Capture and Detection of Fentanyl with Thiolated Cucurbit[7]uril Macrocycles on Silver Nanoparticles

Opioid availability and use has expanded in recent years, leading to a dramatic increase in overdose-related deaths and presenting occupational hazards resulting from exposure to fentanyl and related agents. The high potency of fentanyl is especially concerning given it is often added to other illicit drugs of abuse in poorly defined quantities; its presence may furthermore be unknown to the user or other individuals encountering the drug substance. Supramolecular macrocycles from the cucurbit[n]uril family are known to bind fentanyl and related agents. Here, the selectivity of CB[7] to bind fentanyl in solution is demonstrated by competitive NMR studies with 1 mol% fentanyl in complex drug mixtures of either cocaine or diphenhydramine, which are common cutting agents. A thiolated version of the CB[7] macrocycle is also synthesized for the first time, thereby enabling direct attachment of CB[7] to the surface of silver nanoparticles (AgNPs). The ability to modify nanoscale colloids with CB[7] has direct application as capture agents in conjunction with the use of AgNPs for surface-enhanced Raman spectroscopy (SERS). When compared to unmodified CB[7], the thiolated CB[7] offers a significant enhancement in fentanyl detection using AgNPs and SERS, with a limit-of-detection of 0.37 nM. Despite these improvements, non-specific binding of the fentanyl to the AgNPs surface remains, limiting the specificity and selectivity of fentanyl capture in conjunction with SERS detection. However, the binding selectivity of CB[7] towards fentanyl suggests it could be leveraged in the design of nanomaterial sensor platforms for the measurement of fentanyl and related compounds in complex mixtures of illicit drugs.