Thermally Responsive Selenide-containing Materials Based on Transalkylation of Selenonium Salts

Covalent adaptable networks (CANs) possess unique properties as a result of their internal dynamic bonds, such as self-healing and reprocessing abilities. In this study, we report a thermally responsive C−Se dynamic covalent chemistry (DCC) that relies on the transalkylation exchange between selenonium salts and selenides, which undergo a fast transalkylation reaction in the absence of any catalyst. Additionally, we demonstrate the presence of a dissociative mechanism in the absence of selenide groups. After incorporation of this DCC into selenide-containing polymer materials, it was observed that the cross-linked networks display varying dynamic exchange rates when using different alkylation reagents, suggesting that the reprocessing capacity of selenide-containing materials can be regulated. Also, by incorporating selenonium salts into polymer materials, we observed that the materials exhibited good healing ability at elevated temperatures as well as excellent solvent resistance at ambient temperature. This novel dynamic covalent chemistry thus provides a straightforward method for the healing and reprocessing of selenide-containing materials.     

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC₅₀ = 66.4 μM in HepG2 cells, IC₅₀ = 43.1 μM in HepG2 cells) at 10 μM.     

Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.     

In vivo solid phase microextraction sampling of human saliva for non-invasive and on-site monitoring

On-site sample preparation is an analytical approach based on direct sampling from the system under investigation. It has the advantage of combining sampling and sample preparation into a single step, thus generally is fast, minimizes the potential sources of error and eliminates the risks for analytes instability. For such analysis solid phase microextraction in thin film geometry (TF-SPME) can provide robust and convenient in vivo sampling, offering in the same time faster analysis and higher extraction recovery (i.e., better sensitivity) due to large surface to volume ratio.     

Optimization of Experimental Parameters to Explore Small‐Ligand/Aptamer Interactions through Use of 1H NMR Spectroscopy and Molecular Modeling

Aptamers constitute an emerging class of molecules designed and selected to recognize any given target that ranges from small compounds to large biomolecules, and even cells. However, the underlying physicochemical principles that govern the ligand‐binding process still have to be clarified. A major issue when dealing with short oligonucleotides is their intrinsic flexibility that renders their active conformation highly sensitive to experimental conditions. To overcome this problem and determine the best experimental parameters, an approach based on the design‐of‐experiments methodology has been developed. Here, the focus is on DNA aptamers that possess high specificity and affinity for small molecules, L ‐tyrosinamide, and adenosine monophosphate. Factors such as buffer, pH value, ionic strength, Mg²⁺‐ion concentration, and ligand/aptamer ratio have been considered to find the optimal experimental conditions. It was then possible to gain new insight into the conformational features of the two ligands by using ligand‐observed NMR spectroscopic techniques and molecular mechanics.     

Formation of the Main Cores Present in Natural Products by Tandem Additions

A rapid route to 5,5‐ and 5,6‐ bicyclic systems is provided by an 1,3‐alkyl‐shift process mediated by a hypervalent iodine reagent on aromatics. The structures obtained contain several unsaturations with different behaviors and reactivities. Such diversity allows further elaborations for the rapid formation of compact systems present in a variety of natural products. The potential for further transformations has been demonstrated by performing a double Michael addition. This cyclization process is regio‐ and stereoselective due to the presence of a former benzylic substituent. Furthermore, an extension of this approach has been accomplished on indole derivatives.     

Sunlight‐Driven Formation and Dissociation of a Dynamic Mixed‐Valence Thallium(III)/Thallium(I) Porphyrin Complex

Inspired by a Newton’s cradle device and interested in the development of redox‐controllable bimetallic molecular switches, a mixed‐valence thallium(III)/thallium(I) bis‐strap porphyrin complex, with Tl^III bound out of the plane of the N core and Tl^I hung to a strap on the opposite side, was formed by the addition of TlOAc to the free base and exposure to indirect sunlight. In this process, oxygen photosensitization by the porphyrin allows the oxidation of Tl^I to Tl^III. The bimetallic complex is dynamic as the metals exchange their positions symmetrically to the porphyrin plane with Tl^III funneling through the macrocycle. Further exposure of the complex to direct sunlight leads to thallium dissociation and to total recovery of the free base. Hence, the porphyrin plays a key role at all stages of the cycle of the complex: It hosts two metal ions, and by absorbing light, it allows the formation and dissociation of Tl^III. These results constitute the basis for the further design of innovative light‐driven bimetallic molecular devices.