High-performance photoinitiating systems for new generation dental fillings.

OBJECTIVES: To obtain new generation dental composites with improved performance properties compared to currently available dental fillings on the market and to determine the influence of new initiating systems on final product parameters such as degree of cure, hardness, color, and shrinkage. METHODS: In order to verify the effectiveness of the developed initiating systems, typical spectroscopic, electrochemical, and kinetic studies using the real-time FT-IR method were shown. Moreover, paste dental fillings were prepared, the compositions were irradiated with the dental lamp, and the degrees of cross-linking were measured by Raman spectroscopy. The polymerization shrinkage was also determined using the rheometer. In addition, their hardness was examined on the Shore scale. Finally, the color analysis of the composites in the L*a*b* color space was compared with the VITA CLASSIC colorant. RESULTS: It was shown that, due to their excellent spectroscopic and electrochemical properties, new quinazolin-2-one can act as co-initiators in cationic and radical photopolymerization. It was demonstrated that the most effective composite containing the initiator system in the form of 3-SCH3Ph-Q, IOD, MDEA, and an inorganic filler as nanometric silica and a bonding agent is cured more than 90% after just 1 cycle of dental lamp exposure (30 s), the hardness of the composite after curing on the Shor Scale is 82 ± 4, and the polymerization shrinkage is less than 2.8%. SIGNIFICANCE: The article demonstrates effective new initiator systems as an alternative to CQ/amine for obtaining new-generation dental composites. The developed dental composites are a big competition to the currently used dental fillings on the market.

Double Role of Diphenylpyridine Derivatives as Fluorescent Sensors for Monitoring Photopolymerization and the Determination of the Efficiencies of the Generation of Superacids by Cationic Photoinitiators.

Novel fluorescent sensors with electron-donating or electron-withdrawing substituents incorporated into a chromophore group based on 2,6-diphenylpyridine were designed and synthesised. The spectroscopic properties of these compounds were studied. Moreover, the positive solvatochromism of 2,6-bis-(4-methylsulphanylphenyl)pyridine (PT-SCH3) in selected solvents was studied by measurement of the absorption and emission spectra and analysed using the Dimroth-Reichardt solvent parameter set. After that, the performance of a series of 2,6-diphenylpyridine derivatives as fluorescent molecular sensors for monitoring free-radical and cationic photopolymerization processes by the Fluorescence Probe Technique (FPT) was studied. As a consequence of this stage of research, the effect of substituents on the sensitivity of the 2,6-diphenylpyridine derivatives as sensors during photopolymerization has been evaluated and discussed. It has been found that compounds containing strong electron-donating substituent (PT-SCH3) slightly shift their fluorescence spectrum during the free-radical polymerization of monomer, which enables the monitoring of the polymerization progress using the fluorescence intensity ratio measured at two different wavelengths as the progress indicator. The position of the fluorescence spectrum of 2,6-diphenylpyridine derivatives with electron-withdrawing substituents is practically insensitive to changes occurring in their environment. Hence, it is recommended to use these compounds with different indicators of the progress of the photopolymerization process based on normalised intensity of fluorescence (Imax/I0). Among the compounds studied, 2,6-bis(4-methylsulphanylphenyl)pyridine (PT-SCH3) turned out to be the best fluorescent sensor for the purpose of monitoring free-radical polymerization by FPT. Consequently, the dual application of the selected 2,6-diphenylpyridine derivatives is proposed: (a) as fluorescent sensors for monitoring the free-radical photopolymerization progress, and (b) as spectroscopic sensors for the determination of efficiencies of the generation of superacids by cationic photoinitiators during the cationic photopolymerization process. Finally, a new method for determining the relative efficiency of the photogeneration of superacids during the photo cleavage of onium salt has been devised and applied for the evaluation of the performance of 2,6-diphenylpyridine derivatives.

New, highly versatile bimolecular photoinitiating systems for free-radical, cationic and thiol-ene photopolymerization processes under low light intensity UV and visible LEDs for 3D printing application.

1-Amino-4-methyl-naphthalene-2-carbonitrile derivatives are proposed for the role of photosensitizers of iodonium salt during the photopolymerization processes upon near UV-A and visible ranges. Remarkably, 1-amino-4-methyl-naphthalene-2-carbonitrile derivatives are highly versatile allowing access to photoinitiating systems for (i) the cationic photopolymerization of epoxide monomers with a ring opening mechanism and vinyl ether monomers with chain growth mechanisms (ii) the free-radical photopolymerization of acrylate monomers, (iii) the photopolymerization of interpenetrated polymer networks (IPNs) based on epoxide and acrylate monomers under air and under laminate in an oxygen-free atmosphere (iv) the thiol-ene photopolymerization processes. Excellent polymerization profiles are obtained during all types of photopolymerization processes. The initiation mechanisms are analyzed through steady state photolysis, cyclic voltammetry and fluorescence experiments. Moreover, the newly developed bimolecular photoinitiating systems were investigated by applying an additive manufacturing process under visible light sources. Furthermore, vat photopolymerization processes using IPN compositions, which are polymerizable by using new photoinitiating systems, provide high resolution and speeds. For these reasons, new bimolecular photoinitiating systems are promising initiators for photopolymerization-based 3D printing process to fabricate 3D structures.

