Synthetic routes for novel annulated chromeno[3,2:5,6]pyrido[2,3-d] imidazo[1,2-a]pyrimidines: Design, characterization, antimicrobial efficiency and theoretical studies

The novel annulated chromeno[3,2:5,6]pyrido[2,3-d]imidazo[1,2-a]pyrimidines 4–7 were efficiently synthesized from condensation reaction of the key precursor 3 with a variety of 1,2-bielectrophilic reagents namely 1,2-dichloroethane, oxalyl chloride, chloroacetic acid and chloroacetone. The antimicrobial activity of the prepared compounds in vitro against some microbial strains revealed significant efficiency especially compounds 5 and 7. Using analytical and spectral results, the structures of the synthesized products were established. DFT/B3LYP/6–311++G(d,p) basis set was used to compute HOMO and LUMO energies and global reactivity descriptors. Compound 1 has the largest HOMO–LUMO energy gap, whereas compound 5 has the smallest one. The Fukui functions (FFs) for the starting substrate 3 were calculated using the same level of theory to identify the more active sites during the chemical reactions. Molecular electrostatic potential (MEP) diagram displayed the susceptible locations for attack by electrophiles and nucleophiles. The B3LYP/6311++G(d,p) method was used to compute vibrational wavenumbers, and the results were compatible with the experimental data. Also, the ¹³C and ¹H NMR chemical shifts were estimated using the Gauge-independent atomic orbital (GIAO) approach and the results compared with the experimental data presenting excellent agreement. To explain the nonlinear optical (NLO) properties of the synthesized compounds, the dipole moment, polarizability, and first hyperpolarizability values were calculated and compared with urea as a reference material. ADME calculations were performed using the SwissADME method, which revealed that the present heterocyclic systems have safe physicochemical properties.