DFT and TD-DFT insights into the conformational, electronic, and spectral properties of purine-based glycol nucleic acid (GNA) monophosphates and their Zn(II) coordination effects.

The structurally simpler Glycol nucleic acids (GNAs) have been known to be chemically robust alternatives to canonical nucleic acids, but their conformational and electronic properties remain underexplored. In this work, density functional theory (DFT), time-dependent DFT (TD-DFT), and molecular docking were applied to purine-based GNAs and their Zn(II) complexes. Conformational analysis reveals alternative low-energy conformers with opposite nucleobase orientation relative to their crystal geometries. The Zn(II) coordination leads to reduction of orbital energy gap and increases dipole moment enhancing polarity and electron affinity of the GNA system. UV-vis analysis further identifies λmax between 189 and 255 nm in conformers. The NCI and QTAIM analyses were also performed to identify weak interactions and nature of bonding in the systems. Molecular docking analysis suggests conformational-dependent protein-ligand interactions and demonstrate slightly favorable binding score for metal complexes. The binding energy of the complexes using MM/GBSA-based free energy calculations suggest stability trend of- GG1Z > GA2Z > GA1Z > GG2Z. Collectively, these insilico results showcase a new conformational adaption of nucleobase geometry in GNA along with QM-derived electronic, vibrational, and optical properties of the conformers and reveals their potential as tunable synthetic scaffolds for biomolecular design.