Chemical alterations to murine brain tissue induced by formalin fixation: implications for biospectroscopic imaging and mapping studies of disease pathogenesis

Understanding biochemical mechanisms and changes associated with disease conditions and, therefore, development of improved clinical treatments, is relying increasingly on various biochemical mapping and imaging techniques on tissue sections. However, it is essential to be able to ascertain whether the sampling used provides the full biochemical information relevant to the disease and is free from artefacts. A multi-modal micro-spectroscopic approach, including FTIR imaging and PIXE elemental mapping, has been used to study the molecular and elemental profile within cryofixed and formalin-fixed murine brain tissue sections. The results provide strong evidence that amino acids, carbohydrates, lipids, phosphates, proteins and ions, such as Cl(-) and K(+), leach from tissue sections into the aqueous fixative medium during formalin fixation of the sections. Large changes in the concentrations and distributions of most of these components are also observed by washing in PBS even for short periods. The most likely source of the chemical species lost during fixation is the extra-cellular and intra-cellular fluid of tissues. The results highlight that, at best, analysis of formalin-fixed tissues gives only part of the complete biochemical "picture" of a tissue sample. Further, this investigation has highlighted that significant lipid peroxidation/oxidation may occur during formalin fixation and that the use of standard histological fixation reagents can result in significant and differential metal contamination of different regions of tissue sections. While a consistent and reproducible fixation method may be suitable for diagnostic purposes, the findings of this study strongly question the use of formalin fixation prior to spectroscopic studies of the molecular and elemental composition of biological samples, if the primary purpose is mechanistic studies of disease pathogenesis.     

Electrochemical study of the corrosion inhibition ability of “smart” coatings applied on AA2024

Smart epoxy coatings modified with different additives were applied on AA2024. The following three different systems were studied: a reference consisting of an epoxy coating containing chromate active pigments and two “smart” coatings modified with containers loaded with corrosion inhibitor—layered double hydroxides filled with mercaptobenzothiazole and tubular halloysites (HS) filled with 8-hydroxyquinoline. The thickness of the coatings was determined by scanning electron microscopy. The barrier properties and the average corrosion resistance were assessed by electrochemical impedance spectroscopy (EIS). The long-term corrosion repair ability of the various coatings was confirmed by EIS measurements carried for a period of 3 weeks in scratched samples. The ability of the smart additives to inhibit corrosion over defects with different sizes and geometry was studied at the microscale by using localized impedance spectroscopy (LEIS) and the scanning vibrating electrode technique. The results demonstrate that the additives provide effective corrosion inhibition on defects of various sizes. Moreover, the LEIS measurements give some important highlights concerning the mechanisms and kinetics of inhibition of each system.     

Mécanismes de Formation d'α-Aminophosphonates

When di-n-decylphosphonate 1a or di-benzylphosphite 1b are reacted with furan imine 2a or thiophenic imine 2b , the reaction leads to an f -aminophosphonate: 3a , 3b , or 3c following an ion- or radical-based reaction.     

Removal of Cu(II), Cd(II) and Cr(III) ions from aqueous solution by dam silt

The removal of heavy metals, such as Cu(II), Cd(II) and Cr(III) from aqueous solution was studied using Chorfa silt material (Mascara, Algeria). The main constituents of silt sediment are quartz, calcite and mixture of clays. The experimental data were described using Freundlich, Langmuir, Dubinin–Radushkevich (D–R) and Langmuir–Freundlich models. The adsorbed amounts of chromium and copper ions were very high (95% and 94% of the total concentration of the metal ions), whereas cadmium ion was adsorbed in smaller (55%) amounts. The Langmuir–Freundlich isotherm model was the best to describe the experimental data. The maximum sorption capacity was found to be 26.30, 11.76 and 0.35 mg/g for Cr³⁺, Cu²⁺ and Cd²⁺, respectively. The results of mean sorption energy, E (kJ/mol) calculated from D–R equation, confirmed that the adsorption of copper, chromium and cadmium on silt is physical in nature.     

Application of butenonyl-C-glucosides in the synthesis of pyrazolinyl-, aminopyrimidinyl- and biphenyl methyl-��-d-C-glucopyranosides

An access to different glycohybrids involving nucleophilic addition of N- and C-nucleophiles to the butenonyl glycosides followed by cyclization and subsequent reactions is reported. In the present communication, three different prototypes, β-D-glucopyranosylmethyl pyrazolines, β-D-glucopyranosylmethyl pyrimidines and β-D-glucopyranosylmethyl biphenyls, were prepared in moderate to good yields.     

