Jacek G. Sośnicki

Metal-free visible-light photoredox arylation/aza-semipinacol cascade affords C4-arylated, C6-hydroxylated δ-lactams with quaternary C5 centers.

The synthesis of 2,4,4a,9-tetrahydro-3H-indeno[2,1-c]pyridin-3-ones 7 is achieved through the aza-semipinacol-type rearrangement of readily available iodobenzomorphanones when treated with silver salts. A comprehensive study was performed on the optimization of the synthesis of iodobenzomorphans and subsequent rearrangement products, while addressing the scope and limitations of both reactions. It has been shown that the resulting indeno[2,1-c]pyridine-3-ones, acting as enelactams, are suitable precursors for further stereoselective functionalization, e.g., reduction, using an NaBH₄/NiCl₂ system, and arylation activated by TIPSOTf.

Background: Paclitaxel (PTX), a crucial microtubule-stabilising agent in cancer treatment, is limited by its adverse effects and hydrophobic nature, which necessitate the use of toxic solvents. This study proposes a novel approach combining PTX with new microtubule-destabilising compounds at low, safe doses that are ineffective when used individually. Objective: The aim was to evaluate the therapeutic efficacy of combining PTX with previously described pyridine (S1, S22) and benzofuran derivatives (13b, 14), which have demonstrated promising anticancer properties by inhibiting microtubule polymerisation. Methods: The PrestoBlue assay was used to determine the optimal concentrations of each compound, enabling synergistic interactions with a low dose of PTX in HeLa cervical cancer cells. The combined effects of the compounds and PTX on apoptosis, cell cycle distribution, and mitotic spindle formation were then evaluated. Results: The results showed that compounds 13b (1 µM), 14 (0.1 µM), S1 (2 µM), and S22 (2 µM) enhanced the proapoptotic and antimitotic effects of 1 nM PTX, which was ineffective alone. Notably, live-cell imaging revealed that the concurrent use of S1 and PTX produced effects similar to those of a higher PTX concentration (5 nM). Conclusions: These findings suggest that these compounds enhance the anticancer efficacy of low-dose PTX, potentially paving the way for more effective and safer cancer therapies.

A method for the synthesis of C4-benzhydryl-functionalized 3,4-dihydropyridin-2-ones using complementary addition of benzhydryllithium and/or benzhydrylmagnesiate reagents to 2-pyridones, with high regioselectivity triggered by substituents, is described. A partially stereoselective cyclization was successfully demonstrated using TfOH and/or TIPSOTf as Brønsted and Lewis acids, respectively, leading to C6-phenyl-functionalized 7,8-benzomorphanones. It is also shown that the use of functionalized δ-enelactams obtained with an active methoxy-substituted benzyl group at C3 enabled the preparation of a new C3–C6 bridged system within the δ-lactam framework.

A method for the synthesis of C4-benzhydryl functionalized 3,4-dihydropyridin-2-ones using complementary addition of benzhydryllithium and/or benzhydrylmagnesiate reagents to 2-pyridones, with high regioselectivity triggered by substituents, is described. A partially stereoselective cyclization was successfully demonstrated using TfOH and/or TIPSOTf as Brønsted and Lewis acids, respectively, leading to C6-phenyl functionalized 7,8-benzomorphanones. It is also shown that the use of functionalized -enelactams obtained with an active methoxy-substituted benzyl group at C3, enabled the preparation of a new C3-C6 bridged system within -lactam framework.

A new type of UV-curable pressure-sensitive adhesive containing Si atoms (Si-PSAs) was prepared by a solution-free UV-initiated telomerization process of n-butyl acrylate, acrylic acid, methyl methacrylate, and 4-acrylooxybenzophenone using triethylsilane (TES) as a telogen and an acylphosphine oxide (APO) as a radical photoinitiator. Selected commercial adhesion promoters were tested as additives in the formulation of adhesive compositions, i.e., (i) an organic copolymer with polar groups (carboxyl and hydroxyl); (ii) a hydroxymetal-organic compound; and (iii) a quaternary ammonium salt and (iv) a chlorinated polyolefin. No fillers, crosslinking agents, or photoinitiators were used in the adhesive compositions. NMR techniques confirmed the incorporation of silicon atoms into the polyacrylate structure. The influence of adhesion promoters on the kinetics of the UV-crosslinking process of Si-PSAs was investigated by a photo-DSC technique. The obtained Si-PSAs were characterized by adhesion (to steel, glass, PMMA, and PE), tack, and cohesion at 20 °C. Finally, the wetting angle of Si-PSAs with water was checked and their thermal stability was proved (TGA). Unexpectedly, the quaternary ammonium salt had the most favorable effect on improving the thermal stability of Si-PSAs (302 °C) and adhesion to glass and PMMA. In contrast, Si-PSAs containing the hydroxymetal-organic compound showed excellent adhesion to steel.

