Study the Structure and Dynamics of Antifungal Agent Ketoconazole by CSA and Site-Specific Spin-Lattice Relaxation Time Measurements

An azole antifungal agent, ketoconazole, is widely used in the treatment of mucosal fungal infections related to AIDS immunosuppression, organ transplantation, and cancer chemotherapy. The structure and dynamics of ketoconazole are thoroughly studied by chemical shift anisotropy tensor and site-specific spin-lattice relaxation time measurements. The molecular correlation time at crystallographically different carbon sites is calculated by considering that the spin-lattice relaxation mechanism for the 13C nucleus is mainly governed by chemical shift anisotropy interaction and hetero-nuclear dipole-dipole coupling. The CSA parameters at the crystallographically distinct sites of ketoconazole are determined by two-dimensional phase adjusted spinning sideband (2D PASS) cross-polarization magic angle spinning (CP-MAS) solid-state NMR experiment. The site-specific spin-lattice relaxation time is measured by the Torchia CP experiment. The spin-lattice relaxation rate is slow for all the carbon nuclei sites except C2, C3, C4, C5, and C26 carbon nuclei reside on the piperazine ring and the methyl group. It suggests the close-pack arrangement of the molecule due to π-π stacking interaction. The molecular correlation time of all the carbon atoms reside on the benzene ring, 1,3-dioxolane ring, imidazole ring, and the 2,4-dichlorobenzene ring is of the order of 10-4 s, while it is of the order of 10-7 s for carbon atoms reside on the piperazine ring. The CSA parameters of the carbon nuclei on the piperazine ring (C2, C3, C4, C5), and the methyl group (C26) are very low compared to other carbon nuclei. The CSA parameters are very high for carbon nuclei reside on the benzene ring, imidazole ring, and the 2,4-dichlorobenzene ring due to the presence of π-electrons. A huge variation of the spin-lattice relaxation time and the molecular correlation time are observed for numerous carbon nuclei situated on the side-chain of ketoconazole. The spin-lattice relaxation time varies from 500 s to 8 s, and the molecular correlation time varies in the range of 10-4s to 10-7s. These types of investigations portrayed the correlation between the structure and dynamics of the antifungal drug ketoconazole, which will help to develop the advanced antifungal drugs. Additionally, the CSA information of the drug molecules will be immensely useful for NMR crystallography.

Determination of the correlation between the structure and dynamics of deflazacort by solid state NMR measurements

The correlation between the structure and dynamics of glucocorticoid deflazacort is determined by a 2DPASS CP-MAS SSNMR experiment and 13C spin–lattice relaxation time by a Torchia CP experiment.

A Microcontroller System for the Automation of Transient Effect Determination of the Spin-Lattice Relaxation Time Using Continuous Wave NMR

A simple transient effect method for the determination of the spin-lattice relaxation time using continuous wave NMR (TEDSpiL) with a marginal oscillator was recently reported (doi:10.1002/mrc.4594). Such a system measures a parameter called Tx that is related to T1 and allows T1 to be determined with the aid of calibration samples. For such a system, the process of making the Tx measurement does not require variable parameters and so is ideal for implementing in microcontroller code. In this article, we demonstrate that TEDSpiL may be automated using two microcontrollers from the Teensy family to make a low power and portable system.