Synthesis, characterization and antifungal evaluation of 5-substituted-4-amino-1,2,4-triazole-3-thioesters

A series of 5-substituted-4-amino-1,2,4-triazole-3-thioesters was synthesized by converting variously substituted organic acids successively into the corresponding esters, hydrazides, 5-substituted-1,3,4-oxadiazole-2-thiols, 5-substituted-1,2,4-triazole-2-thiols and 5-substituted-1,3,4-oxadiazole-2-thioesters. Finally the target compounds were obtained by refluxing 5-substituted-1,3,4-oxadiazole-2-thioesters in the presence of hydrazine hydrate and absolute alcohol. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.     

Inf–sup conditions for twofold saddle point problems

Necessary and sufficient conditions for existence and uniqueness of solutions are developed for twofold saddle point problems which arise in mixed formulations of problems in continuum mechanics. This work extends the classical saddle point theory to accommodate nonlinear constitutive relations and the twofold saddle structure. Application to problems in incompressible fluid mechanics employing symmetric tensor finite elements for the stress approximation is presented.     

Products formed at intermediate stages of electrochemical perfluorination of propionyl and n-butyryl chlorides. Further evidence in support of NiF3 mediated free radical pathway

The partially fluorinated HF soluble intermediates formed during the electrochemical perfluorination of propionyl chloride (PC) and n-butyryl chloride (n-BC) were analyzed after passing 0%, 25%, 50%, 75% and 100% of theoretical charge required for the fluorination of PC and n-BC. The acid fluorides formed were converted to their corresponding sodium salt by alkali treatment and were separated by methanol extraction. The methanol was subsequently removed from the extract by vacuum distillation and the residue containing partially fluorinated sodium carboxylates was analyzed using ¹⁹F and ¹H NMR spectra. Initial perfluorination on activated electrode surface indicates the operation of ‘zipper-mechanism’. Formation of partially fluorinated product mixture, initial selectivity towards primary and secondary carbon, carbon chain isomerization and formation of cleaved and coupled products support the general operation of free radical pathway in the overall electrochemical process.     

A semi-analytical description of protein folding that incorporates detailed geometrical information

Much has been done to study the interplay between geometric and energetic effects on the protein folding energy landscape. Numerical techniques such as molecular dynamics simulations are able to maintain a precise geometrical representation of the protein. Analytical approaches, however, often focus on the energetic aspects of folding, including geometrical information only in an average way. Here, we investigate a semi-analytical expression of folding that explicitly includes geometrical effects. We consider a Hamiltonian corresponding to a Gaussian filament with structure-based interactions. The model captures local features of protein folding often averaged over by mean-field theories, for example, loop contact formation and excluded volume. We explore the thermodynamics and folding mechanisms of beta-hairpin and alpha-helical structures as functions of temperature and Q, the fraction of native contacts formed. Excluded volume is shown to be an important component of a protein Hamiltonian, since it both dominates the cooperativity of the folding transition and alters folding mechanisms. Understanding geometrical effects in analytical formulae will help illuminate the consequences of the approximations required for the study of larger proteins.     

Interference-induced electron- and hole-conduction asymmetry

Principles established by Shephard and Paddon-Row for optimizing and controlling intramolecular electron transport through the modulation of interfering pathways are employed to design new molecules for steady-state conduction experiments aimed at manifesting electron?Chole conduction asymmetry in a unique way. First, a review of the basic principles is presented through application to a pertinent model system in which a molecule containing donor and acceptor terminal linking groups with an internal multiple-pathway bridge is used to span two metal electrodes. Different interference patterns are produced depending on whether the through-molecule coupling pathways are symmetric or antisymmetric with respect to a topological bisecting plane, giving rise to asymmetric electron and hole conductances at the tight-binding (Hückel) level; this process is also described from a complementary molecular-orbital viewpoint. Subsequently, a new molecular system based on organic polyradicals is designed to allow such asymmetry to be realized in single-molecule conduction experiments. These polyradicals are analyzed using analogous simple models, density-functional theory (DFT) calculations of steady-state transmission, and intermediate neglect of differential overlap (INDO) calculations of intramolecular connectivity, verifying that polyradicals at low temperatures should show experimentally measureable electron?Chole conduction asymmetry. A key feature of this system is that the polyradicals form a narrow partially occupied band of orbitals that lie within and well separated from the HOMO and LUMO orbitals of the surrounding molecular scaffold, allowing for holes and electrons to be transported through the same molecular band.     

