Synthesis and Evaluation of Bombesin Analogues Conjugated to Two Different Triazolyl‐Derived Chelators for 99mTc Labeling

Overexpression of the gastrin‐releasing peptide receptor (GRPR) in a variety of human carcinomas has provided a means of diagnosis and treatment. Previously we reported a metabolically stable (N^αHis)Ac‐βAla‐βAla‐[Cha¹³,Nle¹⁴]BBS(7–14) analogue with high affinity for the GRPR. We have also shown that the biodistribution pattern of this fairly lipophilic, radiolabeled peptide can be enhanced by glycation, which is easily carried out by Cu^I‐catalyzed cycloaddition. Herein, we further elaborate this “click approach” in the synthesis of a new series of triazole‐based chelating systems as alternatives to the (N^αHis)Ac chelator for labeling with the ^99mTc(CO)₃ core. The bombesin analogues, containing these new chelating systems, were evaluated with regard to their synthesis and in vitro and in vivo properties, and were compared with their (N^αHis)Ac counterparts. The influence of the chelator on biodistribution properties was less than that of glycation, which clearly improved the tumor‐to‐background ratios.     

Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.     

Oil Diffusion in Fat Crystal Matrices: Characterization by NMR Relaxometry and Diffusometry

A novel technique based on high resolution (HR)-NMR diffusometry is presented to investigate oil diffusion on the (sub)-micron scale level in fat crystal networks in situ and in a non-destructive way. The use of a high-gradient probe enables the observation of the time (Δ)-dependent diffusion behavior in fat blends (FBs) of different solid fat content (SFC), as obtained by mixing soft palm mid fraction and high-oleic sunflower oil. Hereby, the NMR-diffusion data are analyzed using CONTIN to obtain a continuous distribution of diffusion coefficients. As such, the hindrance of the oil diffusion by the fat crystal network is examined. The characterization of the lipid matrices is completed with ¹H-LR-NMR relaxometry, X-ray diffraction, and microstructural visualization. For the investigated FBs, the average diffusion coefficient D(Δ) decreased with increasing SFC, indicating an increased tortuosity of the diffusive path due to an increasing density of the fat crystal networks as observed by polarized light microscopy. This is also supported by an increase in crystal surface area which is indicated by T₂-relaxation analysis. This study shows that NMR diffusometry is a promising technique for investigation of structure-function relationships in fat systems. Practical Applications: The study shows that NMR diffusometry is a promising technique for investigation of structure-function relationships in fat systems. For the first time, oil diffusion in fat crystal networks has been studied by HR-NMR diffusometry with high gradients to collect the diffusional echo signals, while CONTIN-analysis has been used for the first time to process the data.     

The coordinatively saturated vanadium MIL-47 as a low leaching heterogeneous catalyst in the oxidation of cyclohexene

A Metal Organic Framework, containing coordinatively saturated V^+IV sites linked together by terephthalic linkers (V-MIL-47), is evaluated as a catalyst in the epoxidation of cyclohexene. Different solvents and conditions are tested and compared. If the oxidant TBHP is dissolved in water, a significant leaching of V-species into the solution is observed, and also radical pathways are prominently operative leading to the formation of an adduct between the peroxide and cyclohexene. If, however, the oxidant is dissolved in decane, leaching is negligible and the structural integrity of the V-MIL-47 is maintained during successive runs. The selectivity toward the epoxide is very high in these circumstances. Extensive computational modeling is performed to show that several reaction cycles are possible. EPR and NMR measurements confirm that at least two parallel catalytic cycles are co-existing: one with V^+IV sites and one with pre-oxidized V^+V sites, and this is in complete agreement with the theoretical predictions.     

Food systems: New-Ruralism versus New-Urbanism

There is a growing debate on whether agricultural land in urban fringes should be maintained or converted to other uses. While 'pro-ruralists' believe agricultural land conversion can threaten food security and cause rural-urban migration, 'pro-urbanists' find it a necessary change for transition from a primitive agricultural-based community to an advanced industrial-based society which has the capacity to create mass productions. New-Ruralists follow an agricultural-based development approach that promotes small-medium farming and acknowledges rural lifestyle while New-Urbanists give a priority to large industrial-based sectors and encourage urban lifestyle. Given the unlike concerns of different societies, the paper concludes that the approaches might have different priorities in the less developed, developing, and developed world.     

Oxidation resistance of Ti3AlC2 and Ti3Al0.8Sn0.2C2 MAX phases: A comparison

Ti₃AlC₂ and Ti₃Al_0.8Sn_0.2C₂ MAX phase powders are densified using Spark Plasma Sintering (SPS) technique to obtain dense bulk materials. Oxidation tests are then performed over the temperature range 800°C-1000°C under synthetic air on the two different materials in order to compare their oxidation resistance. It is demonstrated that, in the case of the Ti₃Al_0.8Sn_0.2C₂ solid solution, the oxide layers consist in TiO₂, Al₂O₃, and SnO₂. The presence of Sn atoms in the A planes of the solid solution leads to an easy diffusion of Sn out of the MAX phase which promote the formation of the nonprotective and fast growing SnO₂ oxide. Moreover, the small Al/Ti atom's ratio promotes the growth of a nonprotective rutile-TiO₂ scale as well. In the case of the Ti₃AlC₂ MAX phase, the oxide layer consists in a protective alumina scale; a few TiO₂ grains being observed on the top of the Al₂O₃ layer. The parabolic oxidation rate constants are about 3 orders of magnitude smaller for Ti₃AlC₂ compared to Ti₃Al_0.8Sn_0.2C₂.     

Evidence of the influence of the cationic composition on the anionic affinity of layered double hydroxides

The effect of the cationic composition on the anionic affinity is evaluated by studying the reconstruction of the layered double hydroxide structure from mixed oxides obtained by the heat treatment of the Mg₄Al₂-layered double hydroxides solid solution, in aqueous solutions containing carbonates, sulfates, and nitrates. After synthesis, all the samples present the same c parameter whatever the iron content. After a thermal treatment at moderate temperature, amorphous mixed oxides are obtained from all the samples. The influence of the cationic composition is clearly demonstrated on the anionic affinity as the Mg₄Al₂-amorphous mixed oxides reconstructs the layered double hydroxide structure with 90 % carbonates and 10 % sulfates whereas the Mg₄Fe₂-amorphous mixed oxides reconstruct the layered double hydroxide structure with 89 % carbonates, 7 % sulfates, and 4 % nitrates. The nitrate ratio increases as the iron content increases.