Understanding the nature of the intermediate species operating within a palladium catalytic cycle is crucial for developing efficient cross-coupling reactions. Even though the XPhos/Pd(OAc)2 catalytic system has found numerous applications, the nature of the active catalytic species remains elusive. A Pd0 complex ligated to XPhos has been detected and characterized in situ for the first time using cyclic voltammetry and NMR techniques. In the presence of XPhos, Pd(OAc)2 initially associates with the ligand to form a complex in solution, which has been characterized as PdII (OAc)2 (XPhos). This PdII center is then reduced to the Pd0 (XPhos)2 species by an intramolecular process. This study also sheds light on the formation of PdI -PdI dimers. Finally, a kinetic study probes a dissociative mechanism for the oxidative addition with aryl halides involving Pd0 (XPhos) as the reactive species in equilibrium with the unreactive Pd0 (XPhos)2 . Remarkably, the reportedly poorly reactive PhCl reacts at room temperature in the oxidative addition, which confirms the crucial role of the XPhos ligand in the activation of aryl chlorides.

Formation of XPhos-Ligated Palladium(0) Complexes and Reactivity in Oxidative Additions.

一系列 3 代用品 quinazolinones， 2 代用品 quinoxalines 和 2 代用品 benzopyrans 在 vitro 为他们的抗真菌的活动被综合并且评估。在 vitro 优秀的揭示的新混合物有宽广光谱的抗真菌的活动。衍生物的结构活动关系(SAR ) 被分析。复合 9A2 比 fluconazole 在 vitro 对 5 测试真菌展出更好抗真菌的活动，特别对 Trichophyton rubrum 和 Microsporum gypseum。这研究为 non-azole 的发展提供一系列新奇的铅混合物抗真菌的代理人。

Design,synthesis and biological evaluation of novel non-azole derivatives as potential antifungal agents

Evaluation of the genotoxic and antigenotoxic potential of lignin-derivative BP-C2 in the comet assay in vivo.

The role of the enzyme-modified comet assay in in vivo studies.

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily primed PCR to analyze their intrinsic DNA damage-inducing and DNA methylation-changing abilities. We demonstrate that small modifications in the substitution patterns of carbazoles can have profound effects on their intrinsic genotoxic and epigenetic properties, with PK9320 and PK9323 being eligible candidates as "anticancer compounds" and "anticancer epi-compounds" and PK083 a "damage-corrective" compound on human breast adenocarcinoma cells. Such different properties may be exploited for their use as anticancer agents and chemical probes.

https://www.mdpi.com/1422-0067/22/7/3410/pdf

Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells.

The class of carbazoles includes compounds with high biological activities and broad spectra of action. PLX01107 and PLX01008 are xenomycins, a new subclass of antimicrobial carbazole derivatives demonstrating strong antifungal activity in vitro. We performed three tests, a bacterial reverse mutation assay (Ames test), in vitro cytokinesis-block micronucleus assay, and chromosome aberration test in mouse bone marrow cells, to investigate the possible genotoxicity of these compounds. Despite their structural similarity, the two compounds had different genotoxicity profiles. PLX01008 showed positive effects in all assays. PLX01107 showed no mutagenicity in the Ames test but demonstrated strong cytogenetic activity in vitro and in vivo. PLX01107 was also tested in the in vivo alkaline comet assay, where a weak but statistically significant increase in DNA damage was seen in liver cells 24h after treatment. Significantly increased levels of formamidopyrimidine DNA glycosylase (FPG)-sensitive sites were found in bone marrow cells of PLX01107-treated mice (FPG-modified comet assay), suggesting induction of oxidative or alkylation damage to DNA.

Genotoxicity of two new carbazole derivatives with antifungal activity.

The feasibility of soft mechanochemical synthesis was studied here for hydroxyapatite with various types of substitution. It was shown that this method allows obtaining hydroxyapatites substituted with copper or iron cations and hydroxyapatites cosubstituted with zinc cations and silicate groups. Thermal stability of the synthesized samples was evaluated. It was found that to preserve phase homogeneity of the material, the temperature during the preparation of ceramic products and coatings should not exceed 600–800 °C. An exception is the hydroxyapatite where a hydroxyl group is expected to be replaced by a copper cation during the synthesis at a degree of substitution x = 0.5. For this sample, the temperature of the the heat treatment can be increased to 1100–1200 °C because copper cations return to the hydroxyapatite crystal lattice at these temperatures, and the material becomes single-phase.

