Synthesis and characterization of a disulfide reporter molecule for enhancing pH measurements based on surface-enhanced raman scattering

In this paper, we describe the synthesis and characterization of 2,5-dimercaptobenzoic acid as a novel pH-sensitive disulfide reporter molecule for surface-enhanced Raman scattering (SERS) capable of inducing the controlled aggregation of gold (Au) colloids in solution without the addition of salts. While weak acids have been shown to yield some pH sensitivity as reporter molecules for SERS measurements, the reproducibility and signal strength of nanoparticle probes based on such molecules can vary greatly. This limited reproducibility depends greatly on the salt-induced aggregation of the colloidal nanoprobes, which is required in order to obtain SERS signals strong enough to probe individual clusters. This complicates their use in live cell sensing applications. We show that our approach results in primarily bridged nanoparticles comprising a pH-sensitive nanoprobe that can quantify accurately pH values well below 5.5. The robustness and sensitivity of this system makes it a powerful tool for measuring pH values on the nanoscale under in vitro conditions.