Learning from Proteins and Drugs: Receptors That Mimic Biomedically Important Binding Motifs - Designing Receptors for the Next Generation of Biosensors - page 37

Fig. 3 Some common carboxylic acid bioisosteres
Fig. 4 (a) Fluoride selective sensor developed by Starnes et al. (b) Cyanide selective receptor
developed by Ahn et al .
Fig. 5 Chloride selective fluorescent sensor developed by Johnson et al. ( left ) and its crystal
structure complexed with chloride ( right )
These groups have two possible modes of molecular recognition: when
protonated, the acidic hydrogen atoms should make excellent donors useful for
anion binding. When deprotonated, the anionic conjugate bases of these functional
groups are potential cation binders. Our group and others have investigated the use
of deprotonated tetrazolates for cation binding [ 38 - 43 ]. While aryl sulfonamides
have been used as anion binders, the affinities of tetrazoles and acyl sulfonamides in
neutral, protonated form have been largely unexplored.
Starnes and co-workers appended bis-aryl sulfonamide functionality to a well-
known porphyrin scaffold (3) and observed changes in the UV-vis absorption
spectra when titrating with various anions (Fig. 4a )[ 44 ], while Ahn et al . observed
fluorescence enhancement and selectivity towards cyanide with their naphthalene-
based aryl sulfonamide receptor (4) (Fig. 4b )[ 45 ]. Recently, Johnson and co-
workers have been developing aryl ethynyl scaffolds as anion sensors and have
shown remarkable fluorescence imaging of chloride in vitro [ 46 ]. They have also
fabricated a scaffold decorated with aryl sulfonamide functionality (5) that is also a
successful anion binder [ 47 ] (Fig. 5 ). Against this backdrop of favorable results, it is