Origins of Life and Evolution of Biospheres

, Volume 41, Issue 5, pp 399–412

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

  • Paul J. Bracher
  • Phillip W. Snyder
  • Brooks R. Bohall
  • George M. Whitesides
Prebiotic Chemistry

Abstract

This article reports rate constants for thiol–thioester exchange (kex), and for acid-mediated (ka), base-mediated (kb), and pH-independent (kw) 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, ka = 1.5 × 10−5 M−1 s−1, kb = 1.6 × 10−1 M−1 s−1, and kw = 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 kex = 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, pKa 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.

Keywords

Thiol–thioester exchange Thioesters Origin of life Prebiotic chemistry Hydrolysis Dynamic covalent chemistry 

Supplementary material

11084_2011_9243_MOESM1_ESM.pdf (423 kb)
ESM 1Experimental procedure for the synthesis of thioester 3, experimental details of the kinetics experiments, representative plots for the analysis of kinetics data. (PDF 423 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Paul J. Bracher
    • 1
  • Phillip W. Snyder
    • 1
  • Brooks R. Bohall
    • 1
  • George M. Whitesides
    • 1
  1. 1.Department of Chemistry and Chemical BiologyHarvard UniversityCambridgeUSA

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