Achieving Molecular Recognition of Structural Analogues in Surface-Enhanced Raman Spectroscopy: Inducing Charge and...

Area of Science:

• Analytical Chemistry
• Biochemistry
• Spectroscopy

Background:

• Surface-enhanced Raman scattering (SERS) faces challenges in recognizing complex isomeric biomolecules due to low sensitivity and specificity.
• Existing molecular probes offer sensitivity but lack spectral specificity for differentiating similar structures.

Purpose of the Study:

• To develop a SERS strategy for high spectral specificity in molecular recognition of structural analogues.
• To demonstrate effective differentiation of isomeric chondroitin sulfate (CS) using a charge and geometry complementarity approach.

Main Methods:

• Employed 4-mercaptopyridine (MPY) as a molecular probe for SERS analysis.
• Utilized chondroitin sulfate (CS) disaccharides with varying sulfation patterns as model analytes.
• Integrated experimental and in silico studies to investigate probe-analyte interactions.

Main Results:

• Achieved high spectral specificity through "charge and geometry complementarity" between MPY and CS isomers.
• Demonstrated site-specific, multidentate interactions mimicking molecular docking.
• Attained >97% classification accuracy for 4 CS isomers and identified potential interferences.
• Enabled multiplex CS quantification with <3% prediction error.

Conclusions:

• The "charge and geometry complementarity" strategy enables precise SERS differentiation of biologically relevant isomers.
• This approach significantly enhances SERS molecular recognition capabilities for complex biomolecules.
• The findings support practical SERS applications in biodiagnostics, food, and environmental surveillance.