Label-Free SERS Discrimination of Purine Small-Molecule Biomarkers: DFT Insight into Interfacial Binding Mechanism

Area of Science:

• Computational Chemistry
• Spectroscopy
• Biomarker Detection

Background:

• Uric acid (UA) and xanthine (Xa) are structurally similar small molecules with potential roles as biomarkers.
• Surface-enhanced Raman scattering (SERS) is a sensitive technique for molecular detection.
• Understanding molecule-substrate interactions is crucial for optimizing SERS-based sensing.

Purpose of the Study:

• To investigate the interaction mechanisms between UA/Xa and Au-enhanced substrates using DFT.
• To explore the theoretical feasibility of a label-free SERS detection strategy for UA and Xa.
• To elucidate the physical principles governing SERS enhancement for these molecules.

Main Methods:

• Density functional theory (DFT) calculations were employed.
• Molecular electrostatic potential (ESP), binding energies, frontier molecular orbitals (FMOs), and charge density differences (CDDs) were computed.
• Theoretical Raman/SERS spectra of UA/Xa-Au6 complexes were analyzed.

Main Results:

• DFT calculations identified potential active sites (carbonyl groups, N7 nitrogen) for UA/Xa-Au interactions.
• Stable molecule-metal complexes were confirmed through binding energy calculations.
• Charge-transfer excitations and selective spectral enhancements were observed, varying with docking configuration.

Conclusions:

• A label-free, sensitive, and high-throughput SERS detection strategy for UA and Xa is theoretically feasible.
• The study deepens the understanding of molecule-substrate interactions in SERS.
• This work provides a promising approach for detecting structurally similar small-molecule biomarkers.