Could chroman-4-one derivative be a better inhibitor of PTR1? – Reason for the identified disparity in its inhibitory potency in Trypanosoma brucei and Leishmania major

Most notable Kinetoplastids are of the genus Trypanosoma and Leishmania, affecting several millions of humans in Africa and Latin America. Current therapeutic options are limited by several drawbacks, hence the need to develop more efficacious inhibitors. An investigation to decipher the mechanism behind greater inhibitory potency of a chroman-4-one derivative (compound 1) in Trypanosoma brucei pteridine reductase 1 (TbPTR1) and Leishmania major pteridine reductase 1 (LmPTR1) was performed. Estimation of ΔG_bind revealed that compound 1 had a greater binding affinity in TbPTR1 with a ΔG_bind value of −49.0507 Kcal/mol than −29.2292 Kcal/mol in LmPTR1. The ΔGbind in TbPTR1 were predominantly contributed by “strong” electrostatic energy compared to the “weak” van der Waals in LmPTR1. In addition to this, the NADPH cofactor contributed significantly to the total energy of TbPTR1. A characteristic weak aromatic π interaction common in PTR1 was more prominent in TbPTR1 than LmPTR1. The consistent occurrence of high-affinity conventional hydrogen bond interactions as well as a steady interaction of crucial active site residues like Arg14/Arg17, Ser95/Ser111, Phe97/Phe113 in TbPTR1/LmPTR1 with chroman-4-one moiety equally revealed the important role the moiety played in the activity of compound 1. Overall, the structural and conformational analysis of the active site residues in TbPTR1 revealed them to be more rigid than LmPTR1. This could be the mechanism of interaction TbPTR1 employs in exerting a greater potency than LmPTR1. These findings will further give insight that will be assistive in modifying compound 1 for better potency and the design of novel inhibitors of PTR1.     

Fracture behavior and mechanical,thermal, and rheological properties of biodegradable films extruded by flat die and calender

The development of biodegradable materials for tailored applications, particularly in the field of polymeric films and sheets, is a challenging technological goal as well as a contribution to help protect the environment. Poly(lactic) acid (PLA) is a promising substitute for several oil-based polymers; however, to overcome its thermal and mechanical drawbacks, researchers have developed solutions such as blending PLA with polybutylene adipate terephthalate (PBAT), which is capable of increasing the ductility of the final material. In this study, PLA/PBAT binary blends, with minimum possible content of nonrenewable materials, were examined from processing, thermal, morphological, and rheological perspective. An optimized PLA/PBAT ratio was chosen as the polymeric basis to obtain a biodegradable formulation by adding a biobased plasticizer and appropriate fillers to produce a micrometer film with tailored flexibility and tear resistance. The processing technology involved flat-die extrusion, followed by calendering. The tearing resistance of the produced film was investigated, and the results were compared with literature data. A study on the essential work of fracture was implemented to explore the mode III out-of-plane fracture resistance starting from a trouser tear test.     

Change of evaporation rate of single monocomponent droplet with temperature using time-resolved phase rainbow refractometry

Droplet evaporation characterization, although of great significance, is still challenging. The recently developed phase rainbow refractometry (PRR) is proposed as an approach to measuring the droplet temperature, size as well as evaporation rate simultaneously, and is applied to a single flowing n-heptane droplet produced by a droplet-on-demand generator. The changes of droplet temperature and evaporation rate after a transient spark heating are reflected in the time-resolved PRR image. Results show that droplet evaporation rate increases with temperature, from ?1.28$\times {10}^{?8}$ m²/s at atmospheric 293 K to a range of (?1.5, ?8)$\times {10}^{?8}$ m²/s when heated to (294, 315) K, agreeing well with the Maxwell and Stefan–Fuchs model predictions. Uncertainty analysis suggests that the main source is the indeterminate gradient inside droplet, resulting in an underestimation of droplet temperature and evaporation rate. With the demonstration on simultaneous measurements of droplet refractive index as well as droplet transient and local evaporation rate in this work, PRR is a promising tool to investigate single droplet evaporation in real engine conditions.     

A model for crack formation during active solid pyrolysis of a char-forming solid: crack patterns; surface area generation; volatile mass efflux

A model is developed for the formation and propagation of cracks in a material sample that is heated at its top surface, pyrolyses, and then thermally degrades to form char. In this work the sample is heated uniformly over its entire top surface by a hypothetical flame (a heat source). The pyrolysis mechanism is described by a one-step overall reaction that is dependent nonlinearly on the temperature (Arrhenius form). Stresses develop in response to the thermal degradation of the material by means of a shrinkage strain caused by local mass loss during pyrolysis. When the principal stress exceeds a prescribed threshold value, the material forms a local crack. Cracks are found to generally originate at the surface in response to heating, but occasionally they form in the bulk, away from ever-changing material boundaries. The resulting cracks evolve and form patterns whose characteristics are described. Quantities examined in detail are: the crack spacing in the pyrolysis zone; the crack length evolution; the formation and nature of crack loops which are defined as individual cracks that have joined to form loops that are disconnected from the remaining material; the formation of enhanced pyrolysis area; and the impact of all of the former quantities on mass flux. It is determined that the mass flux from the sample can be greatly enhanced over its nominal (non-cracking) counterpart. The mass efflux profile qualitatively resembles those observed in Cone Calorimeter tests.     

