Synthesis, crystal structure, electronic structure, and anti-tubercular properties of two new coumarin derivatives bearing theophylline moiety

In this work, synthesis, crystal and electronic structure of newly synthesized coumarin-theophylline hybrids exhibiting high anti-TB activity were investigated by experiments and quantum chemical calculations. The molecular structure determined by single crystal X-ray diffraction method revealed that the compound crystalize in the monoclinic system with the space group P2₁/c. The molecule is stabilized by strong and weak intra-/inter-molecular hydrogen bonds. The crystal structure compares well with the optimized geometry calculated at B3LYP/6–311++G(d,p) level by using density functional theory. The electronic structure of the compound has been explored by investigating frontier molecular orbitals, natural atomic charges, natural populations of the molecular orbitals, Hirshfeld and molecular electrostatic potential surfaces. It is realized that the compounds show substantial in vitro anti-tuberculosis activity with the MTBH₃₇Rv strain and were identified as a hit candidate, exhibiting MIC of 0.39 & 0.78 µg/mL against Mycobacterium tuberculosis.