Molecular Motions

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 Molecular Motions

Fourier transform infrared spectroscopy analyzes most any sample with vibrations

Infrared light stirs vibrations in molecules, and how they shake reveals what they are. With a solid, liquid, or gas sample, Fourier transform infrared spectroscopy (FTIR) helps scientists investigate those molecular vibrations. “Every material has an infrared fingerprint—a combination of molecular vibrations that can be used to identify the sample,” says Michael Joerger, manager of the business unit on mid-infrared spectroscopy for research applications at Bruker Optics (Ettlingen, Germany).

FTIR exposes a sample to a wide frequency range of IR and records the spectrum of the vibrational energy created in the molecules. Joerger points out that Bruker’s best system covers far-IR to ultraviolet, which he calls “an extremely broad range.” By comparing the results to a database and using computational algorithms, scientists determine the makeup of the sample. The molecular vibration bands can typically be assigned to functional groups. “You can distinguish whether a band corresponds to a carbon–oxygen single or double bond, for example,” Joerger explains.

With attenuated total reflectance (ATR) accessories, the FTIR technique requires virtually no sample preparation. It can measure powders, liquids, pastes, and so on—using them just as they are. This is a very big benefit of FTIR.

At RTI Laboratories (Livonia, MI), director of materials sciences Lloyd Kaufman says, “We use FTIR for just about any unknown identification that comes in the door.” He adds, “Coupled with X-ray spectroscopy, we can get a clear picture of both the elemental and molecular chemistry associated with the sample.” Kaufman and his colleagues also use FTIR as a starting point for polymeric identifications.

Engineers and scientists use FTIR for disparate applications, from identifying unknowns in research and contaminants in quality control to characterizing additives in polymers and oxidation in failure analysis.

FTIR’s features

Some of the theory behind FTIR emerged in the early 1700s—particularly the Beer-Lambert law. This law explains why scientists can quantify molecules in a sample with FTIR, because the amount of IR that gets absorbed is proportional to the product of the sample’s thickness and the concentration of the molecule that absorbs the light. Using this, says Joerger, “you can nicely quantify components.”

This technology can also distinguish similar molecules. With pharmaceuticals, small molecular differences can make a big impact on safety and efficacy. So, FTIR can be used in the pharmaceutical quality control to ensure that a product includes the correct medicine, instead of a similar—and maybe less effective—one.

FTIR also delivers a range of other benefits. Beyond the longstanding theories involved in this technology, FTIR hit the commercial market close to 50 years ago. That makes the technique well-established, and it delivers reliability and reproducibility, plus many libraries exist for data analysis. As Joerger says, “More than one generation of scientists grew up using FTIR.”

Over the years, FTIR grew increasingly versatile, offering more modes. Scientists can combine FTIR with other technologies, such as microscopy, to add spatial information or Raman spectroscopy to have FTIR-Raman. By combining FTIR with circular dichroism, pharmaceutical scientists can distinguish between left- and right-handed versions of a chiral medicine. One report states: “Chiral properties play an important role in the determination of pharmacological actions of the drug.” 1 Many drugs are made up of both enantiomers, but some drugs have been replaced with singleenantiomer versions. Nonetheless, some investigators found that single-enantiomer versions did not outperform mixed versions, 2 but they noted that the mixed- and single-enantiomer versions were not compared directly in most cases.

FTIR can also be applied over time. Scientists in China used FTIR spectroscopy and IR microscopy to study traumatic axonal injury in rats.3 The results showed biomolecular changes in the corpus callosum—a structure that connects the left and right halves of the brain—at different time points after the injury. In fact, the scientists developed a computational algorithm that uses the data to predict the time since an injury. In another example of a temporal application, scientists from Georgia State University in Atlanta took FTIR measurements over time to study photosynthesis, particularly photosystem 1.4 They used this technique to examine specific states of biochemicals involved in converting sunlight to energy.

Although Joerger says that FTIR “couldn’t be much more versatile,” he adds that “significant technical improvements can still be made.”

Atmospheric adjustments

In the most sensitive applications of FTIR, the atmosphere can interfere with the signal. “In about 80% of mid-infrared FTIR applications,” says Joerger, “this is no issue, because we can go with an encapsulated system with desiccants inside or purge the system with dry air or nitrogen gas.”

But if a scientist takes FTIR to the edge, such as measuring molecular monolayers, atmospheric signatures can limit sensitivity. “In the far infrared, what nowadays many call terahertz, you run into the most intense atmospheric absorption,” Joerger explains. Here, purging a system makes it better, but not perfect by far. To completely overcome such limitations, researchers use an FTIR vacuum spectrometer with an entirely evacuated beam path, excluding atmospheric interferences by design.

To go to terahertz limits, scientists once turned to a bolometer, a device that requires cryogenic cooling, such as liquid helium, which can be expensive and unobtainable in some countries. Instead, researchers can now use a vacuum FTIR system, like Bruker’s VERTEX 80v with the new verTera option, which provides FTIR and continuous-wave terahertz spectroscopy in the same instrument. “This works without any cryogenic components,” Joerger says, “and it can reach a very low spectral range limit of 3 wavenumbers.” In discussing the potential applications of this technology, he mentions research on crystal structures, inorganic chemistry, polymorphism, polymers, high-resolution gas spectroscopy, and pharmaceutical research. “There’s probably much more,” he says, “because we are just starting to discover the exciting possibilities of this combination.”

Bruker’s VERTEX 80v with the verTera option provides FTIR and continuous-wave terahertz spectroscopy. (Image courtesy of Bruker Optics.)

Opportunities ahead

Despite FTIR’s long history, no one knows how far this technology can go. Engineers and scientists keep finding new ways to use it. Recently, Kaufman and his colleagues used FTIR, he says, “to characterize the cure profile of an adhesive system, by preparing exemplars cured at different temperatures including over-cured and decomposition temperatures, such that we could adequately assess an adhesive failure.”

As in many other areas of technology, scientists also expect easier-to-use options, such as Bruker’s Vertex FM, which combines far- and mid-IR, but uses the same optical components. “So, there is no risk of problems as you move between ranges,” Joerger explains.

The development of new platforms, new methods, more advanced data-analysis algorithms, and technology combinations keep this old technology new.


  1. Alkadi, H. and Jbeily, R. Role of chirality in drugs … an overview. Infect. Disord. Drug Targets2017 (epub ahead of print, doi: 10.2174/1871526517666170329123845.).
  2. Gellad, W.F.; Choi, P. et al. Assessing the chiral switch: approval and use of single-enantiomer drugs, 2001 to 2011. Am. J. Manag. Care2014, 20, 90–97.
  3. Zhang, J.; Huang, P. et al. Application of FTIR spectroscopy for traumatic axonal injury: a possible tool for estimating injury interval. Biosci. Rep.2017 (epub ahead of print, doi: 10.1042/BSR20170720).
  4. Makita, H.; Rohani, L. et al. Quinones in the A1 binding site in photosystem I studied using time-resolved FTIR difference spectroscopy. Biochim. Biophys. Acta.2017 (epub ahead of print, doi: 10.1016/j.bbabio.2017.06.006).

Mike May is a freelance writer and editor living in Texas. He can be reached at [email protected].