Dynamic Covalent Capture: A sensitive tool for detecting molecular interactions

Molecular recognition is at the centre of many areas of chemistry. Examples are analytical chemistry (analyte-sensor), catalysis (transition state-catalyst), medicinal chemistry (drug-biotarget) and advanced materials chemistry (building block A-building block B). Methodology that allows the rapid and precise detection of molecular recognition events is essential in all these fields. Traditionally, molecular recognition has been studied based on a rational design approach involving many iterative optimisation loops, which makes it an energy- and time consuming process. Additionally, it requires detailed knowledge about the target and the recognition process itself, information which is not always available. Currently, combinatorial methods are increasingly being used for detecting molecular recognition events, allowing the simultaneous screening of a vast amount of chemical compounds enabling a much larger part of chemical space to be explored. Dynamic covalent capture extends on the combinatorial approach for detecting molecular recognition events, but at a higher sensitivity level compared to conventional methodologies and with the novelty of self-selection by the target. The essential point of dynamic covalent capture is that a molecular recognition event is followed by the formation of a reversible covalent bond between the two molecules