Microscale prediction of deformation in an austenitic stainless steel under uniaxial loading

In this study, the deformation behaviour of polycrystalline austenitic 316H stainless steel under uniaxial loading is investigated by means of in-situ neutron diffraction (ND) measurement and crystal plasticity-based finite element (FE) modelling. Data have been obtained for the macroscopic stress–strain response and the lattice strain evolution in the longitudinal and transverse direction relative to the uniaxial loading axis. Comparison between the model predictions and the ND measurements suggests that in most cases the FE model can predict the lattice strain evolution at the microscale and capture the general trends observed in the experiments. Both ND measurements and FE modelling simulations identify little effect of micromorphology effect on the longitudinal lattice strain evolution, while the transverse lattice strain response appears to be sensitive to the microstructure, in particular the initial crystallographic orientation of the material.     

Modulation theory solution for nonlinearly resonant,fifth‐order Korteweg–de Vries,nonclassical, traveling dispersive shock waves

A new class of resonant dispersive shock waves was recently identified as solutions of the Kawahara equation— a Korteweg–de Vries (KdV) type nonlinear wave equation with third‐ and fifth‐order spatial derivatives— in the regime of nonconvex, linear dispersion. Linear resonance resulting from the third‐ and fifth‐order terms in the Kawahara equation was identified as the key ingredient for nonclassical dispersive shock wave solutions. Here, nonlinear wave (Whitham) modulation theory is used to construct approximate nonclassical traveling dispersive shock wave (TDSW) solutions of the fifth‐ order KdV equation without the third derivative term, hence without any linear resonance. A self‐similar, simple wave modulation solution of the fifth order, weakly nonlinear KdV–Whitham equations is obtained that matches a constant to a heteroclinic traveling wave via a partial dispersive shock wave so that the TDSW is interpreted as a nonlinear resonance. The modulation solution is compared with full numerical solutions, exhibiting excellent agreement. The TDSW is shown to be modulationally stable in the presence of sufficiently small third‐order dispersion. The Kawahara–Whitham modulation equations transition from hyperbolic to elliptic type for sufficiently large third‐order dispersion, which provides a possible route for the TDSW to exhibit modulational instability.     

Intracellular pH mapping with SNARF-1 and confocal microscopy. I: A quantitative technique for living tissue and isolated cells

A fluorescent pH indicator in conjunction with confocal microscopy, was used to map intracellular pH in a variety of cells and tissues with high spatial resolution. The new pH-sensitive fluorescent probe SNARF-1 was excited with the 488 nm band of the argon ion laser of a Bio-Rad MRC-500 confocal microscope. Ratio images were created with pixel-by-pixel division, with the intensity of these images representing a function of pH, that is independent of dye concentration, photobleaching or path length. Cell cultures of rat aortic smooth muscle were loaded with 20 μм SNARF-1/AM for 20 min at 37°C. Intracellular pH levels were calibrated in situ by treatment of each cell with nigericin (20 μм) in solutions of known pH. The cytosolic pH of the majority of cells was uniform, however, pH gradients were evident between the cytosol and nuclear regions, indicating the ability of this technique to map intracellular and intraorganelle pH. Rat C6 glioblastoma spheroids were cultured then loaded with SNARF-1/AM at 10°C for 90 min. The pH values were calibrated in vitro, using SNARF-1 acid in buffered solutions of known pH. Ratio images of the bisected spheroids showed a marked gradient in pH from the outer cells compared with central necrotic cells. The degree of involvement of acidification in muscle fatigue was investigated by simultaneously determining force generation and intracellular pH in individual fibres of an intact rat muscle. The investigation was performed during a stimulation protocol which induced significant fatigue in the force response of the muscle. The fatigue protocol induced little change in cytosolic pH in the fibres. We show that the use of SNARF-1, in conjunction with confocal microscopy is a powerful technique for accurately mapping pH within single cells, multicellular tissues and intact organs, as well as for accurately recording dynamic changes in pH.     

Self-assembled monolayers for liquid crystal alignment: simple preparation on glass using alkyltrialkoxysilanes

A simple procedure for the preparation of octadecylsiloxane self-assembled monolayers (SAMs) on float glass substrates is described. The method utilizes commercial octadecyltriethoxysilane, OTE: n-C₁₈H₃₇Si(OCH₂CH₃)₃, as the SAM precursor, with deposition accomplished in toluene solution using n-butylamine as catalyst. This synthetic approach obviates the use of the problematic trichlorosilanes typically required for the preparation of high quality SAMs, and is characterized by a wide 'process window,' utilizing off-the-shelf reagents without special handling.