Understanding the structure and dynamics of anti-inflammatory corticosteroid dexamethasone by solid state NMR spectroscopy

For decades corticosteroid dexamethasone has been applied as an anti-inflammatory, immunosuppressant, and decongestant, in the prevention of postoperative nausea and vomiting (PONV), and for auto-immune diseases, allergic reactions, total hip arthroplasty (THA), and cancer. Recently in vitro studies suggested that it may be beneficial to deal with the COVID-19 pandemic. This important drug molecule was investigated by solid state NMR measurements to provide more complete features of its structure and dynamics at atomic scale resolution. The spin–lattice relaxation time at twenty-two different carbon sites of dexamethasone was determined by the Torchia CP method. The principle components of the chemical shift anisotropy tensor were determined by (13)C two-dimensional phase adjusted spinning sideband (2DPASS) cross-polarization magic angle spinning (CP-MAS) solid state NMR experiments. The molecular correlation time at twenty-two crystallographically different carbon sites of dexamethasone was calculated by considering that the spin–lattice relaxation mechanism of the (13)C nucleus is mainly governed by the chemical shift anisotropy interaction and the heteronuclear dipole–dipole coupling. The spin–lattice relaxation time of carbon nuclei resides on ‘A’, ‘B’, ‘C’, and ‘D’ rings and the side-chain of dexamethasone is quite large, which implies the close-packed arrangement of the molecule. The difference in molecular correlation time at various regions of the molecule demonstrates the existence of different degrees of freedom within the molecule. This may be the reason for the various biological activities exhibited by the molecule. These types of detailed features of the structure and dynamics of such an important drug with multiple biological activities are necessary to develop the advanced medicine and it will also help to understand the structure–activity relationships of corticosteroid.