Functional Acrylic Resins Prepared via Photo-Induced Telomerization Using Tetrabromomethane as Telogen.

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 (Tg) 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.

Influence of Methacrylate and Vinyl Monomers on Radical Bulk Photopolymerization Process and Properties of Epoxy-Acrylate Structural Adhesives.

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 (

Divergent Synthesis of Functionalized Indenopyridin-2-ones and 2-Pyridones via Benzyl Group Transfer: Two Cases of Aza-semipinacol-Type Rearrangement.

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.

E-Beam Effects on Poly(Xylitol Dicarboxylate-co-diol Dicarboxylate) Elastomers Tailored by Adjusting Monomer Chain Length.

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.

Physical Effects of Radiation Modification of Biodegradable Xylitol-Based Materials Synthesized Using a Combination of Different Monomers.

There is a possibility of obtaining xylitol-based elastomers sharing common characteristics of biodegradability, thermal stability, and elastomeric behavior by using monomers with different chain-lengths. Therefore, we have synthesized eight elastomers using a combination of four different diols (ethanediol, 1.3-propanediol, 1.4-buanediol, and 1.5-pentanediol) and two different dicarboxylic acids (succinic acid and adipic acid). The obtained materials were further modified by performing e-beam treatment with a dose of 100 kGy. Materials both before and after radiation modification were tested by DSC, DMTA, TGA, tensile tests, gel fraction determination, hydrolytic and enzymatic degradation tests, 1H NMR and 13C NMR and FTIR.

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones.

Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine aalog (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC50 equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.

Tailoring the Physico-Chemical Properties of Poly(xylitol-dicarboxylate-co-butylene dicarboxylate) Polyesters by Adjusting the Cross-Linking Time.

Determining the cross-linking time resulting in the best achievable properties in elastomers is a very important factor when considering their mass production. In this paper, five biodegradable polymers were synthesized-poly(xylitol-dicarboxylate-co-butylene dicarboxylate) polymers, based on xylitol obtained from renewable sources. Five different dicarboxylic acids with even numbers of carbon atoms in the aliphatic chain were used: succinic acid, adipic acid, suberic acid, sebacic acid, and dodecanedioic acid. Samples were taken directly after polycondensation (prepolymer samples) and at different stages of the cross-linking process. Physiochemical properties were determined by a gel fraction test, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), quasi-static tensile tests, nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR), and an in vitro biodegradation test. The best cross-linking time was determined to be 288h. Properties and degradation time can be tailored for specific applications by adjusting the dicarboxylic acid chain length.

Influence of e-Beam Irradiation on the Physicochemical Properties of Poly(polyol Succinate-co-Butylene Succinate) Ester Elastomers.

The purpose of this research was synthesis and electron beam modification of novel ester elastomers consisting of sugar alcohol-succinic acid block and butylene glycol-succinic acid block. Four different alditols were used in the synthesis-sorbitol, erythritol, xylitol, and glycerol. The materials were irradiated with doses of 50, 100, and 150 kGy in order to determine which dose is the most beneficial. As expected, irradiation of the materials has led to the cross-link density becoming higher and improvement of the mechanical properties. Additionally, the materials were also sterilized in the process. The great advantage of elastomers described in the paper is the fact that they do not need chemical cross-linking agents or sensitizers in order to undergo radiation modification. The following tests were performed on cross-linked poly(polyol succinate-co-butylene succinate) elastomers: quasi-static tensile test, determination of cross-link density, differential scanning calorimetry (DSC), dynamic thermomechanical analysis (DMTA), wettability (water contact angle), and Fourier transform infrared spectroscopy (FTIR). In order to confirm successful synthesis, prepolymers were analyzed by nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR).

Effect of E-Beam Irradiation on Thermal and Mechanical Properties of Ester Elastomers Containing Multifunctional Alcohols.

The aim of this work was to investigate the thermal and mechanical properties of novel, electron beam-modified ester elastomers containing multifunctional alcohols. Polymers tested in this work consist of two blocks: sebacic acid-butylene glycol block and sebacic acid-sugar alcohol block. Different sugar alcohols were utilized in the polymer synthesis: glycerol, sorbitol, xylitol, erythritol, and mannitol. The polymers have undergone an irradiation procedure. The materials were irradiated with doses of 50 kGy, 100 kGy, and 150 kGy. The expected effect of using ionizing radiation was crosslinking process and improvement of the mechanical properties. Additionally, a beneficial side effect of the irradiation process is sterilization of the affected materials. It is also worth noting that the materials described in this paper do not require either sensitizers or cross-linking agent in order to perform radiation modification. Radiation-modified poly(polyol sebacate-co-butylene sebacate) elastomers have been characterized in respect to the mechanical properties (quasi-static tensile tests), cross-link density, thermal properties (Differential Scanning Calorimetry (DSC)), chemical properties: Fourier transform infrared spectroscopy (FTIR), and wettability (water contact angle). Poly(polyol sebacate-co-butylene sebacate) preopolymers were characterized with nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR) and gel permeation chromatography (GPC). Thermal stability of cross-linked materials (directly after synthesis process) was tested with thermogravimetric analysis (TGA).

Magnesiate-Utilized/Benzyne-Mediated Approach to Indenopyridones from 2-Pyridones: An Attempt To Synthesize the Indenopyridine Core of Haouamine.

