Insight into structural description of novel 1,4-Diacetyl-3,6-bis(phenylmethyl)-2,5-piperazinedione: synthesis, NMR, IR, Raman, X-ray, Hirshfeld surface, DFT and docking on breast cancer resistance protein

Abstract In this work, novel 1,4-diacetyl-3,6-bis(phenylmethyl)-2,5-piperazinedione (2) is prepared exclusively as the (R,S)-stereoisomer evidenced and confirmed by X-ray diffraction analysis. In addition, spectroscopic (NMR, IR, Raman) analyses were used to characterize the new compound. 2 crystallizes in the Pbca orthorhombic space group, with a symmetry center located at the centroid of the diketopiperazine ring. The structure of 2 is compact with the two phenyl rings folded over and under the diketopiperazine ring, conferring thereby a unique S shape to the molecule. The crystal structure is stabilized by intramolecular interactions, whereas the crystal packing is stabilized by intermolecular H-bond and C−H···π interactions. The different intermolecular interactions were confirmed using Hirshfeld surface analysis and molecular fingerprint. Molecular 2D fingerprint that quantify the different interactions highlights that H···H (58.2%), H···O/O···H (24.8%) and C···H/H···C (14.2%) account for 97.2% of all contacts. The topology of the interaction energy in the crystal structure is obtained and described. The Cremer and Pople puckering parameters indicate that the diketopiperazine ring adopts a flattened chair conformation with Θ = 0.00 ° and Q = 0.2233 (11) A. Moreover, a computational investigation revealed that the optimized structure of 2 using DFT calculation shows excellent agreement with the experimental data. As potential pharmacological active molecule, the molecular docking on breast cancer resistance protein (BCRP) reveals that 2 could interacts with the binding domain residues Phe728, Tyr949, Ser975 and Val978 and could be consider as promising BCRP inhibitor.