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1.
Pharmaceutics ; 15(6)2023 May 23.
Article in English | MEDLINE | ID: mdl-37376020

ABSTRACT

Viral and synthetic vectors to deliver nucleic acids were key to the rapid development of extraordinarily efficient COVID-19 vaccines. The four-component lipid nanoparticles (LNPs), containing phospholipids, PEG-conjugated lipids, cholesterol, and ionizable lipids, co-assembled with mRNA via a microfluidic technology, are the leading nonviral delivery vector used by BioNTech/Pfizer and Moderna to access COVID-19 mRNA vaccines. LNPs exhibit a statistical distribution of their four components when delivering mRNA. Here, we report a methodology that involves screening libraries to discover the molecular design principles required to realize organ-targeted mRNA delivery and mediate activity with a one-component ionizable multifunctional amphiphilic Janus dendrimer (IAJD) derived from plant phenolic acids. IAJDs co-assemble with mRNA into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions, via the simple injection of their ethanol solution in a buffer. The precise location of the functional groups in one-component IAJDs demonstrated that the targeted organs, including the liver, spleen, lymph nodes, and lung, are selected based on the hydrophilic region, while activity is associated with the hydrophobic domain of IAJDs. These principles, and a mechanistic hypothesis to explain activity, simplify the synthesis of IAJDs, the assembly of DNPs, handling, and storage of vaccines, and reduce price, despite employing renewable plant starting materials. Using simple molecular design principles will lead to increased accessibility to a large diversity of mRNA-based vaccines and nanotherapeutics.

2.
Heliyon ; 9(1): e12492, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36699273

ABSTRACT

Herein, a new series of azo ligands HL-1 (5-(2-chloro-6-(phenylcarbonyl)phenyl)diazenyl)-6-hydroxydihydropyrimidines-2,4dione), HL-2 (5-(2-chloro-6-(phenylcarbonyl)phenyl)diazenyl)-6-hydroxy-2-thioxottetrahydropyrimidin-4one), HL-3 (5-(2,4-dichloro-6-(phenylcarbonyl)phenyl) diazenyl)-6-hydroxydihydropyrimidines-2,4dione), HL-4 (5-(2,4-dichloro-6-(phenylcarbonyl) phenyl)diazenyl)-6-hydroxy-2-thioxotetrahydropyrimidin-4one) and their metal complexes with Cu(II) & Ni(II) were synthesized successfully having excellent yield, in reproducible conditions and for structure elucidation different advance spectroscopic techniques (FTIR, 1H NMR, 13C NMR and Mass Spectrometry) were applied. In FTIR analysis, the absence of peak at 3450-3550 cm -1 due to -NH2 and presence of a new peak of N=N at 1390-1520 cm-1 confirmed synthesis of the ligands. The 1H NMR spectra of azo ligands showed singlet peak at 11.5-13.5 ppm (Ar-OH) for hydroxyl group and -NH2 signals disappearance of anilines at 4-5 ppm also gives strong indication for the synthesis of azo compounds. On complexation two most important peaks (M-O, M-N) appeared in all the metal chelates in the range of 400-600 cm-1 which were not present in any of the ligands, confirmed the formation of complexes. Molecular ion peaks in mass spectra at 273, 388, 407 and 423 m/z value for ligands as well as for complexes at 803, 835, 871 and 904 m/z also give strong indication that proposed ligands and their metal complexes are produced successfully. Biological screening of the synthesized compounds were also carried out against different bacterial strains (E.coli, S.typhi, and B.subtilis), antifungal (C.albicans, A.niger, and C.glabrata) strains and antioxidant activity. From results it was observed that HL-4 and Cu complexes exhibited maximum inhibition against all bacterial and fungal strains as compared to other ligands and standard drug.

3.
Heliyon ; 8(10): e10936, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36276714

ABSTRACT

The present study is aimed at adsorptive removal of Mercury (Hg2+) using highly functionalized nanomaterials based on Graphene Oxide Zeolitic Imidazolate Framework composite (ZIF-67@GO). Solvothermal methodology was used to synthesize ZIF-67@GO composite. Synthesized compounds were confirmed by FTIR, SEM, PXRD and EDX analysis. The as-prepared ZIF-67@GO was tested as efficient adsorbent for effective removal of Mercury (Hg2+) from aquatic environment. The atomic adsorption spectrophotometer was used to monitor the process of adsorption of Hg+2 on ZIF-67@GO. From the adsorption data, the maximum removal efficiency achieved was 91.1% using 10 mg amount of composite for 50 mL using 20 ppm Mercury (Hg2+) solution. Different parameters like pH, contact time, concentration, adsorption kinetics and isotherm were also examined to explore adsorption process. Adsorption data fitted well for Freundlich Model having R2 value of 0.9925 than Langmuir Isotherm with R2 value of 0.9238. Kinetics were rapid and excellently described via 2nd order model with R2 = 0.99946 than 1st order model with R2 value of 0.8836. Freundlich and pseudo 2nd order models validated that multilayer chemisorption occurs during adsorption process due to the presence of highly functionalized sites on ZIF-67@GO composite. The synthesized composite material has shown excellent reusability. Thus, water stable ZIF-67@GO composites can efficiently be used for Mercury (Hg2+) confiscation from water.

4.
Food Chem Toxicol ; 149: 112008, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33508417

ABSTRACT

Heavy metals especially lead (Pb) and mercury (Hg) are recognized as most emerging pollutants in underground water and are major threat to public health around the world. Major challenge to mitigate water pollution is construction of effective materials containing a host of deceivingly accessible high-density and high-level efficiency. Herein, we have synthesized two metal-organic frameworks (MOFs) with efficient porosity showing the right combination of structures. Representatively, ZIF-8 and ZIF-67 were designed by reacting Zn, Co salts with 2-methyl imidazole showing superior efficacy in removing Pb and Hg (1978.63&1436.11 mg/g respectively) from water. These adsorbents displayed high distribution values permitting them to quickly reduce concentration level of Pb2+, Hg2+ below permissible limit (Pb = 0-15 µg/L, Hg = 1-10 µg/L). EDX, FTIR analysis revealed that Pb2+, Hg2+ bound through weak interactions. Results presented here have shown extraordinary potential with high environmental remediation performance having 99.5% and 98.1% removal efficiency for lead & mercury respectively. Results revealed that adsorbents have same organic linker that identifies same morphology required for adsorption. The difference in adsorption capacity and porosity (ZIF-8 = 937&1370 m2/g, ZIF-67 = 1289&1889 m2/g) are deliberately caused due to presence of metal atoms having different electronic distribution, as cobalt in ZIF-67 and in case of ZIF-8 zinc metal.


Subject(s)
Imidazoles/chemistry , Lead/chemistry , Mercury/chemistry , Metal-Organic Frameworks/chemistry , Water Pollutants, Chemical/chemistry , Water/chemistry , Adsorption , Kinetics , Microscopy, Electron, Scanning , Water Purification
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