Design, Synthesis, and Spectral Properties of Novel 2-Mercaptobenzothiazole Derivatives.

This paper is focused on the optimalization of methods for the synthesis, isolation, and purification of 2-mercaptobenzothiazole-based acrylic and methacrylic monomers. The structures of the newly synthesized compounds were confirmed through infrared (IR) and nuclear magnetic resonance spectroscopy (NMR). Spectroscopic properties of the resulting 2-mercaptobenzothiazole derivatives were determined based on their absorption spectra and molar absorption coefficients in solvents with varying polarities. A correlation was established between the calculated density functional theory (DFT) energies and Frontier Molecular Orbitals and the experimental observations, confirming their consistency. The practical utility of the synthesized compounds, particularly in future polymerization processes, hinges on a thorough understanding of these properties.

ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes.

The development of new substances with the ability to interact with a biological target is only the first stage in the process of the creation of new drugs. The 5-nitroisatin derivatives considered in this study are new inhibitors of cyclin-dependent kinase 2 (CDK2) intended for anticancer therapy. The research, carried out based on the ADMET (absorption, distribution, metabolism, excretion, toxicity) methods, allowed a basic assessment of the physicochemical parameters of the tested drugs to be made. The collected data clearly showed the good oral absorption, membrane permeability, and bioavailability of the tested substances. The analysis of the metabolite activity and toxicity of the tested drugs did not show any critical hazards in terms of the toxicity of the tested substances. The substances' low solubility in water meant that extended studies tested compounds were required, which helped to select solvents with a high dissolving capacity of the examined substances, such as DMSO or NMP. The use of aqueous binary mixtures based on these two solvents allowed a relatively high solubility with significantly reduced toxicity and environmental index compared to pure solvents to be maintained, which is important in the context of the search for green solvents for pharmaceutical use.

Designing and Synthesis of New Isatin Derivatives as Potential CDK2 Inhibitors.

Tumors are still one of the main causes of death; therefore, the search for new therapeutic agents that will enable the implementation of effective treatment is a significant challenge for modern pharmacy. One of the important factors contributing to the development of neoplastic diseases is the overexpression of enzymes responsible for the regulation of cell division processes such as cyclin-dependent kinases. Numerous studies and examples of already-developed drugs confirm that isatin is a convenient basis for the development of new groups of inhibitors for this class of enzyme. Therefore, in this work, a new group of potential inhibitors of the CDK2 enzyme, utilizing isatin derivatives and substituted benzoylhydrazines, has been designed based on the application of computational chemistry methods, such as docking and molecular dynamics, and their inhibiting ability was assessed. In the cases of the selected compounds, a synthesis method was developed, and the selected physicochemical properties of the newly synthesized derivatives were estimated. As part of the completed project, new compounds are developed which are potential inhibitors of the CDK2 enzyme.

New BODIPY Dyes Based on Benzoxazole as Photosensitizers in Radical Polymerization of Acrylate Monomers.

A series of 2-phenacylbenzoxazole difluoroboranes named BODIPY dyes (1-8) was designed and applied as photosensitizers (PS) for radical photopolymerization of acrylate monomer. The light absorption within the ultraviolet-visible (UV-Vis) range (λmax = 350-410 nm; εmax = 23,000-42,500 M-1cm-1), that is strongly influenced by the substituents on the C3 and C4 atoms of phenyl ring, matched the emission of the Omnicure S2000 light within 320-500 nm. The photosensitizer possess fluorescence quantum yield from about 0.005 to 0.99. The 2-phenacylbenzoxazole difluoroboranes, together with borate salt (Bor), iodonium salt (Iod) or pyridinium salt (Pyr) acting as co-initiators, can generate active radicals upon the irradiation with a High Pressure Mercury Lamp which initiates a high-performance UV-Vis light-induced radical polymerization at 320-500 nm. The polymers obtained are characterized by strong photoluminescence. It was found that the type of radical generator (co-initiator) has a significant effect on the kinetic of radical polymerization of acrylate monomer. Moreover, the chemical structure of the BODIPY dyes does not influence the photoinitiating ability of the photoinitiator. The concentration of the photoinitiating system affects the photoinitiating performance. These 2-phenacylbenzoxazole difluoroborane-based photoinitiating systems have promising applications in UV-Vis-light induced polymerization.

