Large‐Scale Synthesis of Enantiopure Molecular Cages: Chiroptical and Recognition Properties

A convenient and efficient gram‐scale synthesis for enantiopure hemicryptophane–tren (tren=tris(2‐aminoethyl)amine) derivatives has been developed. The four‐step synthesis is based on the optical resolution of a key intermediate, cyclotriveratrylene, for which the energy barrier for racemization has been measured to ensure that no racemization occurs during the two last steps of the synthetic pathway. The assignments of the absolute configurations have been performed by electronic circular dichroism and the enantiopurity was determined by NMR spectroscopy in the presence of enantiopure camphor sulfonic acid. To highlight the interest of such compounds, the recognition of norephedrine neurotransmitter was investigated and showed a remarkable enantioselectivity towards the C₃ symmetrical hosts. Finally, this highly modular synthetic pathway was used to provide eight enantiopure hemicryptophanes with different sizes, shapes, and functionalities. These results underline the high potential of this approach, which could lead to many applications in chiral recognition or asymmetric supramolecular catalysis.     

Poly(trimethylene carbonate)/Poly(malic acid) Amphiphilic Diblock Copolymers as Biocompatible Nanoparticles

Amphiphilic polycarbonate–poly(hydroxyalkanoate) diblock copolymers, namely, poly(trimethylene carbonate) (PTMC)‐b‐poly(β‐malic acid) (PMLA), are reported for the first time. The synthetic strategy relies on commercially available catalysts and initiator. The controlled ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by the organic guanidine base 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), associated with iPrOH as an initiator, provided iPrO?PTMC?OH, which served as a macroinitiator in the controlled ROP of benzyl β‐malolactonate (MLABe) catalyzed by the neodymium triflate salt (Nd(OTf)₃). The resulting hydrophobic iPrO?PTMC‐b‐PMLABe?OH copolymers were then hydrogenolyzed into the parent iPrO?PTMC‐b‐PMLA?OH copolymers. A range of well‐defined copolymers, featuring different sizes of segments (M_n,NMR up to 9300 g mol^?1; Ð_M=1.28–1.40), were thus isolated in gram quantities, as evidenced by NMR spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, and contact angle analyses. Subsequently, PTMC‐b‐PMLA copolymers with different hydrophilic weight fractions (11–75 %) self‐assembled in phosphate‐buffered saline upon nanoprecipitation into well‐defined nano‐objects with D_h=61–176 nm, a polydispersity index <0.25, and a negative surface charge, as characterized by dynamic light scattering and zeta‐potential analyses. In addition, these nanoparticles demonstrated no significant effect on cell viability at low concentrations, and a very low cytotoxicity at high concentrations only for PTMC‐b‐PMLA copolymers exhibiting hydrophilic fractions over 47 %, thus illustrating the potential of these copolymers as promising nanoparticles.     

A Far-Red Emitting Fluorescent Chemogenetic Reporter for In Vivo Molecular Imaging

Far-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae, and chicken embryos. Beyond enabling the genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein–protein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors.     

Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals

Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late-stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air-stable iridium precatalyst [Ir(COD)(OMe)]₂ is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa-/thia-zoles, thiophene, but also electron-rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.     

Cyclometalated Iridium(III) Complexes Containing Semicarbazone Ligands: Synthesis,Characterization, Photophysical and Biological Studies

The synthesis, crystal structure, photophysical properties, and biological activity of the novel bis‐cyclometalated complexes [Ir(ptpy)₂(vnsc)] ( 2 ) and [Ir(ptpy)₂(acsc)] ( 3 ) [ptpy = 2‐(p‐tolyl)pyridinato, vnsc = vanillin semicarbazone, acsc = acetone semicarbazone] are described. The new compounds were prepared by the reaction of [{Ir(μ‐Cl)(ptpy)₂}₂] ( 1 ) with the corresponding semicarbazone ligands under basic conditions. The molecular structure of compound 3 was confirmed by a single‐crystal X‐ray diffraction study. The complex crystallized from chloroform as a mono‐ solvate in the orthorhombic space group Pcab with eight molecules in the unit cell.     

Total synthesis of TMS-ent-bisabolangelone

The absolute configuration of bisabolangelone has been established by an eleven step total synthesis of the corresponding TMS protected antipode starting from (R)-(+)-pulegone. Comparison of the TMS-derivatives by GC on a chiral column, allowed us to assign the absolute configuration of the synthetic compound and thus of the corresponding natural product. The latter has been confirmed by the Mosher's ester analysis of the known secondary carbinol derivative.     

