Solid state synthesis of zwitterionic cocrystal 5-fluorouracil L-phenylalanine explicated via structural, spectroscopy, quantum chemicals, Hirshfeld and docking analysis

Abstract

The single crystal 5-Fluorouracil l-phenylalanine (5FUPA) was synthesized using solid state technique and crystallized at room temperature using the slow evaporation method. The crystal with orthorhombic structure and P212121 space group was obtained. Quantum chemical studies were used to compute the structural parameters and various spectroscopic properties for 5FUPA using the B3LYP/6–311++G (d, p). The structural parameters from reported single crystal XRD and calculated from DFT were compared, and they were showing good agreement with each other. The peaks obtained by experimental FTIR and modes calculated by theoretical DFT method have a good degree of consistency. The UV–Visible absorption spectrum of 5FUPA shown to have maximum absorption peak at 266 nm. The NBO analysis was used to calculate the interaction between bonding and anti-bonding orbitals and their stabilization energy in 5FUPA. The most reactive sites of the 5FUPA cocrystal were investigated by Fukui function descriptor and Molecular Electrostatic Potential (MEP) energy surface calculated using Mulliken charges. Inter- and intra-molecular interactions of the 5FUPA were investigated using the Hirshfeld surface and finger print methods. The topological studies ELF, LOL and thermodynamic parameters at different temperatures were performed. The molecular docking outcomes indicate that, cocrystal 5FUPA have better inhibitory effects on breast cancer proteins when compared to 5-fluorouracil and l-phenylalanine. The 5FUPA cocrystal has performed better compared to the other two molecules in terms of docking affinity, having a better binding score range of -8.3 kcal/mol to -9.4 kcal/mol. This demonstrates that 5FUPA cocrystal has unveiled more bioactivity and reactivity when compared with 5-fluorouracil and l-phenylalanine, and can be further considered as a breast cancer medication after clinical trials.