Functionalized Benzoxazole–Pyrimidine Derivatives for Deep Bioimaging: A DFT Study of Molecular Architecture and One- and Two-Photon Absorption

This study investigates how different substituents modulate the electronic structure and optical properties of seven derivatives of Pyrimidine-benzoxazole (FB.01) in DMSO, aiming to optimize their performance as deep bioimaging probes. The π-conjugated FB.01 core was functionalized with methyl, phenyl, N-oxide, exocyclic phenyl, carboxyl, N(OH)2, and pyridine. Geometry optimizations were performed using DFT (B3LYP/6-311+G(d,p) with SMD), followed by analysis of frontier orbitals, electronegativity, hardness, and total energy. TD-DFT and the Sum-Over-States approach simulated molar absorptivity spectra and two-photon absorption cross-sections. Results show that minor torsions influence optical responses: the FB.01 skeleton remains nearly planar, though substituents alter π-overlap and shift the LUMO, while the HOMO stays at −7.65 eV. N-oxide and carboxyl groups stabilize the LUMO, narrowing the energy gap (down to 5.20 eV in FB.04 and 6.07 eV in FB.06), whereas methyl widens it (6.38 eV). All compounds preserve a strong UV-band; conjugation increases absorptivity, and FB.04 exhibits a 31 nm red-shift. TPA grows with conjugation and peaks dramatically in FB.04 (23 GM), surpassing other derivatives. These findings highlight three design principles: strong acceptors like N-oxide effectively lower the LUMO and enhance TPA; additional aromatic rings boost one-photon absorption; and carboxyl or N(OH)2 groups finely tune polarity without disrupting planarity.