Applicability of 1,6-Diphenylquinolin-2-one Derivatives as Fluorescent Sensors for Monitoring the Progress of Photopolymerisation Processes and as Photosensitisers for Bimolecular Photoinitiating Systems.

The applicability of new 1,6-diphenylquinolin-2-oneas derivatives as fluorescent molecular sensors for monitoring the progress of photopolymerisation processes by Fluorescence Probe Technique (FPT) has been tested. The progress of cationic, free-radical and thiol-ene photopolymerisation for commercially available monomers: triethylene glycol divinyl ether (TEGDVE), trimethylolpropane triacrylate (TMPTA) and trimethylpropane tris(3-mercaptopropropionate) (MERCAPTO) was monitored. It was found that new derivatives of 1,6-diphenylquinolin-2-one shifted their fluorescence spectra towards shorter wavelengths with the progress of polymerisation, which enabled monitoring the progress in terms of fluorescence intensity ratios as the progress indicator. Derivatives of 1,6-diphenylquinolin-2-one show sensitivity to changes in both polarity and viscosity in the surrounding microenvironment during photopolymerisation processes. Therefore, it was shown that they are good candidates to act as fluorescent sensors for monitoring the kinetics of very quick processes, such as photopolymerisation processes. Furthermore, the effect of the nature of substituents attached to the 1,6-diphenylquinolin-2-one ring on the characteristics of emission spectra was identified. Moreover, the sensitivity of fluorescent sensors was compared with commercially available model sensors, such as 7-diethylamino-4-methylcoumarin (Coumarin 1) and trans-2-(2',5'-dimethoxyphenyl)ethenyl-2,3,4,5,6-pentafluorobenzene (25ST). Moreover, it was also proven that selected derivatives of 1,6-diphenylquinolin-2-one exhibit an accelerating effect on the progress of cationic photopolymerisation of vinyl monomers (TEGDVE). Thus, the new 1,6-diphenylquinolin-2-one derivatives can be successfully used both as molecular fluorescence sensors to monitor the progress of photopolymerisation processes and as diaryliodonium salt photosensitisers to initiate cationic photopolymerisation processes in a UV-A range of 365 nm.

The Applicability of 2-amino-4,6-diphenyl-pyridine-3-carbonitrile Sensors for Monitoring Different Types of Photopolymerization Processes and Acceleration of Cationic and Free-Radical Photopolymerization Under Near UV Light.

The performance of a series of 2-amino-4,6-diphenyl-pyridine-3-carbonitrile derivatives as fluorescent molecular sensors for monitoring photopolymerization processes of different monomers by the Fluorescence Probe Technique (FPT) was studied. It has been shown that the new derivatives are characterized by much higher sensitivity than the commercially available 7-diethylamino-4-methylcoumarin (Coumarin 1) and trans-2-(2',5'-dimethoxyphenyl)ethenyl-2,3,4, 5,6-pentafluorobenzene (25ST) probes. It has been discovered that the 2-amino-4,6-diphenyl-pyridine-3-carbonitrile derivatives accelerate the cationic photopolymerization process initiated with diphenyliodonium photoinitiators at the wavelength where the photoinitiator alone does not work. They are particularly efficient for the photoinitiation of cationic photopolymerization of an epoxide and vinyl monomers. Consequently, the application of the 2-amino-4,6-diphenyl-pyridine-3-carbonitrile derivatives in a dual role: (a) as fluorescent sensors for monitoring the free-radical, thiol-ene and cationic polymerization progress, and (b) as long-wavelength co-initiators for diphenyliodonium salts initiators, is proposed.

5-Keto-3-cyano-2,4-diaminothiophenes as selective maternal embryonic leucine zipper kinase inhibitors.

Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17, IC50 ≈ 5 µM) with lead-like properties was optimized for MELK inhibition. The early identification of a plausible binding mode by molecular modeling offered guidance in the choice of modifications towards compound 52 which displayed a 98 nM IC50. A good selectivity profile was achieved for a representative member of the series (29) in a 486 protein kinase panel. Future elaboration of 52 has the potential to deliver compounds for further development with chemotherapeutic aims.

1-Sulfonyl-6-Piperazinyl-7-Azaindoles as potent and pseudo-selective 5-HT6 receptor antagonists.

A series of 1-Sulfonyl-6-Piperazinyl-7-Azaindoles, showing strong antagonistic activity to 5-HT6 receptor (5-HT6R) was synthesized and characterized. The series was optimized to reduce activity on D2 receptor. Based on the selectivity against this off-target and the analysis of the ADME-tox profile, compound 1c was selected for in vivo efficacy assessment, which demonstrated procognitive effects as shown in reversal of scopolamine induced amnesia in an elevated plus maze test in mice. Compound 3, the demethylated version of compound 1c, was profiled against a panel of 106 receptors, channels and transporters, indicating only D3 receptor as a major off-target. Compound 3 has been selected for this study over compound 1c because of the higher 5-HT6R/D2R binding ratio. These results have defined a new direction for the design of our pseudo-selective 5-HT6R antagonists.