Electron‐Donating Benzenethiols Direct Rapid Formation of Plasmonic Gold Nanoflowers

ABSTRACT Gold nanostructures with branched morphologies exhibit strong plasmonic properties, enabling advanced biosensing and biochemical applications. Here, we report a rapid and scalable synthesis of gold nanoflowers (AuNFs) using modified benzenethiols as both reducing and capping agents. Benzenethiols bearing electron‐donating substituents promoted rapid Au 3+ reduction and anisotropic branch growth, completing particle formation in less than 10 s without seed preparation or organic‐aqueous transfer steps. The resulting AuNFs had abundant plasmonic hot spots and intrinsic Raman reporters, serving as dual‐modality probes for colorimetry and surface‐enhanced Raman scattering (SERS). When integrated into lateral flow assays, AuNFs markedly enhanced analytical sensitivity. In oxycodone detection, limits of detection reached 4.48 pg/mL (colorimetry) and 0.38 fg/mL (SERS), representing 700‐fold and 1,200‐fold improvements, respectively, over spherical gold nanoparticles. This performance enabled accurate quantification of oxycodone in plasma samples from murine addiction models. The developed method provides a practical route for preparing high‐performance plasmonic nanomaterials for applications in biosensing, catalysis, and analytical chemistry.