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

Molecular recognition is the key step in a wide range of controlled separat ion and chemical transformation processes, with enzymes performing this tas k 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 rec eptors able to recognize amino acids stereospecifically is attracting consi derable interest because therapeutic drugs, that may be developed from chir al amino acid intermediates, are increasingly required in enantiomerically pure form(1). Early work(2-4) has stimulated the development of efficient r eceptors based on small molecules(5-8), but binding of amino acids with hig h and predictable stereospecificity remains difficult to achieve. Directed molecular evolution(9), on the other hand, does select for RNA sequences or antibodies that bind amino acids with high specificity(10-12), but typical ly without providing insights into the molecular recognition mechanisms inv olved. Here we show that a rationally designed metal complex formed from a trivalent cobalt ion and a tetradentate ligand binds natural amino acids, i ncluding the simple yet challenging amino acid alanine, with high and predi ctable regio- and stereospecificity. We expect that our approach will allow the binding as well as separation and stereospecific catalytic formation o f its target amino acids.