Characterizing hydrogen bonds in crystalline form of guanidinium salicylate in the terahertz range

For pharmaceutical compounds with poor solubility, there is an effective method to address this dilemma without tampering their intrinsic chemical properties by forming weak hydrogen bonds. Guanidinium salicylate, which is a typical pharmaceutical salt with a complex crystal structure, was systematically investigated by terahertz time-domain spectroscopy combined with density functional theory in order to obtain the complete information of weak hydrogen bonds. As a result of the influence of weak hydrogen bonds, there are substantial differences between guanidinium salicylate and its parent molecule (salicylic acid) in the experimental fingerprint spectra in the range of 0.2–2.5 THz, such as the number, amplitude and frequency positions of absorption peaks. With the help of isolated molecule density functional theory calculations, the possible sites of weak hydrogen bonds were determined by natural bond orbital analysis. It can be concluded that there is an intricate hydrogen bond network due to the polar distribution of molecular electrostatic potential. Furthermore, all THz absorption peaks were assigned to their corresponding vibrational modes and the complete information of the related hydrogen bonds (including type, role, angle, and bond length) was determined by using dispersion-corrected density functional theory. The results laid a good foundation for further study on the enhancement of solubility of pharmaceutical salts by forming weak hydrogen bonds.