Analyzing atomic scale structural details and nuclear spin dynamics of four macrolide antibiotics: erythromycin, clarithromycin, azithromycin, and roxithromycin.

The current investigation centers on elucidating the intricate molecular architecture and dynamic behavior of four macrolide antibiotics, specifically erythromycin, clarithromycin, azithromycin, and roxithromycin, through the application of sophisticated solid-state nuclear magnetic resonance (SSNMR) methodologies. We have measured the principal components of chemical shift anisotropy (CSA) parameters, and the site-specific spin-lattice relaxation time at carbon nuclei sites. To extract the principal components of CSA parameters, we have employed 13C 2DPASS CP-MAS SSNMR experiments at two different values of magic angle spinning (MAS) frequencies, namely 2 kHz and 600 Hz. Additionally, the spatial correlation between 13C and 1H nuclei has been investigated using 1H-13C frequency switched Lee-Goldburg heteronuclear correlation (FSLGHETCOR) experiment at a MAS frequency of 24 kHz. Our findings demonstrate that the incorporation of diverse functional groups, such as the ketone group and oxime group with the lactone ring, exerts notable influences on the structure and dynamics of the macrolide antibiotic. In particular, we have observed a significant decrease in the spin-lattice relaxation time of carbon nuclei residing on the lactone ring, desosamine, and cladinose in roxithromycin, compared to erythromycin. Overall, our findings provide detailed insight into the relationship between the structure and dynamics of macrolide antibiotics, which is eventually correlated with their biological activity. This knowledge can be utilized to develop new and more effective drugs by providing a rational basis for drug discovery and design.

Synergetic impact of MgO on PMMA-ZrO2 hybrid composites: Evaluation of structural, morphological and improved mechanical behavior for dental applications.

This work aims to demonstrate the effect of ZrO2 and MgO inclusion into the Poly(methyl methacrylate) (PMMA). To fabricate novel hybrid composites via heat cure method, various composites (PZM2, PZM4 and PZM6) were synthesized in the system [(95-x) PMMA + 5 ZrO2 + x MgO] (x = 2, 4, and 6) respectively. Density of the prepared composites were determined and varying between 1.035-1.152 g/cm3. X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) followed by EDAX and mechanical testing were performed to evaluate the fabricated composite properties. Moreover, to explore the structure of the fabricated composites the 13 C CP-MAS SSNMR and 1 H-13 C Phase-Modulated Lee Goldberg (PMLG) HETCOR Spectrum were recorded which clarify chemical shifting and motional dynamics of the composites. Mechanical tests were performed by UTM and the obtained parameters such as compressive strength, Young's modulus, fracture toughness, brittleness coefficient, flexural strength and flexural modulus are found to be in the range of 91-100 MPa, 0.48-0.51 GPa, 9.122-9.705 MPa.m1/2, 0.66-0.815, 51.03-42.78 MPa and 499-663 MPa respectively. Some more mechanical parameters such as proportional limit, elastic limit, failure strength, modulus of resilience and modulus of toughness were also calculated. Furthermore, tribological properties were also determined and the coefficient of friction (COF) was decreased by 17.4 % and 38 % for composite PZM6 at 20 N and 40 N as compared to the composite PZM2 and the lowest wear volume of 1.55 mm3 was observed for PZM2, whereas the maximum volume loss of 5.64 mm3 is observed for composite PZM6. To check out the biocompatibility, cytotoxicity and genotoxicity of the fabricated composites the Trypan-blue assay was also performed for PZM2 and PZM6 composites. Dissection on the gut of larvae was also performed on the both composites followed by DAPI and DCFH-DA staining. Therefore, these synthesized samples can be used for the fabrication of denture materials.

Atomic-Scale Resolution Insights into Structural and Dynamic Differences between Ofloxacin and Levofloxacin.

This study employs advanced solid-state NMR techniques to investigate the atomic-level structure and dynamics of two enantiomers: ofloxacin and levofloxacin. The investigation focuses on critical attributes, such as the principal components of the chemical shift anisotropy (CSA) tensor, the spatial proximity of 1H and 13C nuclei, and site-specific 13C spin-lattice relaxation time, to reveal the local electronic environment surrounding specific nuclei. Levofloxacin, the levo-isomer of ofloxacin, exhibits higher antibiotic efficacy than its counterpart, and the dissimilarities in the CSA parameters indicate significant differences in the local electronic configuration and nuclear spin dynamics between the two enantiomers. Additionally, the study employs the 1H-13C frequency-switched Lee-Goldburg heteronuclear correlation (FSLGHETCOR) experiment to identify the presence of heteronuclear correlations between specific nuclei (C15 and H7 nuclei and C13 and H12 nuclei) in ofloxacin but not in levofloxacin. These observations offer insights into the link between bioavailability and nuclear spin dynamics, underscoring the significance of NMR crystallography approaches in advanced drug design.