Efficient synthesis of [1,2,3]triazolo[5,1-c][1,4]benzoxazines through palladium-copper catalysis

A wide variety of [1,2,3]triazolo[5,1-c][1,4]benzoxazines were synthesized through palladium-copper catalyzed reactions of 1-azido-2-(prop-2-ynyloxy)benzene with aryl/vinyl iodides. A plausible reaction mechanism has also been proposed.     

Gut microbiota, diet, and heart disease

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.     

Could diastereoselectivity in the presence of O-2 chiral nonparticipating groups be an indicator of glycopyranosyl oxacarbenium ions in glycosylation reactions?

Although long postulated, the existence of glycopyranosyl oxacarbenium ions as intermediates or transition states (TS) in chemical glycosylation reactions has not been convincingly demonstrated experimentally. It is anticipated that elucidation of such reactive species will greatly assist synthetic chemists to control the α/β stereoselectivity by rational means. Previous density functional theory (DFT) calculations from our group found that the torsion potential about C-2-O-2 in protected glycopyranosyl donors changed from a conventional 3-fold rotor to a 2-fold rotor with a strong syn (CH-2-C-2-O-2-CPg) preference once the donor was ionized to its oxacarbenium ion. This suggested to us that if CPg of the protecting group was a chiral carbon, then diastereoselectivity might be observed in glycosylation reactions that proceed through oxacarbenium ions. The hypothesis to test is as follows: if a nonparticipating O-2 racemic chiral protecting group exhibits diastereoselectivity in glycosylation reactions, then the reaction probably proceeds through an oxacarbenium ion intermediate or TS. We present data for O-2 ether-protected d-glucopyranosyl donors where the racemic protecting group 1-methyl 1'-methylcyclopropylmethyl (MCPM) provides the chirality. MCPM proves to be more activating than the O-2-benzyl ether, and in cases where the donor is otherwise deactivated, several examples of moderate diastereoselectivity are found. These results can be interpreted to indicate that a continuum of reactivity exists where some glycosyl donors form oxacarbenium ions in glycosylation reactions but more reactive donors do not. The strongly activating properties of the cyclopropylmethyl ether functionality and the ability to induce diastereoselectivity with chiral derivatives strongly suggest widespread applications.     

Synergic effect of multi-walled carbon nanotubes and gold nanoparticles towards immunosensing of ricin with carbon nanotube-gold nanoparticles-chitosan modified screen printed electrode

An amperometric immunosensor for the specific detection of Ricinus communis is reported. Screen printed electrodes (SPEs) were modified with gold nanoparticles (GNPs) loaded multiwalled carbon nanotubes (MWCNTs)-chitosan (Ch) film. The ratio of MWCNT and GNP was optimised to get best electrochemically active electrode. Sandwich immunoassay format was used for the immunosensing of ricin. The revealing antibodies tagged with the enzyme alkaline phosphatase (ALP) converts the substrate 1-naphthyl phosphate into 1-naphthol that was determined with the amperometric technique. The amperometric current obtained was correlated with the concentration of ricin. The prepared GNP-MWCNT-Ch-SPE showed high stability due to the Ch film, short response time with good reproducibility and increased shelf life of the electrodes immobilised with antibodies. The electrochemical activity of the electrode improved because of optimization of composition of CNTs and gold nanoparticles. Under the optimal conditions, the modified electrode showed a wide linear response to the concentration of ricin in the range of 2.5-25 ng mL(-1) with a limit of detection of 2.1 ng mL(-1) and with a relative standard deviation of 5.1% and storage life of 32 days.     

Gold nano particles catalyzed oxidation of hydrazine by a metallo-superoxide complex: experimental evidences for surface activity of gold nano particles

Gelatin-capped gold nano particles (GNPs) of diameter 23, 28 and 36 nm were prepared and characterized as almost monodispersed, near-spherical solids. In acidic media, these GNPs at their very low concentration level (～10(-13) M) catalyze the oxidation of hydrazine by the metallo-superoxide, [(NH(3))(4)Co(III)(μ-NH(2),μ-O(2))Co(III)(NH(3))(4)](NO(3))(4) (1). In the presence of a large excess of hydrazine over [1], the catalyzed oxidation is first-order in [1], [GNPs] and media alkalinity. The pure first-order dependence implies that the size as well as the nature of the catalyst remained unchanged during the reaction. The catalytic efficacies increased with increased total surface area of the GNPs. Increasing T(Hydrazine) (T(Hydrazine) is the analytical concentration of hydrazine) tends to saturate the first-order rate constant (k(o)) for hydrazine oxidation and a plot of 1/k(o)versus T(Hydrazine) was found to be linear at a particular [GNPs], indicating the GNPs assisted deprotonation of N(2)H(5)(+) to N(2)H(4). The rate constants show a non-linear behavior with temperature studied in the range 288-308 K. At a lower temperature interval, viz. 288-298 K, k(o) increases with increasing temperature whereas at temperature interval, viz. 303-308 K, k(o) decreases with temperature. Such a variation indicates the important process of absorption and desorption of the reactants on and from the surface. A plausible mechanism for the GNPs catalyzed oxidation of hydrazine is suggested.     

Fluoranthene based fluorescent chemosensors for detection of explosive nitroaromatics

A novel fluoranthene based fluorescent chemosensor for the detection of picric acid (PA) at the parts per billion (ppb) level was evaluated. Static fluorescence quenching was the dominant process by intercalative π-π interaction between fluoranthene (S(1)) and nitroaromatics.     