Can Plant Materials Be Valuable in the Treatment of Periodontal Diseases? Practical Review.

Periodontal diseases are one of the most significant challenges in dental health. It is estimated that only a few percent of the worldwide population have entirely healthy teeth, and according to WHO, oral diseases may affect up to 3.5 billion people worldwide. One of the most serious oral diseases is periodontitis, an inflammatory disease affecting periodontal tissues, caused by pathogenic bacteria and environmental factors such as the ageing population, abuse of tobacco products, and lack of adequate oral hygiene due low public awareness. Plant materials are widely and successfully used in the management of many conditions, including periodontitis. Plant materials for periodontitis exhibit antibacterial, anti-inflammatory, antioxidant activities and affect the periodontium structure. Numerous studies demonstrate the advantages of phytotherapy for periodontitis relief and indicate the usefulness of Baikal skullcap root, Pomegranate fruit peel and root cortex, Tea leaves, Chamomile flowers, Magnolia bark, Blackberry leaves and fruits, Cranberry fruits and Lippia sidoides essential oil. This review aims to analyze the use and applicability of selected plant materials in periodontitis management since it is of paramount importance to evaluate the evidence of the traditionally used plant materials in light of continuously growing interest in phytotherapy and its adjuvant role in the treatment of periodontitis.

Substituent and Solvent Polarity on the Spectroscopic Properties in Azo Derivatives of 2-Hydroxynaphthalene and Their Difluoroboranes Complexes.

Novel fluorescent dyes such as difluoroborane complexes of 1-phenylazonaphthalen-2-ol derivatives were successfully synthesized and characterized with a focus on the influence of a substituent and a solvent on the basic photophysical properties. 1H, 11B, 13C, 15N, and 19F nuclear magnetic resonance (NMR) spectra of substituted 1-phenylazonaphthalen-2-ol difluoroboranes and their parent azo dyes were recorded and discussed. The absorption and emission properties of synthesized compounds were investigated in solvents of varying polarity. They were found to be fluorescent despite the presence of the azo group. The azo group rotation was blocked by complexing with -BF2 to get a red shift in absorption. Solvent-dependent spectral properties of compounds were investigated using Lipper-Mataga and Bakhshiev plot. The calculated DFT energies and Frontier Molecular Orbitals calculations of the studied compounds were proved to be consistent with the experimental observations.

Physicochemical Characterization of a Co-Amorphous Atorvastatin-Irbesartan System with a Potential Application in Fixed-Dose Combination Therapy.

The aim of this study was to characterize a 1:1 molar ratio of a pharmacologically relevant co-amorphous atorvastatin-irbesartan (ATR-IRB) system obtained by quench cooling of the crystalline ATR/IRB physical mixture for potential use in the fixed-dose combination therapy. The system was characterized by employing standard differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and intrinsic dissolution rate studies. Quantum mechanical calculations were performed to obtain information regarding intermolecular interactions in the studied co-amorphous ATR-IRB system. The co-amorphous formulation showed a significant improvement in the intrinsic dissolution rate (IDR) of IRB over pure crystalline as well as its amorphous counterpart. An unusual behavior was observed for ATR, as the IDR of ATR in the co-amorphous formulation was slightly lower than that of amorphous ATR alone. Short-term physical aging studies of up to 8 h proved that the ATR-IRB co-amorphous system remained in the amorphous form. Furthermore, no physical aging occurred in the co-amorphous system. FT-IR, density functional theory calculations, and analysis of T g value of co-amorphous system using the Couchman-Karasz equation revealed the presence of molecular interactions between APIs, which may contribute to the increased physical stability.

Preparation and Characterization of Acrylic Pressure-Sensitive Adhesives Crosslinked with UV Radiation-Influence of Monomer Composition on Adhesive Properties.