Novel method of obtaining functional acrylic resins (FARs) containing carboxyl- and benzophenone groups (in-chain functionalization) and terminal Br atoms was verified. Acrylic oligomers were prepared by a solution-free, UV-initiated telomerization process of basic monomer (n-butyl acrylate) and functional monomers (acrylic acid and 4-acrylooxybenzophenone) in the presence of radical photoinitiator and different amount of tetrabromomethane (CBr₄) as telogen. The effect of telogen content on UV-telomerization kinetics as well as physicochemical and thermal (T_g) properties of FARs was investigated. A telogen content higher than 5 wt. parts does not affect the UV-telomerization rate (photo-DSC), the molecular weights of telomers (GPC), or their glass transition temperature (DSC), but it significantly increases the conversion of monomers (up to 88%) and lowers the viscosity of FARs (approx. 6 Pa·s). NMR studies confirmed the inclusion of CBr₄ in the structure of functional acrylic telomers.

In this paper, epoxy-acrylate structural adhesives tapes (SATs) were obtained from Bisphenol A-based liquid epoxy resin and epoxy acrylic resins (EARs). A new method of EARs preparation, i.e., the free radical bulk photopolymerization process (FRBP), was studied in detail. The influence of methacrylic monomers (methyl methacrylate, ethyl methacrylate, butyl methacrylate, lauryl methacrylate, (2-acetoacetoxy)ethyl methacrylate) and vinyl monomers (N-vinylpyrrolidone and styrene) on the FRBP process of base monomers (i.e., butyl acrylate, glycidyl methacrylate and 2-hydroxyethyl acrylate) was investigated. The kinetics of photopolymerization process was monitored by photo-differential scanning calorimetry method. The properties of the obtained EARs (viscosity and average molecular weights), as well as monomers conversion using ¹H NMR, were determined. It was revealed that styrene significantly decreases the photopolymerization rate and increases the final monomers conversion (+27%). However, the resulting tetrapolymers BA-co-GMA-co-HEA-co-STY have low molecular weights and low polydispersity (2.2). Methacrylate monomers with shorter aliphatic chains (4) also decrease the rate of photopolymerization due to the length of the aliphatic chain increasing. Surprisingly, the best results of adhesion to steel and shear strength were obtained for SAT based on epoxy acrylate resin with styrene (11 N/25 mm and 20.8 MPa, respectively). However, the thermomechanical properties of SAT with styrene were weaker than those with methacrylates.

The synthesis of bromo-substituted indeno[1,2-b]pyridin-2-ones and 3-iodo-5-benzyl-substituted 2-pyridones, starting from easily available 6-benzyl-3,6-dihydropyridin-2(1H)-ones, triggered by NBS and NIS, respectively, is described. In both syntheses, a transfer of a benzyl group from the C6 to C5 lactam position occurred, indicating a novel aza-semipinacol-type rearrangement. Identification of intermediate compounds in both transformations supported the proposed reaction mechanisms. In the process of checking the scope of the method's application, functionalized indeno[1,2-b]pyridin-2-ones and 5-benzyl-2-pyridones were obtained.

Poly(xylitol dicarboxylate-co-diol dicarboxylate) elastomers can by synthesized using wide variety of monomers with different chain lengths. Obtained materials are all biodegradable, thermally stable elastomers, but their specific properties like glass transition temperature, degradation susceptibility, and mechanical moduli can be tailored for a specific application. Therefore, we synthesized eight elastomers using a combination of two dicarboxylic acids, namely suberic and sebacic acid, and four different diols, namely ethanediol, 1,3-propanediol, 1,4-buanediol, and 1,5-pentanediol. Materials were further modified by e-beam treatment with a dose of 100 kGy. Materials both before and after radiation modification were tested using tensile tests, gel fraction determination, ¹H NMR, and ¹³C NMR. Thermal properties were tested by Differential Scanning Calorimetry (DSC), Dynamic Thermomechanical Analysis (DMTA) and Thermogravimetric Analysis (TGA). Degradation susceptibility to both enzymatic and hydrolytic degradation was also determined.