Solvates of New Arylpiperazine Salicylamide Derivative-a Multi-Technique Approach to the Description of 5 HTR Ligand Structure and Interactions

Edyta Pindelska, Anna Marczewska-Rak, Jolanta Jaśkowska, Izabela D. Madura
2021 International Journal of Molecular Sciences  
A new ligand for 5-HT1A and 5-HT7 receptors, an arylpiperazine salicylamide derivative with an inflexible spacer, is investigated to identify preferred fragments capable of creating essential intermolecular interactions in different solvates. To fully identify and characterize the obtained crystalline materials, various methods including powder and single-crystal X-ray diffraction, solid-state NMR, and thermal analysis were employed, supplemented by periodic ab initio calculations. The
more » ... tions. The molecular conformation in different solvates, types, and hierarchy of intermolecular interactions as well as the crystal packing were investigated to provide data for future research focused on studying protein–ligand interactions. Based on various methods of crystal structure analysis, including the interaction energy calculation and programs using an artificial neural network, a salicylamide fragment was found to be crucial for intermolecular contacts, mostly of dispersion and electrostatic character. A supramolecular 2D kite-type layer of {4,4} topology was found to form in crystals. The closed voids between layers contain disordered solvents, very weakly interacting with the molecule and the layer. It has been postulated that the separation of the layers might be influenced by an increase in temperature or the size of the solvent; hence, only methanol and ethanol hemi-solvates could be obtained from a series of various alcohols.
doi:10.3390/ijms22094992 pmid:34066719 fatcat:6mwf5fau3bgz3etfyhsxhsxaeq