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

Abstract

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.