Cyclometalated Iridium(III) and Rhodium(III) Complexes Containing Naphthyridine Ligands: Synthesis,Characterization and Biological Studies

The synthesis, crystal structure, and biological activity of new bis‐cyclometalated compounds [M(ptpy)₂(4‐chloro‐2‐methyl‐1,8‐naphthyridine)]PF₆ [M = Rh ( 1 ); M = Ir ( 2 ); ptpy = 2‐(p‐tolyl)pyridinato] and [M(ptpy)₂(2‐methyl‐1,8‐naphthyridine)]PF₆ [M = Rh ( 3 ); M = Ir ( 4 )] are described. The new compounds were prepared by the reaction of [{M(μ‐Cl)(ptpy)₂}₂] (M = Rh, Ir) with the corresponding naphthyridine ligands. The molecular structures of compounds 1 , 3 , and 4 were confirmed by single‐crystal X‐ray diffraction studies.     

Acetylene Derivatives of Cationic Diazaoxatriangulenes and Diaza [4]Helicenes - Access to Red Emitters and Planar Chiral Stereochemical Traits

Cationic triangulenes, and related helicenes, constitute a rich class of dyes and fluorophores, usually absorbing and emitting light at low energy, in the orange to red domains. Recently, to broaden the scope of applications, regioselective late-stage functionalizations on these core moieties have been developed. For instance, with the introduction of electron-donating groups (EDGs), important bathochromic shifts are observed pushing absorptions towards or in the near-infrared (NIR) spectral domain while emissive properties disappear essentially completely. Herein, to upset this drawback, acetylene derivatives of cationic diazaoxa triangulenes (DAOTA) and [4]helicenes are prepared (16 examples). Contrary to other EDG-functionalized derivatives, C≡C− functionalized products remain broadly fluorescent, with red-shifted absorptions (Δλ_abs up to 25 nm) and emissions (Δλ_em up to 73 nm, Φ_PL up to 51 %). Quite interestingly, a general dynamic stereoisomerism phenomenon is evidenced for the compounds derived from achiral DAOTA cores. At low temperature in ¹H NMR spectroscopy (218 K), N−CH₂ protons become diastereotopic with chemical shifts differences (Δδ) as high as +1.64 ppm. The signal coalescence occurs around 273 K with a barrier of ∼12 kcal mol⁻¹. This phenomenon is due to planar chiral conformations (S_p and R_p configurations), induced by the geometry of the alkyl (n-propyl) side-chains next to the acetylenic substituents. Ion pairing studies with Δ-TRISPHAT anion not only confirm the occurrence of the chiral conformations but evidence a moderate but definite asymmetric induction from the chiral anion onto the cations. Finally, DFT calculations offer a valuable insight on the geometries, the corresponding stereodynamics and also on the very large difference in NMR for some of the diastereotopic protons.     

Lights and Shadows of DMSO as Solvent for Tin Halide Perovskites

In 2020 dimethyl sulfoxide (DMSO), the ever-present solvent for tin halide perovskites, was identified as an oxidant for Sn^II. Nonetheless, alternatives are lacking and few efforts have been devoted to replacing it. To understand this trend it is indispensable to learn the importance of DMSO on the development of tin halide perovskites. Its unique properties have allowed processing compact thin-films to be integrated into tin perovskite solar cells. Creative approaches for controlling the perovskite crystallization or increasing its stability to oxidation have been developed relying on DMSO-based inks. However, increasingly sophisticated strategies appear to lead the field to a plateau of power conversion efficiency in the range of 10–15 %. And, while DMSO-based formulations have performed in encouraging means so far, we should also start considering their potential limitations. In this concept article, we discuss the benefits and limitations of DMSO-based tin perovskite processing.     

Approximate inertial manifolds for reaction-diffusion equations in high space dimension

The concept of approximate inertial manifolds was introduced by Foiaset al. (1987) in the case of the two-dimensional Navier-Stokes equations. These manifolds are finite dimensional smooth manifolds such that the orbits enter a very thin neighborhood of the manifold after a transient time; this concept replaces the one of inertial manifold when either an inertial manifold does not exist or its existence is not known. Our aim in this paper is to prove that approximate inertial manifolds exist for reaction-diffusion equations in high space dimension by opposition with exact inertial manifolds whose existence has only been proved in low dimension and for which nonexistence results have been obtained in space dimensionn=4.