Some high-affinity functional groups or resonant molecules were often used as probe molecules adsorbed on silver nanoparticles for Surface-enhanced Raman scattering (SERS). However, it is still unclear how the attached molecules interact with the silver nanoparticles' surface, and how the anchoring groups affect the optical and electronic properties of molecules. Here, we report that surface-enhanced Raman studies of two organic compounds; rhodamine 6G (R6G) and its aminated derivative (R-NH2) have very different functional groups for surface binding but nearly identical SERS spectroscopic properties at pH = 7 and UV–vis at pH = 3, respectively. A surprise was found that under the same experimental conditions, the SERS signal intensity for R6G is nearly 50-fold higher than that of R-NH2. Furthermore, the pH-dependent study reveals that the structure of R6G is irreversibly stabilized or ‘locked’ in its form and no longer responsive to pH changes. In contrast, R-NH2 is still sensitive to pH, and can be switched between its open-ring and closed-ring structures. Copyright © 2013 John Wiley & Sons, Ltd.