Antihypotensive potency of p-synephrine: Spectral analysis, molecular properties and molecular docking investigation

•At 6-311++g(2d,2p) level of theory, PBE0 at 4.085 eV and TPSS at 4.266 eV indicates a are close energy gap.•The highest stabilization energy of 332.24 kcal.mol−1 was observed for BHandHYLP•ADFD is considered the most accurate.functional that predicts the geometric structural parameter•synephrine showed excellent properties and could be used in the formulation of analeptic and antihypotensive drugs. In this study p-synephrine, a catecholamines that has sympathomimetic potency especially for hypotension management was investigated for the effect of dielectric constant on non-linear optics (NLO), structural benchmarking, population analysis by applying density functional theory (DFT), molecular docking, and spectroscopic and X-ray crystallography technique (FT-IR, Raman, UV–Vis, NMR and XRD). The XRD data at room temperature, indicates crystal structure of p-synephrine to be Lattice yype P, with monoclinic space group P21/c (#14–1) with a = 8.85040 Å, b = 12.11660 Å, c = 9.78200 Å, α = 90.0000°, β =122.5510° and γ = 90.0000° to select the functional that best describe the theoretical properties p-synephrine, a selected functionals; APFD, BHandHLYP, M08HX, PBE0 and TPSSTPSS, all at 6-311++g (2d,2p) same level of theory, geometric structural parameter (bond length, bond angle, and dihedral angle) of the optimized structure was compared to x-ray crystallography pattern. The energy gap (Egap), decreases in the order of PBE0:4.086 ≈ TPSS:4.266 < APFD: 5.874 < M08HX: 6.710 < BHandHLYP: 7.204 eV. NBO analysis, indicates the highest stabilization energy of 332.24 kcal.mol−1 for BHandHYLP due to internal charge transfer of electron from π*C1-C3 donor bond orbital to π*C1-C6 acceptor bond orbital. M08HX indicated the highest NLO parameter, dipole moment at 3.518, Static polarizability of -71.588 a.u and change in static polarizability of 14.318 a.u. and static first hyper polarizability a.u. Experimental and theoretical spectroscopic data indicated a very close agreement. The molecular docking showed that p-synephrine is an excellent candidate for further clinical studies as a antihypotensive candidate due to its higher binding affinity compared to standard drug dobutamine.