Imino-phenolic-pyridyl conjugates of calix[4]arene (L1 and L2) as primary fluorescence switch-on sensors for Zn2+ in solution and in HeLa cells and the recognition of pyrophosphate and ATP by [ZnL2

Pyridyl-based triazole-linked calix[4]arene conjugates, viz. L(1) and L(2), were synthesized and characterized. These two conjugates were shown to be selective and sensitive for Zn(2+) among the 12 metal ions studied in HEPES buffer medium by fluorescence, absorption, and visual color change with the detection limit of ~31 and ~112 ppb, respectively, by L(1) and L(2). Moreover, the utility of the conjugates L(1) and L(2) in showing the zinc recognition in live cells has also been demonstrated using HeLa cells as monitored by fluorescence imaging. The zinc complexes of L(1) and L(2) were isolated, and the structure of [ZnL(1)] has been established by single-crystal XRD and that of [ZnL(2)] by DFT calculations. TDDFT calculations were performed in order to demonstrate the electronic properties of receptors and their zinc complexes. The isolated zinc complexes, viz. [ZnL(1)] and [ZnL(2)], have been used as molecular tools for the recognition of anions on the basis of their binding affinities toward Zn(2+). [ZnL(2)] was found to be sensitive and selective toward phosphate-bearing ions and molecules and in particular to pyrophosphate (PPi) and ATP among the other 18 anions studied; however, [ZnL(1)] was not sensitive toward any of the anions studied. The selectivity has been shown on the basis of the changes observed in the emission and absorption spectral studies through the removal of Zn(2+) from [ZnL(2)] by PPi. Thus, [ZnL(2)] has been shown to detect PPi up to 278 ± 10 ppb at pH 7.4 in aqueous methanolic (1/2 v/v) HEPES buffer.     

A novel method to fabricate patterned bilayer lipid membranes

We introduce a new method for forming tethered bilayer lipid membranes on surfaces patterned using a photocleavable self-assembled monolayer (SAM). A SAM terminated with a hydrophobic fluorocarbon residue was bound to a gold surface through a link containing a photocleavable ortho-nitrobenzyl moiety. Hydrophilic regions were produced by irradiation with soft UV (365 nm) through a photomask. The patterned surface was characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Tethered bilayer lipid membranes with well-defined bilayer and monolayer regions were then formed by exposure to egg PC vesicles. The membranes had resistance and capacitance values of 0.52 MOmega.cm2 and 0.83 microF.cm-2, respectively.     

Dynamic properties of water around a protein-DNA complex from molecular dynamics simulations

Formation of protein-DNA complex is an important step in regulation of genes in living organisms. One important issue in this problem is the role played by water in mediating the protein-DNA interactions. In this work, we have carried out atomistic molecular dynamics simulations to explore the heterogeneous dynamics of water molecules present in different regions around a complex formed between the DNA binding domain of human TRF1 protein and a telomeric DNA. It is demonstrated that such heterogeneous water motions around the complex are correlated with the relaxation time scales of hydrogen bonds formed by those water molecules with the protein and DNA. The calculations reveal the existence of a fraction of extraordinarily restricted water molecules forming a highly rigid thin layer in between the binding motifs of the protein and DNA. It is further proved that higher rigidity of water layers around the complex originates from more frequent reformations of broken water-water hydrogen bonds. Importantly, it is found that the formation of the complex affects the transverse and longitudinal degrees of freedom of surrounding water molecules in a nonuniform manner.     

Density functional studies on dinuclear {Ni(II)Gd(III)} and trinuclear {Ni(II)Gd(III)Ni(II)} complexes: magnetic exchange and magneto-structural maps

Theoretical calculations using density functional methods have been performed on two dinuclear {Ni(II)-Gd(III)} and two trinuclear {Ni(II)-Gd(III)-Ni(II)} complexes having two and three μ-OR (R = alkyl or aromatic groups) bridging groups. The different magnetic behaviour, having moderately strong ferromagnetic coupling for complexes having two μ-OR groups and weak ferromagnetic coupling for complexes having three μ-OR groups, observed experimentally is very well reproduced by the calculations. Additionally, computation of overlap integrals MO and NBO analysis reveals a clear increase in antiferromagnetic contribution to the net exchange for three μ-OR bridged {Ni-Gd} dimers and also provides several important clues regarding the mechanism of magnetic coupling. Besides, MO and NBO analysis discloses the role of the empty 5d orbitals of the Gd(III) ion on the mechanism of magnetic coupling. Magneto-structural correlations for Ni-O-Gd bond angles, Ni-O and Gd-O bond distances, and the Ni-O-Gd-O dihedral angle have been developed and compared with the published experimental {Ni-Gd} structures and their J values indicate that the Ni-O-Gd bond angles play a prominent role in these types of complexes. The computation has then been extended to two trinuclear {Ni(II)-Gd(III)-Ni(II)} complexes and here both the {Ni-Gd} and the {Ni-Ni} interactions have been computed. Our calculations reveal that, for both structures studied, the two {NiGd} interactions are ferromagnetic and are similar in strength. The {Ni-Ni} interaction is antiferromagnetic in nature and our study reveals that its inclusion in fitting the magnetic data is necessary to obtain a reliable set of spin Hamiltonian parameters. Extensive magneto-structural correlations have been developed for the trinuclear complexes and the observed J trend for the trinuclear complex is similar to that of the dinuclear {Ni-Gd} complex. In addition to the structural parameters discussed above, for trinuclear complexes the twist angle between the two Ni-O-Gd planes is also an important parameter which influences the J values.