Catecholamines play important roles in biology but their structural similarity makes it challenging to construct synthetic receptors with selective binding. A combination of covalent and noncovalent binding groups in the hydrophobic core of water-soluble nanoparticles enabled them to recognize dopamine and epinephrine with an association constant (Ka) of 3-4 × 104 M -1 in water, an order of magnitude higher than previously reported. In addition, minute structural changes among analogues were detected including the addition or removal of a single hydroxyl or methyl group.