A metal complex that binds α-amino acids with high and predictable stereospecificity

Abstract

Molecular recognition is the key step in a wide range of controlled separation and chemical transformation processes, with enzymes performing this task with an unsurpassed degree of selectivity. Enzymes contain only 20 simple amino acids, yet it remains difficult to rationalize or even predict these stereospecific recognition events. Nonetheless, the rational design of receptors able to recognize amino acids stereospecifically is attracting considerable interest because therapeutic drugs, that may be developed from chiral amino acid intermediates, are increasingly required in enantiomerically pure form1. Early work2,3,4 has stimulated the development of efficient receptors based on small molecules5,6,7,8, but binding of amino acids with high and predictable stereospecificity remains difficult to achieve. Directed molecular evolution9, on the other hand, does select for RNA sequences or antibodies that bind amino acids with high specificity10,11,12, but typically without providing insights into the molecular recognition mechanisms involved. Here we show that a rationally designed metal complex formed from a trivalent cobalt ion and a tetradentate ligand binds natural amino acids, including the simple yet challenging amino acid alanine, with high and predictable regio- and stereospecificity. We expect that our approach will allow the binding as well as separation and stereospecific catalytic formation of its target amino acids.