Probing noncovalent interactions in biomolecular crystals with terahertz spectroscopy.

The far-infrared vibrational spectra of molecular crystals are dominated by intramolecular (internal) modes, which are also present in the isolated molecule, and noncovalent intermolecular modes, which arise from the interaction of the nearest neighbours (external modes). Conceptually this has long been understood and early experiments using Fourier transform infrared (FTIR) spectroscopy confirmed the existence of a rich vibrational spectrum in polypeptides in the low-energy region. Yet, the assignment of the experimentally observed peaks in the low-energy region is often unsatisfying. Recently, the advent of terahertz time-domain spectroscopy (THz TDS) has revitalized the field. Using this convenient room-temperature technique, noncovalent interactions between several smalland medium-sized molecules have been investigated, including nucleobases and nucleosides, short-chain polypeptides, cystine and glutathione, retinal, and saccharides. Chen et al. and Nagai et al. could clearly distinguish between intramolecular and intermolecular modes by comparing crystalline structures and solvated molecules. Furthermore, it was shown that different isomers as well as diverse crystalline forms show distinctively different terahertz spectra. Most of these experiments have benefited from a comparison with quantum-mechanical calculations of the normal modes, which are nowadays feasible due to advances both in computer technology and software development. Herein, we study two types of molecular crystals—one with weak [dimethyluracil (DMU), see Figure 1] and one with strong hydrogen bonds [thymine (THY), see Figure 2]. In order to gain insight into the chemical nature of the THz signals by assigning individual low-frequency modes, we compare our data to a