A combined spectroscopic and quantum chemical approach to study the molecular interaction between anti-inflammatory drug Hydrocortisone and amino acid L-Phenylalanine

The work presented in the manuscript addresses the molecular interaction of Hydrocortisone with L-Phenylalanine accomplished by density functional theory (B3LYP/6-311 G(d,p)), and spectroscopic approaches such as Raman, SERS, FTIR, and Powder X-ray diffraction (PXRD) methods. Raman and FTIR spectra are collected and compared with the theoretically obtained data and they support each other. Insight into the delocalization scheme of the Hydrocortisone + L-Phenylalanine complex reveals the formation of C=O center dot center dot center dot H intermolecular hydrogen bond. The characterization of the intermolecular interaction by AIM and RGD-NCI analysis demonstrates the presence of both electrostatic and covalent nature. Molecular electrostatic potential mapped and low FMO's gap (-4.99 eV) unveil the reactive nature of the interacting complex. The aqueous solubility assessment of the synthesized complex exhibits almost 2.95 times better solubility as compared to Hydrocortisone. Mulliken atomic charges and thermodynamic parameters are enumerated with B3LYP/6-311 G(d,p) level. The calculated bioactivity score and drug-likeness parameters show good oral bioavailability of the complex. In addition, molecular docking study performed with the target proteins JAK1 (PDB ID: 6DBN) shows binding affinity of -9.43 kcal/mol.