How left-handed amino acids got ahead

A demonstration of the evolution of biological homochirality in the lab

A chemical reaction that demonstrates how key molecules in the biological world might have come to be predominately left or right handed has been reported by scientists at Imperial College London.

Ever since discovering that the building blocks of the biological world, such as amino acids and sugars, are distinctively left or right handed – possessing a quality known as chirality – scientists have been puzzling to answer how and why.

They believe that at the dawn of biological life there were even numbers of molecules in each form, but through hitherto unknown processes, one particular form came to completely dominate over the others (for example left-handed amino acids and right-handed sugars), a feature known as homochirality.

Now, using simple organic molecules, the Imperial researchers have demonstrated that an amino acid itself can amplify the concentration of one particular chiral form of reaction product. Importantly, the experiment works in similar conditions to those expected around pre-biotic life and displays all the signs to suggest it may be a model for how biological homochirality evolved.

The research is published this week in the journal Angewandte Chemie International Edition.

Today, chemists regularly make catalysts that will steer a reaction towards products in one particular left or right form. Known as asymmetric reactions, they are commonly used in the pharmaceutical industry to make drugs which are active in the body in only one of the chiral forms.

“Chemists today can make templates to steer towards one form or another, but what happened at the beginning of the world when no such templates existed?” asks Professor Donna Blackmond, Professor of Catalysis at Imperial and senior author on the paper.

Over 50 years ago, a theorist explained how domination of one chiral form may arise. F.C. Frank suggested in 1953 that a tiny amount of one particular chiral form may become amplified into an excess over the other, through a process known as autocatalysis ñ where the substance acts as a catalyst for producing more of itself. His paper concluded with the teasing words: “A laboratory demonstration may not be impossible.”

Until 1995, researchers searched in vain to conquer what had been further dubbed ‘a challenge to all red-blooded chemists’. That year Kenso Soai and colleagues from Tokyo University demonstrated the first reaction to meet the Frank criteria, using an organozinc compound as catalyst.

In 2003, Professor Blackmond first heard reports by chemists at the Scripps Research Institute of a new reaction catalysed by proline, an amino acid.

What caught her eye was that the reaction appeared to be much faster than other proline-catalysed reactions.

Back in her laboratories she began to run the reaction, analysing it with sensitive calorimetry equipment that continuously monitors its rate. Proline indeed catalysed the reaction, exhibiting an unexpectedly high, accelerating reaction rate and an amplification of product excess in one particular chiral form; both tell-tale signs of a reaction that can rationalize the evolution of biological homochirality.

“This work may offer the first purely organic complement to the Soai reaction in the search for the chemical origin of life,” says Professor Blackmond.

The research was supported by EPSRC/DTI/LINK and Mitsubishi Pharma. Parts of the experimental work were carried out in the Department of Chemistry, University of Hull, where Professor Blackmond previously worked.

Notes to Editors:

Title: Amplification of Enantiomeric Excess in a

Proline-Mediated Reaction

Journal: Angewandte Chemie International Edition Vol 43, Issue 25 (June 21, 2004)

Authors: Suju P. Mathew, Hiroshi Iwamura* and Donna G. Blackmond

Department of Chemistry, Imperial College, London SW7 2AZ United Kingdom

* Permanent address: Mitsubishi Pharma Corporation, 14 Sunayama, Hasaki-machi, Ibaraki 314-0255, Japan.

Professor Donna Blackmond ñ biographical notes

Professor Blackmond, a US citizen, holds the College’s Chair in Catalysis, a joint appointment between the Departments of Chemistry and Chemical Engineering at Imperial.

She joined Imperial in January 2004, from the University of Hull, having previously worked at the Max Planck Institute in Germany, Merck and Co, and the University of Pittsburgh.

Professor Blackmond receives significant research funding from AstraZeneca, for whom she also regularly consults.

Home page: http://www.ce.ic.ac.uk/common-room/people/dgb.htm

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