Applications of isotopes in advancing structural and functional heparanomics

Heparanomics is the study of all the biologically active oligosaccharide domain structures in the entire heparanome and the nature of the interactions among these domains and their protein ligands. Structural elucidation of heparan sulfate and heparin oligosaccharides is a major obstacle in advancing structure–function relationships and heparanomics. There are several factors that exacerbate the challenges involved in the structural elucidation of heparin and heparan sulfate; therefore, there is great interest in developing novel strategies and analytical tools to overcome the barriers in decoding the enigmatic heparanome. This review focuses on the applications of isotopes, both radioisotopes and stable isotopes, in the structural elucidation of the complex heparanome at the disaccharide or oligosaccharide level using liquid chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry. This review also outlines the utility of isotopes in determining the substrate specificity of biosynthetic enzymes that eventually dictate the emergence of biologically active oligosaccharides.     

Synthesis and Optical and Electrochemical Studies on Dicationic Fluorenophanes

The synthesis of 2,7-bridged dicationic fluorenophanes consisting of benzimidazole, imidazole, and benzotriazole units and their absorption, photoluminescence, and electrochemical behavior are described.     

Syntheses and catalytic activities of Pd(II) dicarbene and hetero-dicarbene complexes

A series of palladium(II) complexes (1-6) bearing cis-chelating homo-dicarbene ligands with varying alkyl bridges (C1-C3) and N-heterocyclic backbones (imidazole and benzimidazole) have been synthesized by reaction of Pd(OAc)₂ with the respective diazolium bromides (A·2HBr - F·2HBr) in DMSO. A comparative catalytic study employing aryl chlorides in the Mizoroki-Heck reaction revealed the superiority of methylene- and propylene-bridged dibenzimidazolin-2-ylidenes over their imidazole-derived analogues. Based on these results, two new propylene-bridged hetero-dicarbene complexes (7 and 8) were designed containing a mixed benzimidazole/imidazole-derived NHC-donor set. Notably, both complexes outperformed their homo-dicarbene analogues, which may be due to the electronic asymmetry induced by hetero-dicarbene ligands. The molecular structures of complex 6 and 8 are also presented.     

Determination of thermoluminescence kinetic parameters of thulium doped lithium calcium borate

For the first time kinetic parameters of thulium doped Lithium calcium borate (LCB) Thermoluminescence (TL) material are reported here. Irradiated LCB:Tm³⁺ powder has revealed two intense TL glow peaks one at 510 (peak 1) and the other at 660 K (peak 2). Activation energy (E), frequency factor (s) and order of kinetics (b) of these peaks were determined by various heating rate (VHR), initial rise (IR), and peak shape (PS) methods. The trap depth and frequency factor determined for peaks 1 and 2 of LCB:Tm phosphor using VHR and IR methods are in good agreement. The average activation energy of peaks 1 and 2 obtained by these methods is 1.62 and 1.91 eV respectively. The frequency factors of peaks 1 and 2 are in the range of 10^13–16 and 10^12–14 sec⁻¹ respectively. The E and s values estimated using the glow peak shape dependent parameters are relatively less compared to the values obtained from other methods. The large difference in these values is due to the complex nature of the glow curves. The order of the kinetics process for complex glow curve peaks could not be assigned on the basis of shape parameters alone but T_m response on absorbed dose is to be considered for final confirmation. Glow peaks 1 and 2 of LCB:Tm³⁺ obey first and general order kinetics respectively.     

Growth and characterization of an organic NLO material ammonium malate

Second harmonic generation organic material, ammonium malate (AM), has been synthesized and grown as quality single crystals by the slow evaporation technique. As-grown crystals were characterized by X-ray powder diffraction (XRPD) and Fourier transforms – nuclear magnetic resonance (FT-NMR). The optical band gap was estimated for AM crystal using UV–vis study. Measuring transmittance of AM permitted the calculation of the refractive index n; the extinction coefficient K and both the real ε_r and imaginary ε_i components of the dielectric permittivity as functions of photon energy. Density functional theory at the HF/3-21 G (d, p) level has been used to calculate the first-order hyperpolarizability of AM. The second harmonic conversion efficiency of AM was determined using Kurtz powder technique; it was observed to be greater than that of KDP. The mechanical anisotropy property of the grown crystals was studied using Vickers microhardness tester at different planes. The photoluminescence study is also analyzed. The growth features were analyzed by wet chemical etching studies. The factor group analysis was carried out for AM which predicts that there are 132 vibrational optical modes.     

