Exploring the effect of disease causing mutations in metal binding sites of human ARSA in metachromatic leukodystrophy.

The arylsulfatase A (ARSA) gene is observed to be deficient in patients with metachromatic leukodystrophy (MLD), a type of lysosomal storage disease. MLD is a severe neurodegenerative disorder characterized by an autosomal recessive inheritance pattern. This study aimed to map the most deleterious mutations at the metal binding sites of ARSA and the amino acids in proximity to the mutated positions. We utilized an array of computational tools, including PredictSNP, MAPP, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT, SNAP, and ConSurf, to identify the most detrimental mutations potentially implicated in MLD collected from UniProt, ClinVar, and HGMD. Two mutations, D29N and D30H, as being extremely deleterious based on assessments of pathogenicity, conservation, biophysical characteristics, and stability analysis. The D29 and D30 are located at the metal-interacting regions of ARSA and found to undergo post-translational modification, specifically phosphorylation. Henceforth, the in-depth effect of metal binding upon mutation was examined using molecular dynamics simulations (MDS) before and after phosphorylation. The MDS results exhibited high deviation for the D29N and D30H mutations in comparison to the native, and the same was confirmed by significant residue fluctuation and reduced compactness. These structural alterations suggest that such mutations may influence protein functionality, offering potential avenues for personalized therapeutic and providing a basis for potential mutation-specific treatments for severe MLD patients.

Theoretical investigation, biological evaluation and VEGFR2 kinase studies of metal(II) complexes derived from hydrotris(methimazolyl)borate.

The reaction of soft tripodal scorpionate ligand, sodium hydrotris(methimazolyl)borate with M(ClO4)2·6H2O [MMn(II), Ni(II), Cu(II) or Zn(II)] in methanol leads to the cleavage of B-N bond followed by the formation of complexes of the type [M(MeimzH)4](ClO4)2·H2O (1-4), where MeimzH=methimazole. All the complexes were fully characterized by spectro-analytical techniques. The molecular structure of the zinc(II) complex (4) was determined by X-ray crystallography, which supports the observed deboronation reaction in the scorpionate ligand with tetrahedral geometry around zinc(II) ion. The electronic spectra of complexes suggested tetrahedral geometry for manganese(II) and nickel(II) complexes, and square-planar geometry for copper(II) complex. Frontier molecular orbital analysis (HOMO-LUMO) was carried out by B3LYP/6-31G(d) to understand the charge transfer occurring in the molecules. All the complexes exhibit significant antimicrobial activity against Gram (-ve) and Gram (+ve) bacterial as well as fungal strains, which are quite comparable to standard drugs streptomycin and clotrimazole. The copper(II) complex (3) showed excellent free radical scavenging activity against DPPH in all concentration with IC50 value of 30µg/mL, when compared to the other complexes. In the molecular docking studies, all the complexes showed hydrophobic, π-π and hydrogen bonding interactions with BSA. The cytotoxic activity of the complexes against human hepatocellular liver carcinoma (HepG2) cells was assessed by MTT assay, which showed exponential responses toward increasing concentration of complexes.

Crystal structure of 1-cyclo-propane-carbon-yl-3-methyl-2,6-di-p-tolyl-piperidin-4-one.

The title compound, C24H27NO2, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. The two mol-ecules have very similar conformations and each exhibits an intra-molecular C-H⋯π inter-action. The central piperidine rings adopt boat conformations and the p-tolyl rings are inclined to the mean plane of the piperidine ring by 71.21 (11) and 89.86 (12)° in mol-ecule A and by 68.01 (12) and 89.33 (12)° in mol-ecule B. The cyclopropanecarbonyl group is oriented at an angle of 68.5 (2)° with respect to the mean plane of the piperidine ring in mol-ecule A and 66.2 (2)° in mol-ecule B. In the crystal, the A and B mol-ecules are linked by C-H⋯O hydrogen bonds, enclosing R 2 (1)(6) ring motifs, forming ribbons running along the a-axis direction.

Electrical bistability in conductive hybrid composites of doped polyaniline nanofibers-gold nanoparticles capped with dodecane thiol.

A novel electrical bistable hybrid nanocomposite based on doped Polyaniline nanofibers with 1-Dodecanethiol-protected Gold nanoparticle (PAni.AuDT), 3-4 nm in size, as the conductive component and polystyrene as polymer matrix was prepared. The structural morphology of the composite and the dispersion of nanoparticles inside it were evaluated using Transmission Electron Microscopy (TEM). The thermal stability and the ratio Polyaniline/Gold nanoparticles in the composite were determined by using thermogravimetric analysis. The electrical bistability of the PAni.AuDT-PS composite, the influence of the dispersion of the PAni.AuDT conductive network and the basic operation mechanism, have been assessed by measuring the electrical response of planar device architectures, also as a function of the environmental temperature (in the range 200 K < T < 360 K). The basic operation mechanism of the hybrid compound has been then correlated to the combined action of the thermally-induced scattering of charge carriers and the thermal contraction of the hosting polymeric matrix. Moreover, the right compromise between these two effects in terms of the most efficient bistability has been studied, founding the concentration of the conductive component which optimizes the device on-off ratio (I(on)/ I(off)).