Synthesis,characterization and self-assembly of amphiphilic block copolymer poly(4-vinyl benzene chloride)-b-poly(N-vinylpyrrolidone) in aqueous solution

The synthesis, characterization and self-assembly of a novel amphiphilic block copolymer containing a poly(N-vinylpyrrolidone) as a segment of hydrophilic and poly(4-vinyl benzene chloride) (PVBC) arms are reported. The copolymer was characterized by FT-IR spectroscopy ¹H NMR. The composition and the molecular weights of the block copolymers were established using gel permeation chromatography and ¹H NMR. The water-soluble fraction of poly(N-vinyl-2-pyrrolidone) (PVP)/PVBC block copolymers formed micelles which were investigated at 25 °C in water at 5 mg/ml concentration using a tensiometer. The morphology of micelles in aqueous solution was determined by the AFM, SANS, and SAXS methods.     

Core-Modified Coelenterazine Luciferin Analogues: Synthesis and Chemiluminescence Properties

In this work on the design and studies of luciferins related to the blue-hued coelenterazine, the synthesis of heterocyclic analogues susceptible to produce a photon, possibly at a different wavelength, is undertaken. Here, the synthesis of O-acetylated derivatives of imidazo[1,2-b]pyridazin-3(5 H)-one, imidazo[2,1-f][1,2,4]triazin-7(1 H)-one, imidazo[1,2-a]pyridin-3-ol, imidazo[1,2-a]quinoxalin-1(5 H)-one, benzo[f]imidazo[1,2-a]quinoxalin-3(11 H)-one, imidazo[1′,2′:1,6]pyrazino[2,3-c]quinolin-3(11 H)-one, and 5,11-dihydro-3 H-chromeno[4,3-e]imidazo[1,2-a]pyrazin-3-one is described thanks to extensive use of the Buchwald–Hartwig N-arylation reaction. The acidic hydrolysis of these derivatives then gave solutions of the corresponding luciferin analogues, which were studied. Not too unexpectedly, even if these were “dressed” with substituents found in actual substrates of the nanoKAZ/NanoLuc luciferase, no bioluminescence was observed with these compounds. However, in a phosphate buffer, all produced a light signal, by chemiluminescence, with extensive variations in their respective intensity and this could be increased by adding a quaternary ammonium salt in the buffer. This aspect was actually instrumental to determine the emission spectra of many of these luciferin analogues.     

De novo design of chiral organotin cancer drug candidates: validation of enantiopreferential binding to molecular target DNA and 5'-GMP by UV-visible, fluorescence, (1)H and (31)P NMR

N,N-bis[(R-/S-)-1-benzyl-2-ethoxyethane] tin (IV) complexes were synthesized by applying de novo design strategy by the condensation reaction of (R-/S-)2-amino-2-phenylethanol and dibromoethane in presence of dimethyltin dichloride and thoroughly characterized by elemental analysis, conductivity measurements, IR, ESI-MS, (1)H, (13)C and (119)Sn, multinuclear NMR spectroscopy and XRD study. Enantioselective and specific binding profile of R-enantiomer 1 in comparison to S-enantiomer 2 with ultimate molecular target CT-DNA was validated by UV-visible, fluorescence, circular dichroism, (1)H and (31)P NMR techniques. This was further corroborated well by interaction of 1 and 2 with 5'-GMP.     

Electrochemically and photochemically active Palladium(II) heterotopic metallacalix[3]arenes

The cyclic trinuclear system, [(en)(3)Pd(3)(4,7-phen)(3)](6+), undergoes a ligand exchange reaction with 5-R-2-hydroxypyrimidine derivatives (HRpymo; R = ethynylferrocene, 5-(dimethylamino)-N-(2-propynyl)-1-naphthalene sulfonamide) to give [(en)(3)Pd(3)(4,7-phen)(2)(Rpymo)](5+), functional supramolecular receptors of mononucleotides.     

(1-Naphthyl)(trifluoromethyl) O-carboxy anhydride as a chiral derivatizing agent: eclipsed conformation enforced by hydrogen bonding

The preparation of the (1-naphthyl)(trifluoromethyl) O-carboxy-anhydride 1 and its use as a chiral derivatizing agent with several alpha-chiral primary amines are reported. The very large Delta delta(RS) values observed in (1)H NMR have been correlated with a marked preference of the corresponding alpha-hydroxy-amides for the eclipsed conformation. In comparison, the related O-methylated amides are shown to adopt staggered conformations, which substantiates the critical role of intramolecular hydrogen bonding in maximizing the anisotropic effect.