The Relative Rates of Thiol-Thioester Exchange and Hydrolysis for Alkyl and Aryl Thioalkanoates in Water

Statistics – Applications

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Thiol-Thioester Exchange, Thioesters, Origin Of Life, Prebiotic Chemistry, Hydrolysis, Dynamic Covalent Chemistry

Scientific paper

This article reports rate constants for thiol-thioester exchange ( k ex), and for acid-mediated ( k a), base-mediated ( k b), and pH-independent ( k w) hydrolysis of S-methyl thioacetate and S-phenyl 5-dimethylamino-5-oxo-thiopentanoate—model alkyl and aryl thioalkanoates, respectively—in water. Reactions such as thiol-thioester exchange or aminolysis could have generated molecular complexity on early Earth, but for thioesters to have played important roles in the origin of life, constructive reactions would have needed to compete effectively with hydrolysis under prebiotic conditions. Knowledge of the kinetics of competition between exchange and hydrolysis is also useful in the optimization of systems where exchange is used in applications such as self-assembly or reversible binding. For the alkyl thioester S-methyl thioacetate, which has been synthesized in simulated prebiotic hydrothermal vents, k a = 1.5 × 10-5 M-1 s-1, k b = 1.6 × 10-1 M-1 s-1, and k w = 3.6 × 10-8 s-1. At pH 7 and 23°C, the half-life for hydrolysis is 155 days. The second-order rate constant for thiol-thioester exchange between S-methyl thioacetate and 2-sulfonatoethanethiolate is k ex = 1.7 M-1 s-1. At pH 7 and 23°C, with [R″S(H)] = 1 mM, the half-life of the exchange reaction is 38 h. These results confirm that conditions (pH, temperature, p K a of the thiol) exist where prebiotically relevant thioesters can survive hydrolysis in water for long periods of time and rates of thiol-thioester exchange exceed those of hydrolysis by several orders of magnitude.

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