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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. [ABSTRACT FROM AUTHOR]

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 β-ligand to give aquacobalamin (H 2 OCbl) 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. [Display omitted] • Two new thiolatocobalamins, CyaCbl and MpgCbl, were synthesized and characterized. • CyaCbl and MpgCbl bound to human CblC in a base-off configuration. • CyaCbl and MpgCbl repaired the enzymatic activity of pathogenic variants of CblC. • The novel thiolatocobalamins underwent spontaneous dethiolation by CblC. [ABSTRACT FROM AUTHOR]