Characterization of New PPARγ Agonists: Analysis of Telmisartan’s Structural Components

Telmisartan was originally designed as an AT₁ antagonist but was later also characterized as a selective PPARγ modulator. This study focused on the identification of the essential structural motifs of telmisartan for PPARγ activation activity, elucidating the individual SAR of each different component (shown).

     

Characterization of New PPARγ Agonists: Benzimidazole Derivatives – the Importance of Position 2

Probing SAR : The 1‐(biphenyl‐4‐ylmethyl)‐1H‐benzo[d]imidazole moiety is known to be an essential structural component of telmisartan for PPARγ activation. This study focused on the substituents at position 2 of the benzimidazole in an attempt to optimize PPARγ activation. In particular, the elongation of the alkyl chain and the introduction of an aromatic ring system were studied (shown).

     

Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H₂ results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the ¹H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan ¹H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.     

Droplet Entrainment Analysis in a Flash Evaporator with an Image-Based Measurement Technique

Local droplet sizes and volumes of entrained liquid are captured with an image-based measurement technique for comparison with a conventional, integral method for entrainment analysis. Experiments in a forced circulation flash evaporation were performed for different operating conditions and with two different chemical systems. Droplet size and frequency rise with an increase in thermal energy input. The local readings confirm the trends found by the integral measurement method. The modification of the image-based probe enables the detection of small (≈ 10 µm) and at the same time fast droplets under challenging operating conditions, such as vacuum and superheated feed similar to industrial process conditions.     

Internal cation mobility in molten CsCl-NdCl3 system at 1073 K

CsCl-NdCl₃ is the next of binary MCl-NdCl₃ systems (M: alkali metal) investigated for determination of relative internal mobilities of cations (b_Cs, b_Nd) by countercurrent electromigration method (Klemm's method). The results have been presented as isotherms of internal mobilities of Cs⁺ and Nd³⁺ ions on NdCl₃ equivalent fraction (y_Nd). It has been found that internal mobility of cesium cations is higher than neodymium ones in the entire composition range (what is typical for nonsymmetrical MCl-LnCl₃ systems (M: Li, Na, K; Ln: La, Nd, Dy)) and decreases with increase of NdCl₃ concentration in the melt. Generally, dependence of internal mobility of lanthanide cations in melts with alkali metal chlorides on lanthanide (i.e. its atomic number and concentration) seems strongly related to stability of chloride complex anions of lanthanides in the melt. Investigated systems may be divided into two classes. The first class includes MCl-NdCl₃ systems (M: Li, Na) characterized by decrease of b_Nd with increase of NdCl₃ concentration. The second includes KCl-LnCl₃ systems (Ln: La, Nd, Dy) and presented here CsCl-NdCl₃ system, and is characterized by increase of b_Ln with concentration of Ln³⁺ cation. The dependence of b_Nd on NdCl₃ concentration at 1073 K was fitted (as for other systems) by a simple equation of the form: , where is the internal mobility of Ln³⁺ cations in pure molten LnCl₃, a the difference between internal mobility of Ln³⁺ cations in pure molten LnCl₃ and infinitely diluted LnCl₃ in molten alkali metal chloride (extrapolated), and yLnCl₃ is the equivalent fraction of LnCl₃.     

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.     

低浓度三氯乙烯活性炭吸附净化及数值模拟

对低浓度三氯乙烯在活性炭固定床中的吸附净化作了系统研究。测定了三氯乙烯-空气-活性炭系统吸附等温线及在40×120mm活性炭固定床中穿透曲线;建立了三氯乙烯活性炭固定床吸附数学模型并用此预测了穿透曲线,实验与计算结果对比表明模型预测与实验结果吻合良好。     

The Pupal Parasitoid Trichopria drosophilae Is Attracted to the Same Yeast Volatiles as Its Adult Host

Journal of Chemical Ecology - There is increasing evidence that microorganisms, particularly fungi and bacteria, emit volatile compounds that mediate the foraging behaviour of insects and therefore...