This dissertation will focus on detecting analytes in aqueous solution that chemically react with or bind to functional groups near the opening of synthetic ion channels derived from gramicidin A (gA). Detection is achieved when a measurable change in the conductance of ions across the ion channel is produced after the analyte interacts with the channel. Ion channel sensors have great potential for achieving ultrasensitive detection since a single chemical modification near the lumen of the channel can lead to detectable changes in channel conductance. The dissertation will specifically focus on: (1) the development of design parameters to improve sensing with gA-based nanosensors; (2) the demonstration of sensing analytes in aqueous solution by manipulating the charge of a chemical group near the pore of gA (charge-based sensing); (3) the chemistry for producing reactive building blocks of gA for developing robust and diverse gA -based nanosensors; (4) the detection of enzyme activity using our charge-based sensing approach to achieve picomolar limits of detection; and (5) the small structural changes that can be introduced to the peptide near the lumen of the channel to control conductance

Understanding molecular recognition is of fundamental importance in applications such as therapeutics, chemical catalysis and sensor design. The most common recognition motifs involve biological macromolecules such as antibodies and aptamers. The key to biorecognition consists of a unique three-dimensional structure formed by a folded and constrained bioheteropolymer that creates a binding pocket, or an interface, able to recognize a specific molecule. Here, we show that synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specific molecules. To prove the generality of this phenomenon, we report three examples of heteropolymer-nanotube recognition complexes for riboflavin, L-thyroxine and oestradiol. In each case, the recognition was predicted using a two-dimensional thermodynamic model of surface interactions in which the dissociation constants can be tuned by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatiotemporal sensors based on modulation of the carbon nanotube photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages.