Semiconductor Superstructures with Multiple Synergistic Resonances for SERS Exploring Multiplex Noncovalent...

Noncovalent interactions (NCIs) are crucial for biological bond-forming events and have significant applications across various branches of chemistry. Here, we demonstrate for the first time the identification of multiple NCIs between two interacting species using semiconductor-based surface-enhanced Raman scattering (SERS) spectroscopy. This was accomplished by designing submicrometer-sized TiO₂ superstructures with synergistic effects of Mie and charge-transfer resonances for SERS enhancement, enabling the TiO₂/4-mercaptobenzoic acid (MBA) system to achieve both high SERS activity and interfacial charge-transfer sensitivity. The results clearly indicate that the vibrational frequencies of MBA shift in correlation with various intermolecular interactions from hydrogen-bonding to ionic interactions. Multiple SERS analyses of NCIs were conducted for both the four DNA bases and single-stranded DNA sequences. Additionally, we performed a proof-of-concept study utilizing the relative SERS intensity to detect the relative content of two bases in single-stranded DNA sequences. This study unlocks potential applications of semiconductor SERS for exploring intermolecular-specific interactions.