Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153Sm]Sm-DOTA-TATE.

Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with 153Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [153Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [153Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.

Contribution of Membrane Vesicle to Reprogramming of Bacterial Membrane Fluidity in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen capable of resisting environmental insults by applying various strategies, including regulating membrane fluidity and producing membrane vesicles (MVs). This study examined the difference in membrane fluidity between planktonic and biofilm modes of growth in P. aeruginosa and whether the ability to alter membrane rigidity in P. aeruginosa could be transferred via MVs. To this end, planktonic and biofilm P. aeruginosa were compared with respect to the lipid composition of their membranes and their MVs and the expression of genes contributing to alteration of membrane fluidity. Additionally, viscosity maps of the bacterial membrane in planktonic and biofilm lifestyles and under the effect of incubation with bacterial MVs were obtained. Further, the growth rate and biofilm formation capability of P. aeruginosa in the presence of MVs were compared. Results showed that the membrane of the biofilm bacteria is significantly less fluid than the membrane of the planktonic bacteria and is enriched with saturated fatty acids. Moreover, the enzymes involved in altering the structure of existing lipids and favoring membrane rigidification are overexpressed in the biofilm bacteria. MVs of biofilm P. aeruginosa elicit membrane rigidification and delay the bacterial growth in the planktonic lifestyle; conversely, they enhance biofilm development in P. aeruginosa. Overall, the study describes the interplay between the planktonic and biofilm bacteria by shedding light on the role of MVs in altering membrane fluidity. IMPORTANCE Membrane rigidification is a survival strategy in Pseudomonas aeruginosa exposed to stress. Despite various studies dedicated to the mechanism behind this phenomenon, not much attention has been paid to the contribution of the bacterial membrane vesicles (MVs) in this regard. This study revealed that P. aeruginosa rigidifies its membrane in the biofilm mode of growth. Additionally, the capability of decreasing membrane fluidity is transferable to the bacterial population via the bacterial MVs, resulting in reprogramming of bacterial membrane fluidity. Given the importance of membrane rigidification for decreasing the pathogen's susceptibility to antimicrobials, elucidation of the conditions leading to such biophysicochemical modulation of the P. aeruginosa membrane should be considered for the purpose of developing therapeutic approaches against this resistant pathogen.

Synthesis and photochemistry of novel 1,2,3-triazole di-heterostilbenes. An experimental and computational study.

The synthesis, photoreactivity, and spectroscopic characterization of novel 1,2,3-triazole di-heterostilbenes bearing various aliphatic and aromatic substituents on the triazole rings were thoroughly explored. By introducing triazole rings into the o-divinylbenzene moiety, compared with the 2-furyl and 2-thienyl heteroanalogues, these compounds did not show any photochemical reactivity toward intramolecular cycloaddition reactions or electrocyclization processes. The research is further extended to the more in-depth examination of photochemical and photophysical characteristics of the investigated triazolo-stilbenes to explain the lack of reactivity in intramolecular photochemical cyclizations by configuration and substituent effects. Conformations of synthetically obtained novel triazoles are examined by Density Functional Theory (DFT). The time dependent-DFT approach was employed to obtain additional insight into the properties observed with UV/Vis spectroscopy. The frontier orbital energy was computationally investigated to determine the influence of cis-trans isomerism and the nature of substituents on the spectroscopic properties of the triazoles. Along with our previous studies of similar compounds containing furan and thiophene, respectively, this study shows that introducing various heteroaromatic rings induces diverse photochemistry and photophysics due to the conformational changes and change in electronic distribution within the molecular system.

Metal-free syntheses of N-functionalized and NH-1,2,3-triazoles: an update on recent developments.

An overview of the latest developments in the metal-free synthesis of non-benzo-fused N-functionalized and NH-1,2,3-triazoles is provided in this feature article. Synthetic studies that appeared from 2016 until August 2020 are organized according to a wide-ranging classification, comprising oxidative and eliminative azide-dipolarophile cycloadditions, diazo transfer reactions and N-tosylhydrazone-mediated syntheses. The newly developed methods constitute a significant contribution to the field of 1,2,3-triazole synthesis in terms of structural variation via either the exploration of novel reactions, or the exploitation of existing methodologies.

Triazolization of Enolizable Ketones with Primary Amines: A General Strategy toward Multifunctional 1,2,3-Triazoles.

The development of metal-free syntheses toward 1,2,3-triazoles has been a burgeoning research area throughout the past decade. Despite the numerous advances, the scarceness of methods for the preparation of 1,5-disubstituted 1,2,3-triazoles from readily available substrates remained a challenge that was addressed by our group in 2016. A metal-free three-component reaction, which we have dubbed the triazolization reaction, was established for the rapid synthesis of 1,5-disubstituted, fully functionalized and NH-1,2,3-triazoles. This novel approach stands out because it utilizes widely available starting materials, namely primary amines and enolizable ketones. Furthermore, the broad substrate scope is a major advantage, and was further expanded by the number of modified protocols that have been reported. Triazolization products have successfully found utility as intermediates in various synthetic transformations, and were the subject of a few interesting biological activity studies.

Ring-Degenerate Rearrangement Resulting from the Azo Coupling Reaction of a 3-Aryl-1,3a,6a-triazapentalene.

The 3-(4-(methoxycarbonyl)phenyl)triazapentalene is a highly fluorescent small molecule which is readily accessible via a two-step synthesis. In the search for postfunctionalization methods, a radical CH-arylation with diazonium salts was attempted. However, azo coupling resulted in a ring-degenerate rearrangement toward a 2-aryl-4-azotriazapentalene, which was confirmed via crystallographic analysis. A mechanism involving the generation of a nitrilimine is proposed. In addition, reduction of the azo group led to cleavage of the triazapentalene core. The present results further demonstrate the sensitivity of the triazapentalene fluorophore.

1,2,3-Triazole-Mediated Synthesis of 1-Methyleneisoquinolines: A Three-Step Synthesis of Papaverine and Analogues.

A metal-free three-step synthesis toward functionalized 1-methyleneisoquinolines from readily available substrates is reported. First, acetal-containing 1,2,3-triazoles were prepared via a high-yielding triazolization reaction and quantitatively converted into triazolo[5,1-a]isoquinolines. Next, the acid-promoted ring opening of these fused triazoles was studied in order to obtain coupling to a diverse scope of nucleophiles, including carbon nucleophiles such as veratrole. By means of non-nucleophilic strong acids under anhydrous conditions, a series of unprecedented isoquinolines and imidazo[5,1-a]isoquinolines was synthesized.

Separation of cobalt and nickel using a thermomorphic ionic-liquid-based aqueous biphasic system.

A [P44414][Cl]-NaCl-H2O ionic liquid-based aqueous biphasic system shows promising results for the separation of cobalt(II) and nickel(II) by homogeneous liquid-liquid extraction. The extracting phase consists of a hydrophilic ionic liquid that is salted-out by sodium chloride, indicating that there is no need for using hydrophobic ionic liquids.