Co-crystal/salt crystal structure disorder of trichloroacetic acid–N-methylurea complex with double system of homo- and heteronuclear O–H···O/N–H···O hydrogen bonds: X-ray investigation, ab initio and DFT studies

Abstract

The X-ray diffraction studies revealed disorder of a trichloroacetic acid-N-methylurea complex crystal structure, connected with a proton transfer via O-HÁÁÁO hydrogen bond. The observed structure corresponds to a co-existence of ionic (salt) and neutral (co-crystal) forms of the complex in the solid state in ratio 3:1, respectively. The geometrical analysis based on ab initio and density functional theory methods combined with the experimental research indicated that two different N-methylurea molecular conformations, defined by CNCN torsion angle, correspond to the neutral and the ionic form of the complex, respectively. The conformational changes seem to be connected with stabilization of the ionic structure after a proton transfer, as according to theoretical calculations this form of the complex (the ionic one) was unstable in the gas phase. A particular attention was focused on a system of a double intermolecular hydrogen bonds, O-HÁÁÁO and N-HÁÁÁO which join molecules into the title complex. The analysis of these interactions performed in terms of their geometry, energetic and topological electron density properties let for their classification into strong and medium strength hydrogen bonds. It was also found that the antibonding hydrogen bonding donor orbital occupation corresponded to the stabilization energy resulting from charge transfer in hydrogen bonds. Hence, it is postulated as a possible indicator of interaction strength.

Trimorphism of N-methylurea: crystal structures, phase transitions and thermodynamic stabilities

“…1 Many co-crystals and salts of NMU are reported in the literature. [2][3][4][5] Up to this study, the only known crystal structure of NMU is a stable form that was first proposed in 1933, 6 the structure was solved in 1976 by Huiszoon and Tiemessen 7 and lastly refined at 8 K by Chęcińska et al 8 NMU crystallizes in the orthorhombic system with the chiral (therefore non-centrosymmetric) space group P2 1 2 1 2 1 . Several studies investigated the enthalpies and entropies of fusion and solid-solid transition of urea, and its derivatives, including NMU where only the enthalpy of fusion of NMU has been reported.…”

Experimental and Theoretical Evidence for Supramolecular Self-Assembly and Hydrogen Bonding between Squaric Acid and 2, 6-Bis(2-benzimidazolyl)pyridine

“…However, the strength of the mutual interaction is very weak because of its long distance and the small positive charge, therefore, this kind of interaction can be ignored. It was reported that the topology of the electron density at BCP is an indicator of the strength of intermolecular interations 39 . The hydrogen bonds in C-F1 and C-F3 have relatively large electron densities (0.0924 -0.0922 a.u.…”

Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

“…However, in many instances, screening for cocrystals is preferable to screening for salts. For example, Salt formation is not possible when working with neutral molecules, as it requires at least one ionizable point on the API of interest [ 17 ]. Furthermore, screening for cocrystals is often preferable when working with weakly basic compounds due to the molecule’s pKa rendering it too low for the salt formation or forming a product with insufficient physical stability to provide an acceptable shelf-life [ 18 ].…”