In this study, syntheses of acrylate copolymers were performed based on the monomers butyl acrylate (BA), 2-ethylhexyl acrylate (2-EHA), and acrylic acid (AA) and the second-type unsaturated photoinitiator 4-acryloyloxybenzophenone (ABP). The structure of the obtained copolymers was confirmed via FT-IR spectroscopic analysis, and the viscosity and the content of non-volatile substances were determined. The adhesive films were then coated and cross-linked using ultraviolet radiation in the UV-C range at various doses (5-50 mJ/cm2). Due to the dependence of the self-adhesive properties of the adhesive layer on the basis weight, various basis weights of the layer in the range of 30-120 g/m2 were tested. Finally, the self-adhesive properties were assessed: tack, peel adhesion, shear strength (cohesion) at 20 °C and 70 °C, as well as the SAFT test and shrinkage. The aim of the study was to determine the effect of the type of monomer used, the dose of ultraviolet radiation, and the basis weight on the self-adhesive and usable properties of the obtained self-adhesive tapes.

Substituted 2-Phenacylbenzoxazole Difluoroboranes: Synthesis, Structure and Properties.

Novel fluorescent dyes such as benzoxazole-boron complexes, bearing ß-ketoiminate ligands, have been synthesized and characterized with a focus on the influence of a substituent on the basic photophysical properties. 1H, 11B, 13C, 15N, and 19F nuclear magnetic resonance (NMR) spectra of substituted 2-phenacylbenzoxazole difluoroboranes have been recorded and discussed. It is worth mentioning that a high correlation coefficient was found between 15N-NMR parameters and substituent constants. The photophysical properties of these new dyes have been investigated by fluorescence and ultraviolet-visible (UV-Vis) absorption spectroscopy. The geometry optimization, vibrational spectra, and the HOMO and LUMO energies were calculated based on density functional theory with the use of the B3LYP functional and 6-311++G(d,p) basis set.

Physical Ageing of Amorphous Indapamide Characterised by Differential Scanning Calorimetry.

The objective of this study was to characterise amorphous indapamide (IND) subjected to the physical ageing process by differential scanning calorimetry (DSC). The amorphous indapamide was annealed at different temperatures below the glass transition, i.e., 35, 40, 45, 65, 75 and 85 °C for different lengths of time, from 30 min up to a maximum of 32 h. DSC was used to characterise both the crystalline and the freshly prepared glass and to monitor the extent of relaxation at temperatures below the glass transition (Tg). No ageing occurred at 35, 40 and 45 °C at the measured lengths of times. Molecular relaxation time constants (τKWW) for samples aged at 65, 75 and 85 °C were determined by the Kohlrausch-Williams-Watts (KWW) equation. The fragility parameter m (a measure of the stability below the glass transition) was determined from the Tg dependence from the cooling and heating rates, and IND was found to be relatively stable ("moderately fragile") in the amorphous state. Temperature-modulated DSC was used to separate reversing and nonreversing processes for unaged amorphous IND. The enthalpy relaxation peak was clearly observed as a part of the nonreversing signal. Heat capacities data for unaged and physically aged IND were fitted to Cp baselines of solid and liquid states of IND, were integrated and enthalpy was presented as a function of temperature.

Onium salts improve the kinetics of photopolymerization of acrylate activated with visible light.

The aim was study the influence of onium salts on the kinetics of photopolymerization in the visible light region. Trimethylolpropane triacrylate TMPTA was selected as a monomer, and activated by 1,3-bis(phenylamino)squaraine (SQ) used as a photosensitizer in addition to tetramethylammonium n-butyltriphenylborate (B2). The iodonium salt [A-I-B]+X- functioned as a second radical initiator, bearing a different substitution pattern for the cation. The ternary system was formulated with different concentrations of both borate and diphenyliodonium salts. Differential scanning calorimetry was used to investigate the polymerization reaction over the photoactivation time carried out at 300 nm < λ < 500 nm irradiation. When the squaraine dye/borate salt was used as photoinitiator, a slow polymerization reaction was observed and a lower monomer conversion. The addition of a third component (onium salt) increased the polymerization rate and conversion. Ternary photoinitiator systems showed improvement in the polymerization rate of triacrylate leading to high conversion in a short photoactivation time. The photoinitiating ability of bi- and tri-component photoinitiators acting in the UV-Vis region for initiation polymerization of triacrylate was compared with those of some commercially used photoinitiating systems. It was also found, that, the parallel electron transfer from an excited state of the sensitizer to [A-I-B]+X-, and an electron transfer from a ground state of R(Ph)3B-N(CH3)4 + to an excited state of the sensitizer results in two types of initiating radical.

