Silicon complexes of corrole were obtained for the first time by reaction of the free-base corrole with hexachlorodisilane. The peripheral substituents of corrole strongly influence the nature of the reaction products: β-octaalkyl corrole was mainly isolated as the μ-oxo dimer, while a hydroxo complex was obtained in the case of 5,10,15-tris-(pentafluorophenyl)corrole. In the case of meso-tritolyl corrole, a mixture of monomer/μ-oxo dimer was obtained. The silicon corrole complexes are more stable toward hydrolysis than the corresponding porphyrin derivatives and are endowed with brilliant luminescence properties. The high affinity of silicon for fluoride ion allowed investigation of the ability of an Si corrole to serve as a sensor for F detection. The strong color variation due to the interaction with the halide ion makes the Si corrole an interesting material for the naked-eye detection of inorganic fluoride.

The interest of research groups and pharmaceutical companies to discover novel GSK-3β inhibitors has increased over the years considering the involvement of this enzyme in many pathophysiological processes and diseases. Along this line, we recently reported on 1H-indazole-3-carboxamide (INDZ) derivatives 1–6, showing good GSK-3β inhibition activity. However, they suffered from generally poor central nervous system (CNS) permeability. Here, we describe the design, synthesis, and in vitro characterization of novel imidazo[1,5-a]pyridine-1-carboxamide (IMID 1) and imidazo[1,5-a]pyridine-3-carboxamide (IMID 2) compounds (7–18) to overcome such liability. In detail, structure-based approaches and fine-tuning of physicochemical properties guided the design of derivatives 7–18 resulting in ameliorated absorption, distribution, metabolism, and excretion (ADME) properties. A crystal structure of 16 in complex with GSK-3β enzyme (PDB entry 6Y9S) confirmed the in silico models. Despite the nanomolar inhibition activity, the new core compounds showed a reduction in potency with respect to INDZ derivatives 1–6. In this context, Molecular Dynamics (MD) and Quantum Mechanics (QM) based approaches along with NMR investigation helped to rationalize the observed structure activity relationship (SAR). With these findings, the key role of the acidic hydrogen of the central core for a tight interaction within the ATP pocket of the enzyme reflecting in good GSK-3β affinity was demonstrated.

The elusive, multiple fully extended (2.0(5) -helix) peptide conformation was searched with a series of C(α,α) -diethylglycine homo-oligomers (n = 1 to 5) functionalized by an electron transfer (ET) donor···acceptor (D···A) pair in acetonitrile and chloroform solutions. In the former solvent, all peptides investigated were shown to populate the 3(10) -helix conformation, whereas in chloroform the two shortest members of the series (n = 1 and n = 2) adopt predominantly the 2.0(5) -helix. Interestingly, for the longest components (n = 3 to n = 5) in this latter solvent, an equilibrium between the 2.0(5) - and 3(10) -helices takes place, the latter conformation becoming progressively more populated as the peptide main-chain length increases. Time-resolved fluorescence (TRF) experiments and molecular mechanics (MM) calculations were used in a combined approach to analyze the ET efficiencies and to associate a specific conformer (from MM) to an experimentally determined ET rate constant (from TRF). Therefore, because of the high sensitivity of the ET process to the D···A distance, ET can be used as a kinetic spectroscopic ruler, allowing for the characterization of the transition from a pure 3(10) -helix conformation to a 2.0(5) -/3(10) -helix equilibrium for the longest Deg homo-peptides of this series upon changing the solvent from acetonitrile to chloroform. To our knowledge, this is the first time that the electronic coupling factor β for ET across a peptide chain in the 2.0(5) -helix conformation is provided.

A new series of iron triferrocenylcorroles with three different axial ligands, NO, Cl−and σ-Ph, is synthesized and characterized using1H NMR, electrochemical and spectroelectrochemical techniques in nonaqueous media.

Two synthetic routes for the preparation of the water soluble 5,10,15‐tris(4‐sulfonatophenyl)corrole are reported. The first approach explores the chlorosulfonation reaction on the phosphorus complex of 5,10,15‐tris(4‐trimethylsilylphenyl)corrole. Following this route, the P complex of the target corrole has been obtained in low yields, while the major product was the tetrasubstituted complex, with the additional sulfonyl group regioselectively introduced at the 2‐position. To widen the scope of the reaction, the direct preparation of the 5,10,15‐tris(4‐sulfonatophenyl)corrole has been pointed out, affording both the target corrole and the intermediate chlorosulfonyl derivative in reasonable yields. The photophysical properties and the protonation equilibria of both corroles have been investigated, showing that 5,10,15‐tris(4‐sulfonatophenyl)corrole does not aggregate in acidic solutions, different from the analogous porphyrin.