Microwave-assisted synthesis of a zirconium-based MOF as an efficient catalyst for one-pot synthesis of xanthene derivatives: in silico study as a potential anti-HIV RNA

Abstract

Firstly, construction and characterization of a novel Zr/VitB₃ metal organic framework have been described. The physicochemical analysis and morphological properties of Zr-MOF has been accomplished by IR, SEM, EDX, TEM, and XRD. Cyclic diketones and various aromatic aldehydes were efficiently and ecologically benignly condensed in a single pot, yielding a range of tetrahydroxanthenediones in good to excellent yields. The utilization of a heterogeneous catalyst, solventless conditions, and a straightforward process that is atom-economical and yields low E-factor values are some of the benefits of this multicomponent reaction. The catalyst can be used up to three times and is completely recyclable. Advantages include a clean methodology, high yield, and straightforward catalyst preparation. Additionally, the study investigates the potential binding interactions of Zr-MOF with the HIV-RNA major groove, revealing its exceptional stability and strong binding affinity. The binding energy score of the Zr-MOF with HIV-RNA was found to be remarkably low at -12.32 kcal mol^-1, indicating its potential to significantly outperform the reference molecule, nevirapine, which showed a higher E-score of -4.98 kcal mol^-1. Xanthene derivatives were also evaluated for their binding affinity to the viral major groove, with energy scores ranging from -5.55 to -6.40 kcal mol^-1, further indicating a promising potential for anti-HIV drug design. These findings underscore the potential of Zr-MOF and xanthene derivatives as potent candidates for HIV treatment, surpassing the reference molecule in terms of binding strength.

Fig. 1. Relevant bioactive xanthene-incorporated frameworks.

Scheme 1. Synthesis of 1,8-dioxo-octahydroxanthene derivative (3a) as a model example.

Fig. 2. (a) SEM images of Zr-Vit B₃/MOF nanostructures and (b) SEM image of Zr-Vit B₃/MOF after reuse.

Fig. 3. EDX analysis of Zr-Vit B₃/MOF nanostructures.

Fig. 4. TEM image of Zr-Vit B₃/MOF nanostructures.

Fig. 5. Experimental and simulated XRD of Zr-Vit B₃/MOF nanostructures.

Fig. 6. (a) Zr-Vit B₃/MOF ball-stick crystal structure, (b) Zr-Vit B₃/MOF single crystal structure, (c) Zr-Vit B₃/MOF full crystal structure, and (d) Zr-Vit B₃/MOF crystal lattice.

Fig. 7. IR-spectrum of Zr-Vit B₃/MOF nanostructures.

Scheme 2. A suggested mechanism for the synthesis of 1,8-dioxo-octahydroxanthene derivatives catalyzed by Zr-MOF.

Fig. 8. (a) Reusability effect of Zr-Vit B₃/MOF catalyst and (b) comparing results with HBF₄–SiO₂ catalyst.

Fig. 9. The interaction between 3g and nevirapine HIV-1 RNA.

Fig. 10. (a) The active site in transcriptase liked with 3g, (b) Zr-MOF binding with HIV-RNA groove.

Fig. 11. Pharmacophore calculation.