ii) at least one particularly reactive species - termed a "kinetic compressor"; and (iii) appropriate temperature, concentrations, and reaction times. We find that small differences in activation free energies, on the order of just ∼3 kcal mol-1, can dominate a kinetic landscape, dramatically limiting product distributions. Connected systems can favor a narrow subset of products, suggesting selection mechanisms in prebiotic contexts. Our results provide mechanistic insight into combinatorial compression, establish a quantitative framework for exploring the emergence of stringent chemical selectivity, and can guide future experimental efforts in chemical evolution.