Synthesis, X-ray Structure, Hirshfeld, DFT and Biological Studies on a Quinazolinone-Nitrate Complex

Area of Science:

• Inorganic Chemistry
• Crystallography
• Computational Chemistry
• Medicinal Chemistry

Background:

• 4-hydroxyquinazoline (4HQZ) is a heterocyclic compound with potential biological activities.
• Nitric acid reacts with 4HQZ to form a quinazolinone-nitrate (4HQZN) complex.
• Understanding the structural and electronic properties of 4HQZN is crucial for its applications.

Purpose of the Study:

• To synthesize and characterize the 4HQZN complex.
• To analyze the crystal structure, supramolecular assembly, and electronic properties of 4HQZN.
• To evaluate the biological activities (antioxidant, anticancer, antimicrobial) of both 4HQZ and 4HQZN.

Main Methods:

• Synthesis of 4HQZN via reaction of 4HQZ with nitric acid.
• X-ray crystallography for structural determination of 4HQZN.
• Density Functional Theory (DFT) calculations for isomer stability and medium effects.
• Biological screening assays for antioxidant, anticancer, and antimicrobial activities.

Main Results:

• 4HQZN was obtained in high yield and its crystal structure determined (monoclinic, P21/c).
• Supramolecular structure features 2D layers connected by N-H…O and C-H…O hydrogen bonds.
• DFT calculations indicated medium effects significantly impact isomer stability and structure.
• 4HQZN displayed higher antioxidant activity than 4HQZ; both showed anticancer activity against MCF-7 and A-549 cell lines, with 4HQZ being more potent.
• 4HQZN demonstrated superior antibacterial and antifungal activities, particularly against A. fumigatus.

Conclusions:

• The crystal structure of 4HQZN represents a proton transfer complex, with stability influenced by intermolecular interactions and solvent environment.
• 4HQZN exhibits promising enhanced antioxidant and antimicrobial properties compared to 4HQZ.
• While 4HQZ showed better anticancer activity, 4HQZN's antimicrobial potential warrants further investigation.