Postsynthetically Modified Cationic, Robust MOF Featuring Selective Separation of Carboxylate-Containing Pharmaceutical Drugs from Water at Neutral pH: Elucidation of the Adsorption Mechanism by Theory and Experiments.

The escalating levels of hazardous pharmaceutical contaminants, specifically nonsteroidal anti-inflammatory drugs (NSAIDs), in groundwater reservoir surfaces and surface waterway systems have prompted substantial scientific interest regarding their potential deleterious effects on both aquatic ecosystems and human health. Extraction of those pollutants from wastewater is quite challenging. Hence, the development of economic, sustainable, and scalable techniques for capturing and removing those pollutants is crucial to ensure water safety. Herein, we demonstrate a physicochemically stable, reusable, porous Hf(IV)-based cationic metal-organic framework (MOF), namely, 1'@MeCl for the aqueous phase adsorption-based removal of NSAIDs (diclofenac, naproxen, ibuprofen) from the wastewater environment. The highly positively charged surface of the 1'@MeCl MOF enables it to selectively extract more than 99% of diclofenac, naproxen, and ibuprofen contaminants within less than 30 s. With fast adsorption kinetics, very high adsorption capacities (Qe) were achieved at neutral pH for diclofenac (482.9 mg/g), naproxen (295.9 mg/g), and ibuprofen (219.5 mg/g). Moreover, the influence of changes in pH and coexisting anions on the adsorption property of the 1'@MeCl MOF was studied. Furthermore, the adsorption efficiency of 1'@MeCl in different real water environments was ensured by performing diclofenac, naproxen, and ibuprofen adsorption from tap, river, and lake water. Moreover, a 1'@MeCl-anchored cellulose acetate-chitosan membrane was developed successfully to demonstrate the membrane-based extraction of diclofenac, naproxen, and ibuprofen from contaminated water. Furthermore, a molecular-level mechanistic study was performed through experimental and computational study to propose the plausible adsorption mechanisms for diclofenac, naproxen, and ibuprofen over the surface of 1'@MeCl.

Metal-Organic-Framework-Based Chemosensor for Ultrafast and Ultrasensitive Detection of Pd2+ Ions in Water, Real Specimens, and Test Strips.

A new ultrasensitive and ultrafast Al(III) metal-organic-framework (MOF)-based probe (1) was constructed to detect Pd2+ ions. Extremely selective recognition of Pd2+ ion was demonstrated by the guest-free compound 1 (called 1') using a fluorescence signal. The quenching in the fluorescence signal was observed due to the weak interaction between the linker alkyne-π bond and Pd2+. The mechanism of isophthalic alkyne-π and Pd2+ interaction was systematically examined with the help of isothermal titration calorimetry (ITC), X-ray photoelectron spectroscopy (XPS), and UV-vis spectroscopy. The response time of the MOF for sensing of Pd2+ was 30 s, which is the lowest response time for MOF-based Pd2+ sensing to date, with an ultralow detection limit (102 nM) and Stern-Volmer constant (4.39 × 103 M-1), evidencing the outstanding ability to sense Pd2+ ion by this probe. The Pd2+ detection limit falls among the lowest values. Activated MOF (1') also showed considerable recyclability up to five steps with a constant sensing ability. In different water resources (Milli-Q water, lake water, river water, and tap water), the probe also showed excellent sensing ability. A paper-strip device was developed for the applicability of our material for the real field sensing application of Pd2+. The relevance of 1' is not only up to Pd2+, but it could also sense palladium in other possible oxidation states.

Reusable MOF-Coated Chitosan@Paper Strip Composite for Real-Time Monitoring of Pesticide Pendimethalin and Organoarsenic Feed Additive Roxarsone Levels in Environmental Water, Food, and Vegetable Samples.

An alarming increase in the use of pesticides and organoarsenic compounds and their toxic impacts on the environment have inspired us to develop a selective and highly sensitive sensor for the detection of these pollutants. Herein, a bio-friendly, low-cost Al-based luminescent metal-organic framework (1')-based fluorescent material is demonstrated that helps in sustaining water quality by rapid monitoring and quantification of a long-established pesticide (pendimethalin) and a widely employed organoarsenic feed additive (roxarsone). A pyridine-functionalized porous aluminum-based metal-organic framework (Al-MOF) was solvothermally synthesized. After activation, it was used for fast (<10 s) and selective turn-off detection of roxarsone and pendimethalin over other competitive analytes. This is the first MOF-based recyclable sensor for pendimethalin with a remarkably low limit of detection (LOD, 14.4 nM). Real-time effectiveness in detection of pendimethalin in various vegetable and food extracts was successfully verified. Moreover, the aqueous-phase recyclable detection of roxarsone with an ultralow detection limit (13.1 nM) makes it a potential candidate for real-time application. The detection limits for roxarsone and pendimethalin are lower than the existing luminescent material based sensors. Furthermore, the detection of roxarsone in different environmental water and a wide pH range with a good recovery percentage was demonstrated. In addition, a cheap and bio-friendly 1'@chitosan@paper strip composite was prepared and successfully employed for the hands-on detection of pendimethalin and roxarsone. The turn-off behavior of 1' in the presence of pendimethalin and roxarsone was examined systematically, and plausible mechanistic pathways were proposed with the help of multiple experimental evidences.

