Synthesis, crystal structure, hirshfeld surface analysis, spectral and quantum chemical studies of pharmaceutical cocrystals of a bronchodilator drug (Theophylline)

Abstract

Co-crystals of Theophylline Resorcinol monohydrate (THR) and Theophylline Pyrogallol monohydrate (THPY) have been crystallized and their molecular structures were determined by single crystal X-ray diffraction analysis. The molecular packing of THR is closely packed than THPY which influence the structure stability. The molecular geometry was optimized theoretically using Hartree-Fock (HF) and Density Functional Theory (DFT) methods. The OH-group in resorcinol is hydrogen bonded to theophylline forming a dimer ring R22(7) motif through NH···O and CH···O hydrogen bonding network which lies in the hydrophilic region. However, in THPY two bifurcated ring R21(6) and R21(5) motifs contribute greatly in constructing the crystal structure. The FT-IR and FT-Raman spectra of THR and THPY in crystalline state have been interpreted and the assignments agrees well with the calculated spectra. The solubility study is carried out to improve the pharmaceutical property of the drug. The assessment of intermolecular contacts and the interactions were quantified by Hirshfeld surface analysis and natural bonding orbital (NBO) analysis respectively. Besides, the Mulliken charge analysis and HOMO-LUMO analysis of the compounds were investigated by theoretical calculations. Antibacterial activity of THPY have shown good inhibition on pathogenic strains compared to its parent compound and therefore can be recommended to treat infections from Streptococcus pneumoniae.