Innovative Green Synthesis and Multifunctional Applications of Pyrimidopyrimidine Derivatives

Introduction: This research introduces an eco-friendly, one-pot multicomponent synthesis of pyrimidopyrimidines (4a-4i) and amino-1,3-dimethylpyrimidines (5a-5d) in an aqueous medium, utilizing citric acid as a catalyst. Aims: The study aimed to establish a sustainable method for synthesizing these heterocyclic compounds while evaluating their biological activities. Methods: Structural characterization of the synthesized compounds was conducted through elemental analysis, IR, and NMR spectroscopy. The DPPH, TAC, and ABTS methods as-sessed the antioxidant properties, revealing their significant potential as bioactive agents. Compound 4i demonstrated the highest antioxidant activity with a DPPH inhibition of 99.13%, while compound 5b exhibited the highest ABTS activity of 100%. Advanced com-putational analysis using Density Functional Theory (DFT) at the B3LYP/6-311+G(d,p) lev-el provided insights into the compounds' molecular structures, reactivity, and electronic properties. Results: Key findings include the energy band gap analysis, which revealed compound 4c as the most stable (energy gap 5.102 eV) and compound 4i as the most reactive (energy gap 3.51 eV). These theoretical calculations, aligned with experimental NMR data, validated the molecular structures and confirmed the accuracy of theoretical predictions. Additionally, an-tibacterial and antifungal assays identified compound 4i as the most effective against Gram-positive and Gram-negative bacteria and Candida albicans. Conclusion: This work highlights the potential of these derivatives as promising candidates for therapeutic applications and contributes to advancing environmentally benign synthetic methodologies.