Vibrational Spectroscopy

Vibrational spectroscopy probes the interaction of electromagnetic radiation with organic molecules by inducing higher energetic states in covalent bonds (vibrations). Thus, these techniques give information about the molecular structure of the sample, which is not easily achievable by other methods. The general use in solid-state characterisation is to provide a fingerprint, with which different crystal forms of the same molecule can be distinguished. Since the energy needed to excite a specific molecular group to vibration depends strongly on the chemical surrounding of this group, differences in the crystal packing will show a shift in certain absorption bands. For this reason, polymorphic forms can be normally distinguished by vibrational spectroscopy. Even more obvious is the difference between a non-solvated and a solvated crystal form, as the latter shows additional features of the incorporated solvent. With the modern techniques of Fourier transform infrared and Raman spectroscopy and the speed of data acquisition, vibrational spectroscopy presents an easy and valuable characterisation technique, which can be performed in every laboratory. Vibrational spectroscopy uses the somewhat archaic unit wavenumbers (cm-1), which is the inverse wavelength.

Infrared spectrometer in atenuated total reflection (ATR) mode

Infrared spectrometers are divided into several subclasses depending on the radiation they use. The most common instruments use mid-infrared radiation of 4000 to 400 cm-1 (2.5 to 25 μm wavelength). In this region, the fundamental molecular vibrations occur. These vibrations have to show a change in the dipole-moment of the vibrating group in order to absorb infrared radiation. Thus, mainly polar asymmetric groups are infrared active. Water for example is well detectable by infrared spectroscopy, and therefore hydrated crystal forms are perfect samples for this method. Depending on the interaction mode of the water with the host molecule mainly through hydrogen bonds, the O-H stretch band (approximately 3600 to 3300 cm-1) can be shifted from the upper end of its range (3600 cm-1, i.e. free water) to the lower end resulting in a shift of 300 cm-1. On the other hand, the hydrogen bond accepting group will similarly shift in its vibration. Obviously, identification of the water O-H stretch is difficult when the host molecule contain O-H groups or N-H groups, as their vibrations are in the same region and can overlap.

Less common but used especially in the pharmaceutical industry for water detection is infrared spectroscopy using the near infrared spectrum (12500 – 4000 cm-1). In this region of the spectrum, absorption overtones can be detected, and the technique offers a non-invasive probe for tablets in their blister packages or for in-process control.

The special technique of terahertz spectroscopy uses the infrared range corresponding to 130 to 3 cm-1. In this range, concerted vibrations of the whole molecule (lattice vibrations) can be detected. This technique, however, is mostly used for larger molecules such as DNA and proteins.

Complementary to infrared spectroscopy, Raman active vibrations change their polarisability when excited. Therefore, non-polar groups can normally be detected by Raman spectroscopy while polar groups show weak to no activity. Non-solvated polymorphs present the best samples for this technique, as even the slightest difference in the chemical surrounding can be detected in the vibration of the molecule. On the other hand, water cannot be detected by Raman spectroscopy and thus hydrates will show only very slight differences to non-hydrated crystal forms. The biggest advantage of this technique, however, is that glass is not Raman active, and it is thus possible to use this method as non-invasive probe without the necessity for sample preparation and disturbing the crystals.