An efficient, short-staged synthesis of cis-fused indeno[2,1-b]- and indeno[1,2-c]pyridin-2-ones, starting from 2-pyridones, using magnesiates of type R3MgLi as nucleophilic and deprotonation agents, mediated by benzyne generated in situ, under optimized conditions, is described. Following the developed protocol, rare C4a-arylsubstituted indeno[2,1-b]pyridones, resembling the core of haouamine, were obtained. The protocol offering the one-pot synthesis directly from 2-pyridone is also described.

Diversity-Oriented Synthesis toward Fused and Bridged Benzobicyclic Piperidin(on)es.

An efficient diverse synthesis of cis-fused indenopiperidines and bridged benzomorphanones, starting from cyclopropane-fused benzomorphanothiones and benzomorphanones, respectively, using NaBH4/NiCl2·6H2O/EtOH as a reducing system, is described. High rigidity of substrates allowed axially controlled syntheses of their trans-mono-alkylated derivatives, subsequently enabling access to both trans-alkyl-functionalized benzobicyclic piperidin(on)es. Diversity-oriented synthesis of naphthalene ring-containing fused naphthoindenopiperidines and bridged naphthomorphanone directly from 2-pyridones was also performed.

Comparative evaluation of new dihydropyrimidine and dihydropyridine derivatives perturbing mitotic spindle formation.

AIM: The mitotic spindle plays a key role in cell division which makes it an important target in cancer therapy. In the present study the antiproliferative activity of 4-benzyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (1) and its pyridine bioisoster (2) were evaluated and compared with monastrol (MON), the first known cell-permeable small molecule which disrupts bipolar spindle formation by inhibiting Eg5-kinesin activity. RESULTS: Our data revealed that compound 2 showed higher antiproliferative activity than MON against MCF7 and A375 cell lines and comparable reversible cell cycle inhibition in G2/M phase. However, compound 2 produced distinct phenotype from monoastral spindles, and did not affect Eg5 ATPase activity. CONCLUSION: The activity of compound 2 may suggest its new promising anticancer mechanism (different than MON), targeting other component required for spindle bipolarity.

Synthesis of Polycyclic δ-Lactams with Bridged Benzomorphan Skeleton: Selectivity and Diversity Driven by Substituents.

An efficient synthesis of bromofunctionalized 2,6-methano- and 1,5-methano-benzomorphanones, starting from easily available 6-benzyl-3,6-dihydropyridin-2(1H)-ones, is described. Furthermore, the synthesis of bridged benzomorphanones with hitherto not known polycyclic systems containing 2- or 3-azabicyclo[4.1.0]heptane units is developed upon treatment of both 2,6- and 1,5-methanobromobenzomorphans with t-BuOK. The effects of substituents on the diversity and stereoselectivity of both transformations are studied.

Regioselective synthesis of novel 4,5-diaryl functionalized 3,4-dihydropyrimidine-2(1H)-thiones via a non-Biginelli-type approach and evaluation of their in vitro anticancer activity.

An easy and novel approach to synthesize 4,5-diaryl functionalized 3,4-dihydropyrimidine-2(1H)-thiones via addition of aryllithiums to 5-aryl substituted pyrimidine-2(1H)-thiones, which could be regarded as a method complementary to the most widely used Biginelli-type synthesis, is described. In the reaction of aryllithiums with N-(Me)Bn substituted pyrimidine-2(1H)-thiones a high degree of regioselectivity of addition, leading to 4-aryl adducts, was achieved. Selected compounds tested for their in vitro anticancer activity against four human cancer cell lines showed the greatest activity against breast cancer (MCF7). 1-Benzyl-4-(3-hydroxyphenyl)-5-phenyl substituted 3,4-dihydropyrimidine-2(1H)-thione (10g) exhibiting 10-fold more potent activity than the best known monastrol (MON) stands as a promising candidate for further scaffold and asymmetric synthesis.

Long-range deuterium isotope effects on (13)C chemical shifts of intramolecularly hydrogen-bonded N-substituted 3-(cycloamine)thiopropionamides or amides: a case of electric field effects.

A series of intramolecularly hydrogen-bonded N-substituted 3-(piperidine, morpholine, N-methylpiperazine)thiopropionamides and some corresponding amides have been studied with special emphasis on hydrogen bonding. The compounds have been selected in order to vary and to minimize the N...N distance. Geometries, charge distributions, and chemical shifts of these compounds are obtained from DFT-type BP3LYP calculations. 1H and 13C 1D and 2D NMR experiments were performed to obtain H,H coupling constants, 13C chemical shifts assignments, and deuterium isotope effects on13C chemical shifts. Variable-temperature NMR studies and 2D exchange NMR spectra have been used to describe the rather complicated conformational behavior mainly governed by the ring flipping of the piperidine (morpholine) rings and intramolecular hydrogen bonding. Unusual long-range deuterium isotope effects on 13C chemical shifts are observed over as far as eight bonds away from the site of deuteriation. The isotope effects are related to the N...N distances, thus being related to the hydrogen bonding and polarization of the N-H bond. Arguments are presented showing that the deuterium isotope effects on 13C chemical shifts originate in electric field effects.