IR vs Raman Spectroscopy

Raman and FTIR (Fourier-transform infrared) spectroscopy offer molecular information about the structure and composition of chemical and biological samples. Because of the fundamental principles that govern each technology, both can yield complementary information. However, frequently one technology is a better choice, depending on the nature of the application.

a. Raman spectroscopy yields information about intra- and intermolecular vibrations. The former provides a spectrum characteristic of the specific vibrations of atoms in a molecule and is valuable for identifying a substance, form, and molecular backbone configuration to name a few. The latter yields information about lower frequency modes, which reflect crystal lattice structure and polymorph form.

b. Infrared spectroscopy provides a “fingerprint region” of the spectrum where intramolecular vibrations are well-defined and highly characteristic of the bonding of atoms.

A practical example of differentiation between these two technologies is in the investigation of a crystallization process, in which Raman analyzes solid crystal form(s) and IR concurrently measures the solution-phase characteristics such as supersaturation.

Raman. The Raman effect is weak (often referred to as a one in ten million event), resulting from an energy event when photons of monochromatic light (laser) interact with a molecule that leads to a release of inelastic photons.

When photons interact with a molecule, an electron may be excited to a higher energy level (i.e. an excited virtual state) but not fully undergo an electronic transition. The electron then can relax to a vibrational energy level that is different than that of the incident energy. The difference between the energy of the incident photon and the energy of the scattered photon is called the Raman shift. The molecule's interaction with light can induce a shifting of the molecule's electron cloud that results in a change in polarizability. A molecule has specific energy transitions related to its intramolecular bonds in which a change of polarizability occurs, and these changes give rise to Raman active modes. The frequency of the Raman shift is related to the type of bond being excited and the intensity of this Raman peak is proportional to the number of those bonds.

IR. Infrared (IR) spectroscopy is a stronger technique that relies on the absorption of light by molecules at frequencies corresponding to the fundamental vibrations of those molecules. Molecules with functional groups that have strong dipoles display strong peaks in the IR, whereas functional groups that have weak dipoles and readily undergo a change in polarizability display strong peaks in Raman.

The motion of atoms in a molecule has a natural frequency of vibration related to their bond strength. When the frequency of a bond’s vibration is equal to the frequency of IR radiation directed onto it, the bond absorbs the radiation. The specific IR frequencies that a molecule's bonds absorb gives rise to an IR spectrum of the molecule.

Below we will outline the advantages and limitations of each technology along with reactions appropriate for each. Then we will explore how the instrumentation can provide value for key application areas and recent journal articles for further reading.

Raman and IR spectroscopy provides real-time profiling of reaction species and track reaction initiation, progress, transient intermediate(s), and end-point. They also allow rapid development of kinetics data and support proposed reaction mechanisms. Read more on synthesis reactions.

Both spectrometry methods can investigate catalytic bulk and surface structure, study adsorbed species on catalytic surfaces, examine ligand-metal bonding, develop structure-activity relationships and optimize catalytic processes by measuring the effect of reaction variables on product yield, quality, and catalyst activity. All of this can be done via in-situ IR and Raman spectroscopy under actual pressure/temperature, as well as analyzing homogeneous catalytic reactions in flow. Read more on catalytic reactions.

For a wide range of reaction classes, use inline chemically inert flow cells (Raman) and ATR flow cells (IR) to continuously monitor and ensure the stability of flow reactions. IR and Raman technologies support rapid process optimization studies in flow by tracking key reaction species as a function of varying flow conditions. Read more on continuous flow chemistry.

In-situ IR measures solutes in the solution phase for crystallization development, and in-situ Raman spectroscopy measures crystal growth and polymorphism as a function of variables such as solvents, seeding, cooling profile, temperature, and pH. Read more on crystallization.

In-situ IR and Raman analysis can be utilized to support various downstream processing steps including primary capture, buffer exchange, purification, bioconjugation, and formulation. In these applications and others, real-time analysis eliminates the traditional bottlenecks and delays associated with traditional offline, grab-sample analysis. Read more on downstream processing.

Raman spectroscopy is powerful for analyzing polymer backbone structure, chain length, ring opening, and conformation. Use IR spectroscopy for analyzing side chains, terminal end groups of long-chain molecules, and functional groups. Acquire data for reaction kinetics, monomer conversion rates, reactivity ratios, activation energies, the role of initiators, intermediates, and by-product formation all in real time without the need for extractive sampling and offline analyses. In-situ analysis eliminates the irreproducibility of offline sampling caused by increased reaction viscosity and missed analysis data points during fast polymerizations, thereby providing more accurate kinetic data. Read more on polymerization reactions.

The instrumentation and interface to the sample for these two techniques are similar in approach, but different in the details.

Raman spectrometers utilize a laser as the source (typically visible or near-IR laser), whereas IR spectrometers typically employ a black body radiator (such as a glow bar) to provide energy in the mid-infrared region.

Additionally, the optomechanical systems are different in that Raman spectrometers use a holographic grating with a highly sensitive CCD detector, and FTIR spectrometers use an interferometer to provide modulated radiation that is detected by pyroelectric (DTGS) or, more sensitive, photonic (MCT) detectors.

Both techniques use fiber optic probes for in-situ reaction monitoring. In the case of Raman, the fiber optic is composed of silica and can range in length from a few meters (2 m) to several (>50 m) meters or kilometers. IR fiber probes are constructed of a material that transmits mid-IR radiation such as chalcogenide glasses or silver halide (AgX) and is limited in length (<4 m) due to the natural attenuation of the IR energy by the fiber optic material. The interface between the sample and probe in FTIR spectroscopy is an internal reflecting ATR sensor made of diamond or silicon crystal, whereas the interface to the sample for in-situ Raman measurements uses a sapphire lens to focus the laser at a spot near the sapphire lens/sample interface.

ReactRaman™ and ReactIR™ are part of an integrated family of products that are combined across the iC Software™ platform to provide a co-understanding of reaction kinetics, mechanism, and pathway information for enhanced reaction characterization.

ReactRaman is an exceptionally compact, compact, interchangeable probe or flow cell-based Raman system that is optimized for in-situ monitoring of chemical reactions and crystallization processes. The system uses a 785 nm solid-state laser in order to reduce sample fluorescence while maintaining an excellent cross-section to maximize the Raman scattering signal. The laser energy is transmitted to and collected from the sample by fiber optic cables and a chemically hardened insertion probe equipped with a sapphire lens to interface with the sample. The scattered energy is passed onto a high-performance holographic grating, and finally, a CCD detector captures this energy to yield the Raman spectrum.

ReactIRis a compact FTIR spectrometer dedicated to chemical reaction monitoring with either an interchangeable insertion probe or flow cell that interfaces to batch or continuous flow syntheses, respectively. FTIR spectrometers, in general, consist of several key components – a light source (typically an infrared glow bar), an interferometer with both fixed and moving mirrors and a thermal or photonic detector. Broad band infrared energy from the source is directed onto a beamsplitter which passes the energy along two different paths. One path has a fixed mirror at the end, the other a moving mirror. The infrared energy from these two paths returns and recombines at the beam splitter causing a constructive and destructive interference pattern, the interferogram. This modulated infrared beam is passed to the sample where it is absorbed as a function of the molecular structure of the sample and therefore generates the IR spectrum for analysis.