A fluorophore anchored MOF for fast and sensitive sensing of Cu(II) and 3-nitrotyrosine in a physiological medium.

We report the solvothermal synthesis of a dansyl anchored hafnium based fluorescent metal-organic framework (MOF) having the formula [Hf6O4(OH)4(L)6]·H2O·6DMF (H2L = 2-((5-(dimethylamino)naphthalene)-1-sulfonamido)terephthalic acid). The synthesized material showed high fluorescence emission properties as well as high thermal (stable up to 330 °C) and chemical stability. It also exhibited a wide range of pH tolerance as well as a high BET surface area of 703 m2 g-1. The activated MOF showed ultra-fast (detection time < 10 s) and ultra-sensitive sensing properties towards Cu(II) and the biologically important biomarker 3-nitrotyrosine (3-NTyr) in a HEPES medium at a physiological pH of 7.4. Along with high selectivity, very low detection limits of 229 nM and 539 nM were obtained for Cu(II) and 3-NTyr respectively. Furthermore, this probe was utilised for the detection and quantification of Cu(II) and 3-NTyr in biosamples (urine and serum) with very low RSD values (2.3-4.8%). Additionally, this probe was employed to detect the presence of Cu(II) as a pollutant in various environmental water samples. Furthermore, for rapid economic detection of Cu(II), a MOF coated fluorescent paper strip was demonstrated. Thorough mechanistic investigations displayed that a complexometric interaction between Cu(II) and the probe is the main reason for the quenching of fluorescence intensity. This proposed mechanism was well supported by experimental evidence. On the other hand, the FRET mechanism is proposed based on the experimental observations for dynamic quenching of the fluorescence intensity of the probe in the presence of 3-NTyr.

Versatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.

Nutritional deficiency and genetic errors that impair the transport, absorption, and utilization of vitamin B12 (B12) lead to hematological and neurological manifestations. The cblC disease (cobalamin complementation type C) is an autosomal recessive disorder caused by mutations and epi-mutations in the MMACHC gene and the most common inborn error of B12 metabolism. Pathogenic mutations in MMACHC disrupt enzymatic processing of B12, an indispensable step before micronutrient utilization by the two B12-dependent enzymes methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). As a result, patients with cblC disease exhibit plasma elevation of homocysteine (Hcy, substrate of MS) and methylmalonic acid (MMA, degradation product of methylmalonyl-CoA, substrate of MUT). The cblC disorder manifests early in childhood or in late adulthood with heterogeneous multi-organ involvement. This review covers current knowledge on the cblC disease, structure-function relationships of the MMACHC protein, the genotypic and phenotypic spectra in humans, experimental disease models, and promising therapies.

Thiolatocobalamins repair the activity of pathogenic variants of the human cobalamin processing enzyme CblC.

Thiolatocobalamins are a class of cobalamins comprised of naturally occurring and synthetic ligands. Glutathionylcobalamin (GSCbl) occurs naturally in mammalian cells, and also as an intermediate in the glutathione-dependent dealkylation of methylcobalamin (MeCbl) to form cob(I)alamin by pure recombinant CblC from C. elegans. Glutathione-driven deglutathionylation of GSCbl was demonstrated both in mammalian as well as in C. elegans CblC. Dethiolation is orders of magnitude faster than dealkylation of Co-C bonded cobalamins, which motivated us to investigate two synthetic thiolatocobalamins as substrates to repair the enzymatic activity of pathogenic CblC variants in humans. We report the synthesis and kinetic characterization of cysteaminylcobalamin (CyaCbl) and 2-mercaptopropionylglycinocobalamin (MpgCbl). Both CyaCbl and MpgCbl were obtained in high purity (90-95%) and yield (78-85%). UV-visible spectral properties agreed with those reported for other thiolatocobalamins with absorbance maxima observed at 372 nm and 532 nm. Both CyaCbl and MpgCbl bound to wild type human recombinant CblC inducing spectral blue-shifts characteristic of the respective base-on to base-off transitions. Addition of excess glutathione (GSH) resulted in rapid elimination of the ß-ligand to give aquacobalamin (H2OCbl) as the reaction product under aerobic conditions. Further, CyaCbl and MpgCbl underwent spontaneous dethiolation thereby repairing the loss of activity of pathogenic variants of human CblC, namely R161G and R161Q. We posit that thiolatocobalamins could be exploited therapeutically for the treatment of inborn errors of metabolism that impair processing of dietary and supplemental cobalamin forms. While these disorders are targets for newborn screening in some countries, there is currently no effective treatment available to patients.