Synthesis and Biophysical Studies on 35‐Deoxy Amphotericin B Methyl Ester

The use of molecular editing in the elucidation of the mechanism of action of amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its designed analogues is developed, which relies on an efficient gram‐scale synthesis of various subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone was identified. The implementation of the approach has enabled the preparation of 35‐deoxy amphotericin B methyl ester. Investigation of the antifungal activity and efflux‐inducing ability of this amphotericin B congener provided new clues to the role of the 35‐hydroxy group and is consistent with the involvement of double barrel ion channels in causing electrolyte efflux.     

Filamin cross-linked semiflexible networks: fragility under strain

The semiflexible F-actin network of the cytoskeleton is cross-linked by a variety of proteins including filamin, which contains Ig domains that unfold under applied tension. We examine a simple filament network model cross-linked by such unfolding linkers that captures the main mechanical features of F-actin networks cross-linked by filamin proteins and show that, under sufficient strain, the network spontaneously self-organizes so that an appreciable fraction of the filamin cross-linkers are at the threshold of domain unfolding. We propose and test a mean-field model to account for this effect. We also suggest a qualitative experimental signature of this type of network reorganization under applied strain that may be observable in intracellular microrheology experiments of Crocker et al.     

Scaling of fluctuations in traffic on complex networks

We study the scaling of fluctuations with the mean of traffic in complex networks using a model where the arrival and departure of "packets" follow exponential distributions, and the processing capability of nodes is either unlimited or finite. The model presents a wide variety of exponents between 1/2 and 1 for this scaling, revealing their dependence on the few parameters considered, and questioning the existence of universality classes. We also report the experimental scaling of the fluctuations in the Internet for the Abilene backbone network. We found scaling exponents between 0.71 and 0.86 that do not fit with the exponent 1/2 reported in the literature.     

Hypothermic renal preservation with a sucrose/ polyethylene glycol solution in a rabbit renal transplant model

Renal preservation at for 24 hours at hypothermia was studied in a rabbit model after flush cooling with sucrose-based solution (SBS), compared with a standard preservation solution (in this case, Marshall's Hypertonic Citrate solution - HCA). Polyethylene glycol supplementation to SBS (SBS-PEG) was also investigated. Renal function was measured by plasma creatinine assays during 1 months post transplantation, and pathology of the explanted kidneys was undertaken. Results showed that survival at 28 days was similar in all groups, (HCA - 3 out of 6; SBS - 2 out of 5; SBS-PEG - 3 out of 5), and there were no differences in recovery of plasma creatinine values. Histopathological evaluation of the grafts indicated that SBS preservation resulted in more severe damage after transplantation (P less than 0.05 in both corticomedullary region and medulla compared to HCA), whilst addition of PEG reduced the damage score to that seen with HCA. SBS can be used as a simple, inexpensive preservation solution for kidney cold storage provided that PEG is used as an additional colloid.     

A simple proof that third-order quadrupole perturbations of the NMR central transition of half-integral spin nuclei are zero

It has been known for a long time that the third-order quadrupole corrections to transitions from mz=-n/2 to mz=+n/2 are zero in the NMR of half-integer nuclei. However, the derivation has relied on deriving the corrections to the energy levels through somewhat laborious calculations. Only when the transitions between the levels were calculated was it revealed that the corrections to the transition frequency were zero. In this paper, we use Liouville-space methods to work with the transitions directly. Application of a recently published [A.D. Bain, Exact calculation, using angular momentum, of combined Zeeman and quadrupolar interactions in NMR, Mol. Phys. 101 (2003) 3163-3175] selection rule for the quadrupole coupling leads to a very simple proof that third-order corrections to the central and other symmetrical transitions are zero. The simplicity of the proof suggests there is a fundamental symmetry involved.     

Rapid method for simultaneous determination of ascorbic acid and zinc in effervescent tablets by capillary zone electrophoresis with contactless conductivity detection

Ascorbic acid and zinc are essential nutrients that play important roles in nutrition, immune support, and maintenance of health. For this reason, both compounds are widely used as ingredients in dietary supplements. We report, for the first time, an analytical method for fast simultaneous determination of ascorbic acid and zinc. A single analysis run is possible every 80 s (45 injections/h). The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection using a fused silica capillary with 50 cm length (effective length of 10 cm). The separation was achieved by using a background electrolyte composed by 30 mmol/L of 2‐(morpholin‐4‐yl)ethane‐1‐sulfonic acid and 30 mmol/L of histidine, pH 6.1. The detection limits were 10 and 20 μmol/L and recovery values for spiked samples were 101 and 100% for zinc and ascorbic acid, respectively. The results obtained with the developed procedure were compared to those obtained by titration (ascorbic acid) and flame atomic absorption spectroscopy (zinc), and no statistically significant differences were observed (95% confidence level).     

Nano‐Ferroelectric for High Efficiency Overall Water Splitting under Ultrasonic Vibration

Piezocatalysis, converting mechanical vibration into chemical energy, has emerged as a promising candidate for water‐splitting technology. However, the efficiency of the hydrogen production is quite limited. We herein report well‐defined 10 nm BaTiO₃ nanoparticles (NPs) characterized by a large electro‐mechanical coefficient which induces a high piezoelectric effect. Atomic‐resolution high angle annular dark field scanning transmission electron microscopy (HAADF‐STEM) and scanning probe microscopy (SPM) suggests that piezoelectric BaTiO₃ NPs display a coexistence of multiple phases with low energy barriers and polarization anisotropy which results in a high electro‐mechanical coefficient. Landau free energy modeling also confirms that the greatly reduced polarization anisotropy facilitates polarization rotation. Employing the high piezoelectric properties of BaTiO₃ NPs, we demonstrate an overall water‐splitting process with the highest hydrogen production efficiency hitherto reported, with a H₂ production rate of 655 μmol g^?1 h^?1, which could rival excellent photocatalysis system. This study highlights the potential of piezoelectric catalysis for overall water splitting.     

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Acidic 4‐hydroxy‐1,2,3‐triazole is a proven bioisostere of acidic functions that has recently been used to replace the acidic moieties of biologically active leads. Straightforward chemical strategies for the synthesis of the three possible N‐alkylated 4‐hydroxy‐1,2,3‐triazole regioisomers have been designed and reported herein, by identifying the optimal conditions under which the alkylation of ethyl 4‐benzyloxy‐1,2,3‐triazolecarboxylate (compound 19 ) can be regiodirected to the triazole N(b) position and thus produce the only isomer that cannot be obtained via the cycloaddition reaction. Furthermore, an innovative platform for parallel synthesis, called Arachno and which has been patented by the authors' group, has been used to speed up the process, and an NMR study has been carried out to better understand the reactivity of compound 19 towards the N(b) position. A library of benzyloxy protected 4‐hydroxy‐1,2,3‐triazoles has been prepared using the two strategies: regiodirection for the N(b) and N(c) isomers and cycloaddition for the N(a) isomers; the processes are described herein. The three N‐alkylated regioisomer series have been characterized spectroscopically (NMR and MS). The subsequent catalytic hydrogenation of the 4‐benzyloxy protective group on the N‐alkylated‐4‐benzyloxy‐5‐ethoxycarbonyl‐1,2,3‐triazoles provided the corresponding substituted 4‐hydroxy‐1,2,3‐triazoles.