Importance of R-CH3•••O tetrel bonding and vinyl•••aryl stacking interactions in stabilizing the crystal packing of 2’,4’-dihydroxy-3’-methoxychalcone: exploration of antileishmanial activity and molecular docking studies

• A new dihydroxymethylchalcone was isolated from Argentinean type-Zuccagnia propolis. • The crystal structure was solved by single crystal X-ray diffraction. • A detailed analysis of the main non-covalent interactions has been performed by using Hirshfeld surface analysis. • The intermolecular contacts were also studied by DFT calculations. A detailed experimental and theoretical investigation of a chalcone derivative 2’,4’-dihydroxy-3’-methoxychalcone ( DHMC ) isolated from Argentinean type-Zuccagnia propolis has been performed. The isolated compound was characterized by 1 H and 13 C Nuclear Magnetic Resonance (NMR), infrared (IR) and Raman spectroscopies and its crystal structure was solved by single-crystal X-ray diffraction (XRD). The molecular geometry of the title compound was investigated theoretically and a very good agreement between experimental and computed geometrical parameters and vibrational frequencies have been observed. The substance crystallized in the orthorhombic P bcn crystal system, with Z= 8 molecules per unit cell. The molecular geometry of the molecule is mainly stabilized by intramolecular O-H•••O(keto) hydrogen bonds. The structure reveals that the crystal packing is mainly governed by O-H•••O and C-H•••O hydrogen bonds. The supramolecular assembly of the compound in solid state is also stabilized by σ-hole tetrel bonding interactions (O•••C) involving the O-atom of the hydroxyl and the carbon atom of the methoxy group. Other interactions such as C-H•••π and vinyl•••π stacking interactions are also relevant in the stabilization of the solid structure of DHMC . The interaction energies of the different self-assembled dimers have been estimated using DFT calculations and various computational tools including MEP surfaces, QTAIM, NBO and NCI plot analysis. The antileishmanial activity of DHMC indicates that the compound was active against the main specie that cause tegumentary leishmaniosis in Argentina. The computational molecular docking simulation was used to predict the binding potential of the title chalcone derivative against six different leishmanial protein targets. The CH 3 •••O tetrel binding and vinyl•••aryl stacking interactions in the crystal structure of 2’,4’-dihydroxy-3’-methoxychalcone have been investigated using X-ray crystallography and DFT calculations.