Experimental and Theoretical Mechanistic Study on the Thermal Decomposition of 3,3-diphenyl-4-(trichloromethyl)-5-nitropyrazoline

The present paper is a continuation of comprehensive study regarding to synthesis and properties of pyrazoles and their derivatives. In its framework an experimental and theoretical studies of thermal decomposition of the 3,3-diphenyl-4-(trichloromethyl)-5-nitropyrazoline were performed. It was found, that the decompositions of the mentioned pyrazoline system in the solution and at the melted state proceed via completely different molecular mechanisms. These mechanisms have been explained in the framework of the Molecular Electron Density Theory (MEDT) with the computational level of B3LYP/6-31G(d). A Bonding Evolution Theory (BET) examination of dehydrochlorination of the 3,3-diphenyl-4-(trichloromethyl)-5-nitropyrazoline permits elucidation of the molecular mechanism. It was found, that on the contrary for most known HCl extrusion processes in solution, this reaction is realised via single-step mechanism.     

Physical aging in amorphous poly(ethylene furanoate): Enthalpic recovery,density, and oxygen transport considerations

The current work utilizes three separate techniques to study the physical aging process in amorphous poly(ethylene furanoate) (PEF), which is a recently introduced engineering thermoplastic with enhanced properties compared to petroleum‐sourced poly(ethylene terephthalate). Differential scanning calorimetry aging experiments were conducted at multiple aging temperatures and times, and the resultant enthalpic recovery values compared to the theoretical maximum enthalpy loss evaluated from calculations involving extrapolation of the equilibrium liquid line. Density measurements reveal densification of the matrix for the aged versus unaged samples, and provide an estimate for the reduction in free volume for the aged samples. Complementary oxygen permeation and pressure‐decay sorption experiments provide independent verification of the free volume reduction mechanism for physical aging in glassy polymers. The current work provides the first detailed aging study for PEF. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 389–399     

Monte Carlo simulation of electric conductivity for pure and doping fullerene (C60)

In this paper, we have used Monte Carlo (MC) method to simulate and study the temperature and doping effects on the electric conductivity of fullerene (C60). The results show that the band gap has reduced by the doping and the charge carrier transport is facilitated from valence band to conduction band by the temperature where is touched a 300 K. In this case, the conductivity reached a value of $4\times {10}^{-7}\text{S}{\text{cm}}^{-1}$. The electric conductivity of C60 can increase by the triphenylmethane dye crystal violet (CV) alkali metal to reach $4\times {10}^{-3}\text{S}{\text{cm}}^{-1}$ at 303 K. Our results of MC simulation have a good agreement with those extracted from literature [10], [33].     

Mono-Aryl/Alkylthio-Substituted (Hetero)acenes of Exceptional Thermal and Photochemical Stability by the Thio-Friedel–Crafts/Bradsher Cyclization Reaction

The highly substituted mono-aryl/alkylthio-(hetero)acenes prepared in this study have been found to be thermally more stable (T_decomp.=331–354 °C) than the known di-aryl/alkylthio-substituted acenes by an average of 25 °C. They are also much more photostable at 254 and 365 nm (in both argon and air) than the parent anthracene and other reported anthracenes. The most photostable aryl/alkylthio-anthracenes at 254 nm were found to be 60–70 (in air) and 130 (in argon) times more stable in solution than the unsubstituted anthracene, and much more stable than known EDG/EWG-substituted anthracenes (EDG=electron-donating group, EWG=electron-withdrawing group) with an extended aromatic core. Furthermore, the acenes showed significantly higher photostability at 365 nm in both air and argon. The anthracenes were obtained by the novel thio-Friedel–Crafts/Bradsher cyclization reaction of hitherto unknown [o-(1,3-dithian-2-yl)aryl](aryl)methyl thioethers. The developed approach provides a general access to mono-aryl/alkylthio-substituted (hetero)acene frameworks containing at least three fused (hetero)aromatic rings. The characteristic feature of this approach, which leads to highly substituted acenes, is that the substituents, unlike in other methods, may be introduced at an early stage of the synthesis. DFT and TD-DFT calculations confirmed the stabilizing role of the aryl/alkylthio substituent in the mono-aryl/alkylthio-substituted anthracenes, which are the most stable anthracenes prepared to date. Their high photostability is mainly due to the quenching of singlet oxygen by the acene and the quenching of the acene S₁ state by molecular oxygen.