Vibrational spectroscopic studies, normal co-ordinate analysis, first order hyperpolarizability, HOMO–LUMO of midodrine by using density functional methods

• FTIR, FT-Raman and UV–Vis investigations of MIDODRINE were carried out.
• Molecular structure was studied using DFT/6-311++G(d,p)method.
• The PED calculation provides a strong support for the frequency assignment.
• NBO analysis used to explain the interaction between electron donors and acceptors.

The FTIR (4000–400 cm−1), FT-Raman (4000–100 cm−1) and UV–Visible (400–200 nm) spectra of midodrine were recorded in the condensed state. The complete vibrational frequencies, optimized geometry, intensity of vibrational bands and atomic charges were obtained by using Density Functional Theory (DFT) with the help of 6-311++G(d,p) basis set. The first order hyperpolarizability (β) and related properties (μ, α and Δα) of this molecular system were calculated by using DFT/6-311++G(d,p) method based on the finite-field approach. The assignments of the vibrational spectra have been carried out with the help of Normal Co-ordinate Analysis (NCA) following the scaled quantum mechanical force methodology. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using NBO analysis. From the recorded UV–Visible spectrum, the electronic properties such as excitation energies, oscillator strength and wavelength are calculated by DFT in water and gas methods using 6-311++G(d,p) basis set. The calculated HOMO and LUMO energies confirm that charge transfer occurs within the molecule. Besides MEP, NLO and thermodynamic properties were also calculated and interpreted. The electron density-based local reactivity descriptor such as Fukui functions was calculated to explain the chemical selectivity or reactivity site in midodrine.

Midodrine is a prodrug acting as α-adrenergic agonist useful in the treatment of neurogenic orthostatic hypotension. An extensive work has been carried out on the title compound and its derivatives in recent year. At present, vibrational spectroscopy is used not only for functional group identification of organic compounds, but also to investigate the molecular conformation, reaction kinetics.Figure optionsDownload as PowerPoint slide