Investigation of the Detailed Internal Structure and Dynamics of Itraconazole by Solid-State NMR Measurements

[Image: see text] The structure and dynamics of itraconazole were investigated by (13)C 2DPASS MAS SSNMR and spin-lattice relaxation time measurement to get an insight into its multiple biological activities, e.g., antifungal, antiviral, anticancer activities, etc. The molecular correlation time at chemically different sites of carbon nuclei was calculated by considering that the spin-lattice relaxation mechanism is mainly dominated by chemical shift anisotropy interaction and heteronuclear dipole–dipole interaction. The spin-lattice relaxation time is long for C35, C6, C5, and C34 carbon nuclei that participated in the 1, 2, 4-triazole ring. On the contrary, it is comparatively shorter for C1, C2, C3, and C4 carbon nuclei associated with the sec-butyl group in the triazolane side-chain region. Chemical shift anisotropy (CSA) parameters of C5, C6, C34, and C35 nuclei are much higher than those of C1, C2, C3, C4 nuclei, indicating that the relaxation mechanism at a high value of magnetic field is predominated by chemical shift anisotropy interaction. The molecular correlation time of carbon nuclei residing at the side-chain region is 2–3 orders of magnitude lesser than that of those participated in the 1,2,4-triazole ring. The spin-lattice relaxation time is very long for carbon nuclei C28 and C30 bonded with chlorine. Asymmetry and anisotropy parameters are also very high for the spinning CSA sideband pattern corresponding to the C28 and C30 nuclei. The molecular correlation time is on the order of 10(–3) s for C28 and 10(–4) s for C30, whereas for side-chain carbon nuclei, it is on the order of 10(–6) s. This suggests that the effective magnetic field experienced by C28 and C30 nuclei is affected by the polarization of the chemical bond. A huge variation in molecular correlation time is observed for chemically different sites of carbon nuclei of the itraconazole molecule. These investigations vividly portrayed how the structure is correlated with the dynamics of a valuable drug, itraconazole, with multiple biological activities. This study will enlighten the way of inventing advance medicine for multiple biological activities in the pharmaceutical industry.