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis,DNA/Protein Binding and In Vitro Cytotoxicity Studies

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tp^py) ligand (1–3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [Tp^pyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in Tp^pyZn(II) chemistry. In complex [Tp^pyZn(H₂O)][BF₄] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [Tp^pyZnN₃] (3). The complexes (1–3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 10⁴–10⁵ M⁻¹. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1–3) exhibited good IC₅₀ values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.     

Structural,Morphological and Electrical Studies on Barium Strontium Titanate Thin Films Prepared by Sol‐Gel Technique

The crystal structure, surface morphology, compositional homogeneity and electrical properties of barium strontium titanate (BST) thin films are investigated. The films were deposited on bare silicon and platinum coated silicon substrates by spin coating process. The precursor solution with Ba/Sr ratio 70/30 was prepared by sol‐gel synthesis using metal alkoxides. The crystalline nature and morphology of the films are found to be strongly influenced by the heating cycle adopted to form the Ba_0.7Sr_0.3TiO₃ layer. The elemental composition analysis on the surface and in‐depth confirms the stoichiometry of the films. The dielectric constant at 100 kHz and dissipation factor at room temperature is found to be 120 and 0.0236 for the films with 400nm thickness annealed at 700°C for 2 hrs. The leakage current density of the film is found to be 4x10^‐8 A/cm² from I‐V measurements.     

Synthesis and Characterization of the Ethylene-Carbonate-Linked L-Valine Derivatives of 4,4-Dimethylcurcumin with Potential Anticancer Activities

Natural phenolic products from herbal medicines and dietary plants constitute the main source of lead compounds for the development of the new drug. 4,4-Dimethylcurcumin (DMCU) is a synthetic curcumin derivative and exhibits anticancer activities against breast, colon, lung, and liver cancers. However, further development of DMCU is limited by unfavorable compound properties such as very low aqueous solubility and moderate stability. To increase its solubility, we installed either or both of the ethylene-carbonate-linked L-valine side chains to DMCU phenolic groups and produced targeted 1-trifluoroacetic acid (1-TFA) and 2-trifluoroacetic acid (2-TFA) derivatives. The terminus L-valine of ethylene-carbonate-linked side chain is known to be a L-type amino acid transporter 1 (LAT1) recognition element and therefore, these two derivatives were expected to readily enter into LAT1-expressing cancer cells. In practice, 1-TFA or 2-TFA were synthesized from DMCU in four steps with 34–48% overall yield. Based on the corresponding LC-MS analysis, water solubility of DMCU, 1-TFA, and 2-TFA at room temperature (25 ± 1 °C) were 0.018, 249.7, and 375.8 mg/mL, respectively, indicating >10,000-fold higher solubility of 1-TFA and 2-TFA than DMCU. Importantly, anti-proliferative assay demonstrated that 2-TFA is a potent anti-cancer agent against LAT1-expressing lung cancer cells NCI-H460, NCI-H358, and A549 cells due to its high intracellular uptake compared to DMCU and 1-TFA. In this study, we logically designed and synthesized the targeted compounds, established the LC-MS analytical methods for evaluations of drug solubility and intracellular uptake levels, and showed improved solubility and anti-cancer activities of 2-TFA. Our results provide a strategical direction for the future development of curcuminoid-like phenolic compounds.     

Investigations on the Nucleation Kinetics of L-Arginine Phosphate single crystals

The nucleation parameters, such as radius of the critical nucleus and critical free energy change have been evaluated for LAP single crystals. The interfacial tension determined by conducting the induction period measurements has been used for the evaluation of nucleation parameters. The determined interfacial tension is found to be comparable with theoretical literature values.