RESUMEN
3-Hydroxybenzaldehyde (3-HBA) was investigated in the range of 0.6-2.8 THz by terahertz time-domain spectroscopy (THz-TDS) and solid-state density functional theory (ss-DFT) with first-principles calculation. Four distinct peaks were found respectively, and among them, the intensity disparity between experiment and simulation spectra at 2.04 THz was recognized as the biggest inconsistency. Considering thermal behavior can be responsible for this, quasi-harmonic approximation (QHA) method was introduced to mimic the unit cell volume expansion. According to vibrational modes analysis, it was ascertained that the biggest vibrational modes discrepancy was also located at 2.04 THz. Molecules in 0% and 4% unit cell expansion exhibit an opposite rotational direction in a-b plane compared with 2% unit cell expansion. Noncovalent intermolecular interactions were investigated with independent gradient model (IGM), and the result indicates that hydrogen bonding is the dominating noncovalent interaction of 3-HBA. While calculating systematic potential energy to the displaced bonds stretching involving hydrogen atoms, it was found the anomalous potential energy variation to the bond stretching provides a possible explanation for the rotation direction divergence, that is, the rotation direction divergence can be related to some hydrogen atoms seeking lower overall potential energy around their equilibrium positions during bond stretching in response to the variational intermolecular van der Waals force. This research combined THz-TDS with the quasi-harmonic approximation method, elucidating the principle of vibrational characteristics in different volumes, which is beneficial to the investigation of the terahertz low-frequency vibration to thermal behavior as a reference in biochemistry and other fields.
RESUMEN
While theophylline has been extensively studied with multiple polymorphs discovered, there is still currently no conclusive structure for the metastable theophylline form III. In this present work, by combining more widely used techniques such as X-ray diffraction and thermogravimetric analysis with more emerging techniques like low-frequency Raman and terahertz time-domain spectroscopy, to analyze the structure and dynamics of a crystalline system, it was possible to provide further evidence that the form III structure has a theophylline monohydrate structure with the water molecules removed. Solid-state density functional theory simulations were paramount in proving that this proposed structure is correct and explain how vibrational modes within the crystal structures feature and govern polymorphic transitions and the metastable form III. Through the insight provided by both simulated and experimental results, it was possible to decisively conclude the elusive crystal structure of theophylline form III. It was also shown that the correct space group for theophylline monohydrate is not P21/n but, in fact, Pc.