Mechanistic Analysis of Peptide Affinity to Single-Walled Carbon Nanotubes and Volatile Organic Compounds Using Chemiresistors

Peptides, due to their diverse and controllable properties, are used as both liquid and gas phase recognition elements for both biological and chemical targets. While it is well understood how binding of a peptide to a biomolecule can be converted into a sensing event, there is not the same mechanistic level of understanding with regard to how peptides modulate the selectivity of semiconductor/conductor-based gas sensors. Notably, a rational, mechanistic study has not yet been performed to correlate peptide properties to the sensor response for volatile organic compounds (VOCs) as a function of chemical properties. Here, we have designed a peptide that has (1) two amino acid residues that bind the sensor surface, (2) two flexible linkers (GG) that eliminate steric strain, and (3) a five amino-acid repeat that can bind the analyte of interest either by formation of a binding pocket (such as from peptides selected by phage display) or by forming a semiselective adsorption layer. The nine peptide sequences containing both a six amino acid constant sequence (WGGWGG) and a five amino acid variable sequence (XXXXX) were synthesized, and their impact on the selectivity and sensitivity of carbon nanotube (CNT) gas sensors was explored. The response of each sensor to the following VOCs with diverse chemical properties: isopropyl alcohol (polar protic), acetone (polar aprotic), isoprene (nonpolar, linear hydrocarbon), and toluene (nonpolar aromatic), was then recorded and analyzed. This study revealed multiple key factors that influence the response of peptides on CNTs to select VOCs. First, the stability of the CNT-peptide aqueous dispersion correlated to the aromaphilicity of the side chain, strongly suggesting that the side chains of peptides are interfacing with the CNT, and not the peptide backbone. Second, the sensing response profile cannot solely be explained by peptides adsorbing to the gas molecules with similar polarities/dielectrics and may instead be due to analyte displacement of the peptide side chain on the CNT surface as measured by changes in the peptide bond orientation using near-edge X-ray absorption fine structure spectroscopy (NEXAFS). These two observations create a new paradigm to explain how peptides confer selectivity to semiconductor-/conductor-based gas sensors and can provide insights into future design and implementation of peptide-coated solid state sensors for gas targets.