Influence of the Nature of the Amino Group in Highly Fluorescent Difluoroborates Exhibiting Intramolecular Charge Transfer.

A series of difluoroborates were synthesized from CH acids. All compounds were substituted with dialkylamino groups (NR2). The lone electron pair of the nitrogen atom of this donor moiety is variably delocalized toward the difluoroborate core that acts as the electron acceptor. This was rationalized in light of the various geometries of the amino group. The degree of charge transfer was quantified on the basis of the results of time-dependent density functional theory calculations.

Synthesis and structural characterization of substituted 2-phenacylbenzoxazoles.

1H and 13C NMR spectra of eleven 2-phenacylbenzoxazoles (ketimine form) show that their CDCl(3)-solutions contains also (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimine form). Intramolecular hydrogen bonding in the latter tautomer was found to be significantly weaker than that one in respective (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines. Integrals of the 1H NMR signals were used to evaluate the molar ratio of the tautomers. Strong electron-donating substituents were found to stabilize the ketimine tautomer. pK(T) (negative logarithm of the equilibrium constant, K(T) = [ketimine]/[enolimine]) was found to be linearly dependent on the Hammett substituent constant σ. The results of the MP2 ab initio calculations reveal enolimine including an intramolecular OH…N hydrogen bond to be the most stable form both with electron-donor and electron-acceptor substituents. The stability of ketimines is an intermediate of those found for enolimines and enaminones i.e., (E)-2-(benzo[d]oxazol-2(3H)-ylidene)-1-phenylethanones. 13C CPMAS NMR spectral data reveal that in the crystalline state the ketimine tautomer is predominant in p-NMe(2) substituted congener. On the other hand, enolimine forms were detected there when the substituent has less electron-donating character or when it is an electron-acceptor by character.

2-Methyl-4-phenyl-3,4-dihydro-quinazoline.

The title compound, C(15)H(14)N(2), was formed during the lithia-tion of 2-methyl-quinazoline with phenyl-lithium followed by hydrolysis of the inter-mediate lithium 2-methyl-4-phenyl-4H-quinazolin-3-ide. NMR spectra as well as single-crystal X-ray structural data indicate that the reaction product to have the same structure in chloro-form solution as in the crystalline state. The phenyl substituent is twisted out of the plane of the 3,4-dihydro-quinazoline ring system by 86.47 (7)°. In the crystal, inter-molecular N-H⋯N inter-actions connect the mol-ecules into infinite chains.

Instability of 2,2-di(pyridin-2-yl)acetic acid. Tautomerization versus decarboxylation.

The DFT calculations at the B3LYP level with 6-311G** basis set were carried out in order to reveal whether tautomerization or decarboxylation is responsible for the instability of 2,2-di(pyridin-2-yl)acetic (DPA) and 1,8-diazafluorene-9-carboxylic (DAF) acids. The carboxyl protons in both compounds are involved in the intramolecular hydrogen bonds (the pyridine nitrogen atoms are the hydrogen bond acceptors). Although formation of two intramolecular OH · · · N hydrogen bonds in the enols of both carboxylic acids enables effective electron delocalization within the quasi rings (· · · HO - C = C - C = N), only ene-1,1-diol of DAF has somewhat lower energy than DAF itself (ΔE is ca. 7 kcal mol(-1)). DPA and its enediol have comparable energies. Migration of the methine proton toward the carbonyl oxygen atom (to form enediols) requires overstepping the energy barriers of 55-57 kcal mol(-1) for both DPA and DAF. The enaminone tautomers of the acids, formed by migration of this proton toward the pyridine nitrogen atom, are thermodynamically somewhat more stable than the respective enediols. The energy barriers of these processes are equal to ca. 44 and 62 kcal mol(-1) for DPA and DAF, respectively. Thus, such tautomerization of the acids is not likely to proceed. On the other hand, the distinct energetic effects (ca. 15 kcal mol(-1)) favor decarboxylation. This process involves formation of (E)-2-(pyridin-2(1H)-ylidenemethyl)pyridine and its cyclic analogue followed by their tautomerization to (dipyridin-2-yl)methane and 1,8-diazafluorene, respectively. Although the later compound was found to be somewhat thermodynamically more stable, kinetic control of tautomerization of the former is more distinct.