Synthesis, crystals structures, DFT, and anticancer activities of polycyclic heterocyclic quinones

• Four crystal structures of polycyclic heterocyclic quinone are obtained. • "Hydrogen atom substitution" (HAS) method is the first method proposed to divide total weak interaction. • HAS method is successful if the substituted group has no strong electronic effect. • The energies of many weak interactions are calculated in this study. In this work, we synthesized six polycyclic heterocyclic quinones (PHQs) and one unexpected product (compound 6 ). We verified all of their structures by 1 HNMR, 13 CNMR, and HRMS and obtained four crystal structures of the seven products. At first, we compared the crystal structures with crystal structures similar to those reported in the literature and explained their differences by conjugative effect, hyperconjugative effect, and electrostatic effect. Then, we compared the crystal structure of compound 6 with the calculated structure of compound 6 . The natural bond orbital analysis showed that the calculated structure formed intramolecular hydrogen bonds, whereas the crystal structure formed intermolecular hydrogen bonds but not intramolecular hydrogen bonds. The main reason for this difference was not due to the atomic charge or the interatomic distance, but rather the energy levels of the orbitals of the lone-pair electrons. In crystal structures, the intermolecular interactions contained many weak interactions, and we used the hydrogen atom substitution (HAS) method to divide the total intermolecular interactions as several independent weak interactions and to calculate their energies. The HAS method was often successful if the substituted group did not have a strong effect on the electronic structure of the entire molecule, and we found examples in the calculations of energies of weak interactions of crystal structure of compound 6 and compound 3a . An unsuccessful example of the HAS method was the substitution of C = O group with CH 2 group to eliminate the O … H-N hydrogen bond interaction from the total interaction. According to the HAS method, our calculations showed that the strength order of the weak interactions was as follows: π-π stacking > hydrogen bond > n -π stacking > σ-π stacking. For the hydrogen bond, the strength order was as follows: C = O … H-N > C Cl … H-N > C-F … H-N. For n- π stacking interaction, the strength order was as follows: Cl-π > N -π > F -π. Finally, we selected five synthesized PHQs to test anticancer activities and some of them showed better anticancer activities than the positive control drugs.