Low-frequency Raman spectroscopy

Significance of the Topic

Low-frequency Raman spectroscopy extends the accessible spectral range down to 65 cm-1, capturing low-energy vibrational and lattice modes that complement the fingerprint region. These unique spectral features enhance molecular identification and structural analysis in disciplines such as protein research, pharmaceutical polymorph screening, and materials science.

Objectives and Study Overview

The study aims to illustrate the capabilities of a portable Raman spectroscopy system for low-frequency measurements. Key goals include:

• Characterizing amino acid vibrational modes in the 65–3200 cm-1 range.
• Detecting and differentiating polymorphs and pseudo-polymorphs of active pharmaceutical ingredients.
• Monitoring phase transitions, exemplified by the α-to-λ transformation in sulfur.

Methodology

Measurements were performed at room temperature using a 785 nm excitation laser with power up to 300 mW. Integration times varied from 100 ms to 10 s, and spectral resolution was 4.5 cm-1. Data were averaged and processed with dedicated spectroscopy software to enhance signal-to-noise ratios.

Instrumental Setup

The analytical setup comprised:

• i-Raman® Plus 785S spectrometer with CleanLaze® technology, TE-cooled, back-thinned CCD detector.
• BAC102 E-grade fiber-optic probe providing a continuous measurement range from 65 to 33500 cm-1.
• Control and data acquisition via proprietary BWSpec software.

Key Results and Discussion

• Amino Acid Analysis: L-asparagine exhibited prominent low-frequency bands below 200 cm-1, critical for conformational studies.
• Polymorph Detection: The E-grade probe clearly distinguished α-D-glucose from its monohydrate form by unique peaks in the low-frequency region.
• Phase Monitoring: Thermal-induced melting of α-sulfur to its λ-form was tracked by peak broadening and shifting around 83.6 cm-1, with no significant changes in the fingerprint region.

Benefits and Practical Applications

Incorporating low-frequency Raman spectroscopy provides:

• Enhanced sensitivity and specificity in identifying molecular and crystal structures.
• Improved quality control for pharmaceutical manufacturing through reliable polymorph discrimination.
• Real-time monitoring of phase transitions in industrial processes.

Future Trends and Potential Applications

Expanding the technique to emerging fields may involve:

• In-depth analysis of semiconductor lattice dynamics.
• Characterization of carbon nanotubes and novel nanomaterials.
• Integration with multivariate analysis for automated process control.
• Portable, in-line monitoring solutions for solar cells, minerals, pigments, and gemstones.

Conclusion

The combination of the i-Raman Plus 785S and a low-frequency E-grade probe offers a cost-effective and versatile platform to probe molecular and lattice vibrations down to 65 cm-1. This approach facilitates advanced applications in biology, pharmaceuticals, and materials science, where subtle structural details are essential.

References

1. Teixeira AMR, Freire PTC, Moreno AJD, et al. High-Pressure Raman Study of L-Alanine Crystal. Solid State Commun. 2000;116(7):405–409. doi:10.1016/S0038-1098(00)00342-2.
2. Larkin PJ, Dabros M, Sarsfield B, et al. Polymorph Characterization of Active Pharmaceutical Ingredients (APIs) Using Low-Frequency Raman Spectroscopy. Appl Spectrosc. 2014;68(7):758–776. doi:10.1366/13-07329.
3. Golichenko BO, Naseka VM, Strelchuk VV, et al. Raman Study of L-Asparagine and L-Glutamine Molecules Adsorbed on Aluminum Films in a Wide Frequency Range. Semicond Phys Quantum Electron Optoelectron. 2017;20(3):297–304. doi:10.15407/spqeo20.03.297.
4. Smith E, Dent G. Modern Raman Spectroscopy: A Practical Approach. 2nd ed. John Wiley & Sons; 2019.
5. Pelletier MJ. Analytical Applications of Raman Spectroscopy. 1st ed. Blackwell Science; 1999.