Discovery of Linear Receptors for Multiple Dihydrogen Phosphate Ions Using Dynamic Combinatorial Chemistry

• Published in: Journal of the American Chemical Society Vol. 133; no. 11; pp. 3804 - 3807
• Main Authors: Beeren, Sophie R, Sanders, Jeremy K. M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 23-03-2011
• Subjects: Chromatography, High Pressure Liquid; Circular Dichroism; Combinatorial Chemistry Techniques; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Phosphoric Acids - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja200130h

We describe the use of dynamic combinatorial chemistry to discover a new series of linear hydrazone-based receptors that bind multiple dihydrogen phosphate ions. Through the use of a template-driven, selection-based approach to receptor synthesis, dynamic combinatorial chemistry allows for the identification of unexpected host structures and binding motifs. Notably, we observed the unprecedented selection of these linear receptors in preference to competing macrocyclic hosts. Furthermore, linear receptors containing up to nine building blocks and three different building blocks were amplified in the dynamic combinatorial library. The receptors were formed using a dihydrazide building block based on an amino acid-disubstituted ferrocene scaffold. A detailed study of the linear pentamer revealed that it forms a helical ditopic receptor that employs four acylhydrazone hydrogen-bond donor motifs to cooperatively bind two dihydrogen phosphate ions.