A Solid-State NMR Study of the Antibacterial Drug Cefpodoxime Proxetil

Abstract The structure-activity relationship of various molecular moieties of cefpodoxime proxetil is described by measuring Chemical shift anisotropy (CSA) tensor, spin-lattice relaxation time and molecular correlation time at twenty one crystallographically different carbon nuclei sites. Cefpodoxime proxetil molecule is associated with three rings, the aminothiazole ring, β-lactam ring, and the dihydrothiazine ring, which provide stability to the drug molecule towards β-lactamases and increase the affinity of the drug to PBPs receptors. A large variation of CSA parameters and motional degrees of freedom are observed among carbon nuclei reside on these three rings, which implies that the electronic environment, molecular conformation, and molecular dynamics are altered substantially within the ring. The substitution at the C7 position of the β-lactam ring (like acyl side chain, oxime group, and aminothiazole ring) is responsible for semi-synthetic incorporation. It also influences the antibacterial activity and the binding affinity of the drug with β-lactamase. A huge variation of the spin-lattice relaxation time and molecular correlation time is observed in this region. These types of description of the structure-activity relationship of the antibacterial drug cefpodoxime proxetil will be beneficial for developing the advanced antibacterial drugs, and it will also be useful in NMR crystallography.