Controlled Aggregation of Citrate-Stabilized Gold Nanoparticles into Long-Lived Metastable Clusters

The controlled aggregation of plasmonic nanoparticles remains a critical challenge for achieving temporally stable and reproducible colloidal substrates for surface-enhanced Raman scattering (SERS). Here, we show that the antihistamine drug bilastine induces a concentration-dependent, self-limiting aggregation of citrate-capped gold nanoparticles (cit-AuNPs), producing long-lived metastable clusters in aqueous media. UV-Vis spectroscopy reveals the emergence and temporal evolution of a lower-energy, plasmon-coupling band, while dynamic light scattering (DLS) supports the formation of larger colloidal structures in suspension. Transmission electron microscopy (TEM) provides complementary qualitative evidence of concentration dependent changes in aggregate morphology. Zeta potential measurements show progressive interfacial charge regulation upon bilastine addition, consistent with perturbation of the citrate-stabilized interface. SERS spectra and citrate-control experiments support the presence of bilastine in the SERS-active interfacial region, with enhanced carboxylate-associated modes suggesting proximity of the carboxylate-containing region to the Au surface. Time-dependent optical measurements and semi-quantitative DLVO-type analysis indicate a slowly evolving, self-limiting aggregation regime at selected submicromolar bilastine concentration, whereas higher concentrations promote faster destabilization. The resulting aggregates retain SERS activity over extended periods, highlighting bilastine as a molecular modulator for generating long-lived SERS-active AuNP clusters.