Spectroscopic and DFT Investigation of the Phenylalanine–Adenine Molecular Complex: Potential Implications to Prostate Cancer

ABSTRACT Amino acid–nucleobase complexes provide fundamental insights into the mechanisms of biomolecular interactions, particularly those underlying drug–DNA and drug–protein binding. Understanding these interactions is essential for the rational design of therapeutics, especially anticancer agents that target nucleic acids or disrupt key DNA–protein complexes. The second most common disease diagnosed in men globally is prostate cancer (PCa). In this study, we investigate the interaction mechanism in the DL‐phenylalanine‐adenine complex, both of which are known for their anticancer properties and are being investigated as a possible active pharmaceutical ingredient for PCa. Spectroscopic techniques, density functional theory (DFT), and dispersion‐corrected density functional theory (DFT‐D3) methods were employed to elucidate the molecular interactions, hydrogen bonding, and electronic properties of the complex. Analyses such as molecular electrostatic potential mapping, frontier molecular orbitals, NCI‐RDG, NLO, ELF, LOL, and vibrational studies confirm the presence of stable non‐covalent interactions and a strong correlation between theoretical and experimental spectra. XRD analysis reveals the complex's monoclinic crystalline nature, and solubility tests show enhanced adenine solubility upon complexation. Toxicity and drug‐likeness assessments support its potential as a drug candidate. Molecular docking with androgen receptor proteins (1E3G and 3RLJ) yielded strong binding affinities of –8.17 and –8.37 kcal/mol, respectively, indicating that the complex may serve as a promising therapeutic strategy against prostate cancer.