Applications of Raman Spectroscopy

Identification of functional groups in unknown substances in solids and aqueous solutions. 

Identification of reaction components—Reaction kinetics study. 

Surface studies using Surfaee enhanced Raman spectroscopy (SERS). 

Quantitative and qualitative analyses of inorganic and organic compounds can be performed by Raman spectroscopy. Raman spectroscopy is used for bulk material characterization, online process analysis, remote sensing, microscopic analysis, and chemical 

Quantitative analysis had not been as common as in IR spectroscopy until recently, due to the high cost of Raman instruments. With prices for Raman systems dropping below 40,000, and even as low as 10,000, the use of Raman spectroscopy for quantitative analysis is increasing. Quantitative analysis requires measurement of the intensity of the Raman peaks and the use of a calibration curve to establish the concentration-intensity relationship. The intensity of a Raman peak is directly proportional to the concentration  

and v are all constants for a given sample measurement. The frequency and intensity of the desired Raman lines are measured, and the intensity of an unknown compared to the cahbration curve. It is common to use an internal standard for Raman analysis, because of the dependence of the signal on the laser power (in the K term). Without an internal standard, the laser power, sample alignment, and other experimental parameters must be carefully controlled. If an internal standard is used, the intensity of the internal standard peak is also measured, and the ratio of intensities plotted vs. concentration. Upon division, this reduces Eq. (4.14) to  

Another use of Raman spectroscopy for quantitative analysis is the determination of percent crystallinity in polymers. Both the frequency and intensity of peaks can shift on going from the amorphous to the semicrystalline state for polymers. The percent crystallinity can be calculated with the help of chemometrics software. 

Qualitative analysis by Raman spectroscopy is very complementary to IR spectroscopy and in some cases has an advantage over IR spectroscopy. The Raman spectrum is more sensitive to the organic framework or backbone of a molecule than to the functional groups, in contrast to the IR spectrum. IR correlation tables are useful for Raman spectra, because the Raman shift in wavenumbers is equal to the IR absorption in wave-numbers for the same vibration. Raman spectral libraries are available from commercial and government sources, as noted in the bibliography. These are not as extensive as those available for IR, but are growing rapidly. 

K is the proportionality constant including instrnment parameters such as laser power J is the scattering constant for the given Raman peak V is the scattering freqnency of the Raman peak c is the concentration of analyte 

Raman spectra of common drugs of abuse, showing how sharp the Raman spectral lines are. ( Thermo Fisher Scientific (www.thermofisher.com). Used with permission.) 

The use of the internal standard minimizes the effect of changes in instrnmental parameters and can result in better accuracy and precision. Newer Raman systems snch as the Thermo Scientific DXR series incorporate a laser power regulator that delivers reproducible laser power to the sample and compensates for laser aging and variability, minimizing the need for internal standards. 

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Myers A B and Mathies R A 1987 Resonance Raman intensities A probe of excited-state structure and dynamics Biological Applications of Raman Spectroscopy yo 2, ed T G Spiro (New York Wiley-Interscience) pp 1-58... 

Figure Bl.2.11. Biologically active centre in myoglobin or one of the subunits of haemoglobin. The bound CO molecule as well as the proximal and distal histidines are shown m addition to the protohaeme unit. From Rousseau D L and Friedman J M 1988 Biological Applications of Raman Spectroscopy vol 3, ed T G Spiro (New York Wiley). Reprinted by pennission of John Wiley and Sons Inc.

There are tluee very important sources of up-to-date infonnation on all aspects of Raman spectroscopy. Although papers dealing with Raman spectroscopy have appeared and will continue to appear in nearly every major chemical physics-physical chemistry based serial. The Journal of Raman Spectroscopy [35] is solely devoted to all aspects, both theoretical and experimental, of Raman spectroscopy. It originated in 1973 and continues to be a constant source of mfonuation on modem applications of Raman spectroscopy. 

D. A. Long. Raman Spectroscopy. McGraw-Hill, New York, 1977. A standard reference work on Raman spectroscopy with much theoretical detail on the underlying physics. Most of the needed equations for any application of Raman spectroscopy can be found in this book. 

Until today the only available data obtained by direct sampling of a prototype battery system concerning mass flow of the complexing agents as well as the Br2 produced in both the aqueous and non-aqueous electrolyte phases have been gained by application of Raman spectroscopy [89, 90]. 

Before discussing specific examples of the application of Raman spectroscopy to studying adsorbate-adsorbent interactions, it will be necessary, at this juncture, to explain the nature of the Raman effect. 

Raman spectra (for both the solid state and aqueous solution) provide better fingerprints for heparins than their i.r. spectra.79 However, the application of Raman spectroscopy to glycosaminoglycans is less routine than with i.r., both for instrumental reasons and because of possible interference from traces of fluorescent impurities.77... 

N.J. Everall, Industrial applications of Raman spectroscopy. In D.L. Andrews and A.A. Demidov (Eds.), An Introduction to Laser Spectroscopy, Plenum Press, New York, 1995, pp. 115-131. 

N. Everall, Chapter 4, Raman spectroscopy of synthetic polymers. In M.J. Pelletier (Ed.), Analytical Applications of Raman Spectroscopy, Blackwell Science, Oxford, 1999, pp. 127-192. 

