One Hydrogen BondTwo Ways To Build a Structure. The Role of N–H···O Hydrogen Bonds in Crystal Structures of <i>N</i>,<i>N</i>‑Dimethylglycine

Crystal structures of amino acids are considered to mimic important interactions in peptides; therefore the studies of the structure-forming factors in these systems attract much attention. <i>N</i>,<i>N</i>-Dimethylglycine is an interesting model compound that was used to test the role of the N–H···O hydrogen bonds in forming the head-to-tail chains, the main structural unit in the crystals of amino acids. It was hypothesized previously [Kolesov, B. A.; Boldyreva, E. V. J. Raman Spectrosc. 2010, 41, 670−677] that additional side N–H···O hydrogen bonds play an important role in forming the head-to-tail chains of amino acid zwitterions linked via N–H···O hydrogen bonds between the charged −NH₃⁺ and −COO^– terminal groups. The twice methylated amino group of <i>N</i>,<i>N</i>-dimethylglycine is able to form only one N–H···O hydrogen bond in the crystal structure, so this hypothesis could be tested. In the present article, we describe the crystal structures of two polymorphs of <i>N</i>,<i>N</i>-dimethylglycine, in which the zwitterions are packed in two different ways. In one polymorph (orthorhombic, <i>Pbca</i>), they form finite four-membered ring motifs not linked to each other via any hydrogen bonds but only by weak van der Waals interactions. However, in the second polymorph (monoclinic, <i>P</i>2₁/<i>n</i>, which was never described before), the zwitterions do form infinite head-to-tail chains though the N–H···O bond is the only interaction and is not assisted via any additional hydrogen bonds. The effect of cooling on the two crystal structures was followed by single-crystal X-ray diffraction combined with polarized Raman spectroscopy of oriented single crystals, in order to compare the response of the N–H···O bonds to temperature variations. The crystal structure of the monoclinic polymorph with infinite chain motifs compresses anisotropically on cooling, whereas that of the orthorhombic polymorph with finite ring motifs undergoes a reversible single-crystal to single-crystal phase transition at ∼200 K accompanied by nonmerohedral twinning, reducing the space symmetry to monoclinic (<i>P</i>2₁/<i>b</i>) and doubling the asymmetric unit from two to four molecules. This phase transition could not be detected by Raman spectroscopy and DSC. The temperature dependent structure and relative stability of both polymorphs were studied by periodic DFT calculations. The monoclinic polymorph appears to be more stable (by 0.8–1.2 kcal/mol, depending on the density), but with the increasing density and decreasing temperature, the difference decreases. The phase transition of the orthorhombic polymorph has no detectable impact on its relative stability