Integrated theoretical and experimental analysis of 4-amino-N-methylphthalimide: structural, spectroscopic, and...

The structure of 4-Amino-N-methylphthalimide (4AMP) was investigated through spectroscopic techniques and quantum chemical calculations. Structural parameters were optimized using the DFT-B3LYP/6-311++G(d,p) method in both gas and DMSO phases. Experimental results from powder XRD and reported single crystal XRD showed excellent agreement. The experimental FT-IR and FT-Raman spectra correlated well with theoretical vibrational frequencies, and UV-Vis spectra comparisons further validated the computational findings. Molecular electrostatic potential (MEP), Mulliken and natural charges, and Fukui function analyses highlighted the reactive regions of 4AMP. Natural bond orbital (NBO) analysis revealed stabilization energies of bonding and antibonding orbitals. Hirshfeld surface and fingerprint analyses provided insights into intra and intermolecular interactions. Biological studies indicated that 4AMP exhibited the strongest binding affinity towards the PI3Kα (PIK3CA catalytic subunit) at -6.9 kcal/mol, suggesting significant therapeutic potential. Molecular dynamics simulations over 100 ns have been performed to assess the stability and dynamic behaviour of 4AMP. Cytotoxicity assays demonstrated potent activity against breast cancer cell lines, with IC₅₀ values of 16.89 μg/mL (MCF-7) and 19.53 μg/mL (MDA-MB-231). These findings suggest that 4AMP possesses promising anticancer activity, combining favourable structural, spectroscopic, and biological characteristics, making it a potential candidate for targeted breast cancer therapy.