Fortunately, in favorable cases enhancement mechanisms operate which increase the signal from the interface by a factor of 105 — 106, so that spectra of good quality can be observed - hence the name surface-enhanced Raman spectroscopy (SERS). However, these mechanisms seem to operate only on metals with broad free-electron-like bands, in particular on the sp metals copper, silver and gold. Furthermore, the electrodes must be roughened on a microscopic scale. These conditions severely limit the applicability of Raman spectroscopy to electrochemical interfaces. Nevertheless, SERS is a fascinating phenomenon, and though not universally applicable, it can yield valuable information on many interesting systems, and its usefulness is expected to increase as instrumentation and preparation techniques improve. 

Raman spectroscopy is emerging as a powerful analytical tool in the pharmaceutical industry, both in PAT and in qualitative and quantitative analyses of pharmaceuticals. Reviews of analyses of pharmaceuticals by Raman spectroscopy have been published.158 159 Applications include identification of raw materials, quantification of APIs in different formulations, polymorphic screening, and support of chemical development process scale-up. Recently published applications of Raman spectroscopy in high-throughput pharmaceutical analyses include determination of APIs in pharmaceutical liquids,160,161 suspensions,162 163 ointments,164 gel and patch formulations,165 and tablets and capsules.166-172... 

These and many other examples discussed in a review by Mestl and Srinivasan [47] show that Raman spectroscopy is indispensable in investigating the preparation of molybdenum catalysts. Several other applications of Raman spectroscopy in catalysis are discussed in a book by Stencel [48]. 

Further details of the theory and application of Raman spectroscopy in polymer studies can be found elsewhere (1. 9). However, vibrational frequencies of functional groups in polymers can be characterized from the spacing of the Raman lines and thus information complementary to IR absorption spectroscopy can be obtained. In addition, since visible radiation is used the technique can be applied to aqueous media in contrast to IR spectroscopy, allowing studies of synthetic polyelectrolytes and biopolymers to be undertaken. Conformation and crystallinity of polymers have also been shown to influence the Raman spectra Q.) while the possibility of studying scattering from small sample volumes in the focussed laser beam (-100 pm diameter) can provide information on localized changes in chemical structure. 

More examples of forensic applications of Raman spectroscopy have been published recently. It has been used to identify individual crystals of drugs and excipients on paper currency [110], multilayer paint chips, inks, plastics [111], and fibers [112], A study demonstrated the feasibility of quantifying acetaminophen in the presence of many excipient types [113], Other studies seek to identify particulates, such as illicit or abused drugs, in fingerprints lifted at a crime scene [114,115]. 

W.E. Smith, Surla.ceenha.ncedresonanceRmn n scattering, in Pharmaceutical Applications of Raman Spectroscopy, S. Sasic (Ed), Technology for the Pharmaceutical Industry Series, John Wiley Sons, Ltd, Hoboken, 2008. 

D.S. Hausman, R.T. Cambron and A. Sakr, Application of Raman spectroscopy for on-line monitoring of low dose blend nniformity, Int. J. Pharm., 298, 80-90 (2005). 

A. Kudelski, Analytical applications of Raman spectroscopy, Talanta, 76, 1-8 (2008). 

Spiro, T. G. Biological Applications of Raman Spectroscopy Wiley New York, 1987 Vol. 3. 

Significant progress has been achieved in the identification of poly sulfides in non-aqueous solvents, mainly by application of Raman spectroscopy. However, there are... 

Graselli, J. G., Snavely, M. K., Bulkin, B. J. Chemical Application of Raman Spectroscopy, New York—Chichester—Brisbane—Toronto, John Wiley Sons, Inc. 1981... 

T. G. Spiro Biological Applications of Raman Spectroscopy Resonance Raman Spectra of Heme and Metalloproteins, (1988) Wiley, New York. 

The slow-scan CCD, also called the scientific CCD, or in the spectroscopy literature simply CCD, is the detector of choice for most applications of Raman spectroscopy. A well-designed CCD has essentially zero dark current, very low readout noise, and high quantum efficiency (peak 45—70% near 700 nm) in the visible region of the spectrum. However, the response drops quickly above 800 nm and there is no photon response above 1.05 J m. For routine spectroscopy or process control, thermoelectrically cooled (to about —40° C) CCDs are adequate. Although these detectors are somewhat noisier than detectors operated at —100° C or lower, the former do not require liquid nitrogen cooling. The general properties and spectroscopic applications of the CCD have been reviewed (22). 

The application of Raman spectroscopy becomes more challenging when samples exhibit significant fluorescence (e.g., sediment samples which are brown in color). Other difficulties occur when hydrate samples contain occluded gas (e.g., the vC-H peak for methane gas overlaps with that for methane in the small cage of structure I hydrate). In this case, care must be given to assignment of the spectra (Hester, 2007). The latter example illustrates the strength of combining Raman and NMR spectroscopy to ensure correct interpretation of the data. 

Raman spectroscopy is a complementary technique that yields the same vibrational information as is obtained in conventional IR absorption spectroscopy. Here, however, the exciting radiation is in the visible region of the spectrum. Application of this technique to surfaces has been difficult because of practical problems associated with fluorescence. This problem now has been essentially resolved, and recent progress in the application of Raman spectroscopy to surfaces is reviewed by Morrow. 

In a different application of Raman spectroscopy to studies of zeolites, Cooney and Tsai (6) have investigated the adsorption of bromine on alkali exchanged zeolites X, NaY and NaA, and the... 

M. Pelletier, Analytical Applications of Raman Spectroscopy (Blackwell, Oxford,... 

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