Thermodynamic control of asymmetric amplification in amino acid catalysis

Abstract

Ever since Pasteur noticed that tartrate crystals exist in two non-superimposable forms that are mirror images of one another--as are left and right hands--the phenomenon of chirality has intrigued scientists. On the molecular level, chirality often has a profound impact on recognition and interaction events and is thus important to biochemistry and pharmacology. In chemical synthesis, much effort has been directed towards developing asymmetric synthesis strategies that yield product molecules with a significant excess of either the left-handed or right-handed enantiomer. This is usually achieved by making use of chiral auxiliaries or catalysts that influence the course of a reaction, with the enantiomeric excess (ee) of the product linearly related to the ee of the auxiliary or catalyst used. In recent years, however, an increasing number of asymmetric reactions have been documented where this relationship is nonlinear, an effect that can lead to asymmetric amplification. Theoretical models have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally and rationalized mechanistically for an autocatalytic alkylation reaction. Here we show an alternative mechanism that gives rise to asymmetric amplification based on the equilibrium solid-liquid phase behaviour of amino acids in solution. This amplification mechanism is robust and can operate in aqueous systems, making it an appealing proposition for explaining one of the most tantalizing examples of asymmetric amplification-the development of high enantiomeric excess in biomolecules from a presumably racemic prebiotic world.

The Role of Stochastic Models in Interpreting the Origins of Biological Chirality

“…Finally, it should also be noted that claims for thermodynamic equilibrium as a driving force of symmetry breaking exist in the relevant literature [90,91]. It is necessary to further substantiate these claims based on a stochastic approach to thermodynamics.…”

Dynamic Processes in Prochiral Solvating Agents (pro-CSAs) Studied by NMR Spectroscopy

“…The populations of homo and hetero complexes are given in Equation (17). (17) where, [A] t is total concentration of chiral guest.…”

“…Examples of such potential uses are in in situ monitoring of various racemization, asymmetrical or enantioenrichment reactions, such as the Soai reaction [16] where the reaction outcome might be biased by addition of a standard chiral resolving agent (e.g., CSA) into the reaction mixture. Other examples involve drug racemization in the human body or rapid (in situ) analysis of experimental outcomes in studies regarding the origin of homochirality in nature [17][18][19]. Despite the limitation of the necessity for construction of a calibration curve, (which is inherent to pro-CSAs) it can lead to certain advantages (in specific tasks) over the classical ee discrimination methods.…”

Amino Acids in the Universe

“…Starting from such a small enantiomeric excess in the starting material, several physical processes allow to increase this ee on a sample. Sublimation [14], solubilization [15], crystallization [16] or distillation [17] are able to do it. This problem is discussed here with the sublimation.…”