/pdf/soft-mechanochemical-synthesis-and-thermal-stability-of-20oyigds.pdf

Soft mechanochemical synthesis and thermal stability of hydroxyapatites with different types of substitution

The doping of hydroxyapatite with various substituent ions can give this material new and useful properties. Nonetheless, local distortions of structure after doping can change the properties of the material. In this work, the thermal stability of copper-substituted hydroxyapatite synthesized by the mechanochemical method was investigated. In situ diffraction analyses showed that copper ion diffusion during the heating of Cu-substituted hydroxyapatite promotes phase transformations in the substituted hydroxyapatite. The behavior of copper ions was studied in samples with ratios (Ca + Cu)/P = 1.75 and 1.67. It was found that in both cases, single-phase Cu-substituted hydroxyapatite with the general formula Ca10−xCux(PO4)6−y(CO3)y(OH)2−yOy is formed by the mechanochemical synthesis. When heated at approximately 600–700 °C, the lattice loses copper cations, but at higher temperatures, CuO diffusion into the hydroxyl channel takes place. Cuprate-substituted hydroxyapatite with the general formula Ca10(PO4)6(OH)2−2x(CuO2)x forms in this context. At 1200 °C, the sample is single-phase at (Ca + Cu)/P = 1.75. Nonetheless, slow cooling of the material leads to the emergence of a CuO phase, as in the case of (Ca + Cu)/P = 1.67, where the material contains not only CuO but also Cu-substituted tricalcium phosphate. In the manufacture of ceramic products from Cu-substituted hydroxyapatite, these structural transformations must be taken into account, as they alter not only thermal but also biological properties of such materials.

/pdf/diffusion-of-copper-ions-in-the-lattice-of-substituted-35zj24qh.pdf

Diffusion of Copper Ions in the Lattice of Substituted Hydroxyapatite during Heat Treatment

This paper considers studies aimed at identifying markers of genotoxicity (chromosomal aberrations, micronuclei, and DNA damage assessed by the DNA comet assay) in patients with both gestational diabetes mellitus (GDM) and diabetes type 1 and 2 (T1DM and T2DM, respectively), as well as possible changes in the levels of these genotoxic markers under the influence of medicines and nutritions. Patients with T2DM are characterized by an increased level of genotoxicity markers. The results of genotoxicity markers in patients with T1DM and GDM studies are contradictory, however, they indicate the presence of an increased genotoxic load rather than its absence. The levels of genotoxic damage in diabetic patients may be reduced by physical exercises, diet, and/or hypoglycemic drugs. Metformin, Afobazole and Noopept are recommended for experimental and clinical studies as possible drug candidates that reduce the levels of genotoxic biomarkers in diabetic patients.

Genotoxic markers in patients with diabetes mellitus (Literature review)

The analysis of experimental data on the study of the genotoxic activity of psychotropic drugs published over the past 25 years has been carried out. It has been shown that the information describing the genotoxicity of psychotropic drugs is characterized by fragmentation, contradictions, and the conditions for their experimental production often do not meet modern requirements. Conclusions about the presence or absence of genotoxic properties can be made only for 9.6% 94 examined drugs. The need for a large-scale systematic reassessment of the genotoxicity of psychotropic drugs, especially drugs of the first generation, on the basis of modern methodology, including studies of mutagen-modifying activity, has been proven. The expediency of monitoring the genotoxic status of patients receiving psychotropic drugs is emphasized, which should contribute to an adequate assessment of the genotoxic risk of their use and objectification of approaches when choosing a drug for the safe therapy. The urgency of conducting research to determine the role of primary DNA damage in the pathogenesis of mental illnesses has been substantiated.

Natalya V. Eremina

Papers

Genotoxicity of two new carbazole derivatives with antifungal activity.

Soft mechanochemical synthesis and thermal stability of hydroxyapatites with different types of substitution

Diffusion of Copper Ions in the Lattice of Substituted Hydroxyapatite during Heat Treatment

Genotoxic markers in patients with diabetes mellitus (Literature review)

[Genotoxicity of psychotropic drugs in experimental and clinical studies].