The experimental and theoretical landscape of a new antiplatelet drug ticagrelor: Insight into supramolecular architecture directed by C-H ••• F, π ••• π and C-H ••• π interactions

The crystal and molecular structure landscape of a new drug ticagrelor has been investigated by using experimental and theoretical approach. The structures of this cyclopentyl-triazolo-pyrimidine derivative, (1) and its DMSO solvate (2), were determined by SC-XRD at 100 K. (1) crystallizes in the orthorhombic space group P2(1)2(1)2 with four independent molecules, while (2) belongs to the monoclinic system with the space group C2, including two ticagrelor and 0.5 DMSO molecules in the asymmetric unit. Both crystals present diverse interactions, such as: O-H center dot center dot center dot O, N-H center dot center dot center dot O and C-H center dot center dot center dot X (X = O, N, F, S). H-bonds between N-triazolopyrimidine and -OH groups of cyclopentane-1,2-diol ring connect ticagrelor molecules into dimers forming three fused rings, encoded as R-2(2)(9) and R-2(2)(10) graph-set motifs, which are further linked by C-hydroxyethoxy-H center dot center dot center dot F-C-3,C-4difluorophenyl into a supramolecular chain. A comparative insight into the studies of all contacts in the crystal lattices of ticagrelors and other related adenosine derivatives from the CSD was provided using Hirshfeld surface analysis. It highlights a significant difference in terms of various substituents. Notably, F center dot center dot center dot H/H center dot center dot center dot F are more meaningful than O center dot center dot center dot H/H center dot center dot center dot O and N center dot center dot center dot H/H center dot center dot center dot N H-bonds. The pi center dot center dot center dot pi stacking and C-H center dot center dot center dot pi interactions participate in a cooperative way to stabilize the supramolecular architecture. The geometry of both ticagrelor forms was optimized in the gas-phase and solvated state, using the DFT method, at the Becke 3LYP/B97D level. The theoretical results show a good agreement with those obtained from the X-ray study. Moreover, structural elucidation of a new drug was extended by 1D H-1, C-13 NMR, 2D H-1, C-13 HSQC NMR, FT-IR and TG/DTG techniques. (C) 2017 Elsevier B.V. All rights reserved.