Интеграция науки, образования, права и этики в сфере генной, клеточной и тканевой биоветтехнологии

The paper analyzes the reasons of necessity in constant improving of ethic and legal space of educational and scientific activity in the modern world. The analysis is based on applying of new investigations in the field of biotechnology. The paper reveals problems appeared when studying reproduction and regeneration mechanisms. The authors demonstrate specific procedure of biological science development and enlighten the problems of interaction between “new possibilities” and archaic conditions contributing to their implementation. Problems of “new consciousness” and old views about human place in the world are shown as well. The article explains that gnosis dialectics of living matter leads to revolutions which demand strong changes in the life of modern society; when the modern society turns into society of knowledge and innovations and changes the subject of this process.В статье анализируются причины необходимости перманентного совершенствования этико-правового пространства образовательной и научной деятельности современного человека на примере новых направлений биотехнологии, а также освещаются проблемы изучения механизмов репродукции и регенерации. Показана специфика развития биологических наук, освещены проблемы взаимодействия «новых возможностей» и архаичных условий для их реализации, проблемы «нового сознания» и старых представлений о месте человека в мире. Обосновано, что диалектика познания живой материи неизбежно проводит к формированию революционных ситуаций, требующих кардинальных перемен в жизни современного информационного общества, превращения его в общество знаний и инноваций с соответствующим изменением субъекта этого процесса

Phosphine-NHC-Phosphonium Ylide Pincer Ligand: Complexation with Pd(II) and Unconventional P-Coordination of the Ylide Moiety

An efficient synthesis of two pincer pre-ligands [Ph2PCH(R)ImCH2CH2CH2PPh3]X2 (R = H, X = OTf; R = Ph, X = BF4) was developed. Subsequent reactions with PdCl2 and an excess of Cs2CO3 lead to the formation of highly stable cationic orthometalated Pd(II) complexes [(P,C,C,C)Pd]X exhibiting phosphine, NHC, phosphonium ylide and σ-aryl donor extremities. The protonation of one of the latter complexes with R = H affords the Pd(II) complex [(P,C,C)Pd(MeCN)](OTf)2 bearing an unprecedented nonsymmetrical NHC core pincer scaffold with a 5,6-chelating framework. The overall donor properties of this phosphine-NHCphosphonium ylide ligand were estimated using experimental nCN stretching frequency in the corresponding [(P,C,C)Pd(CNtBu](OTf)2 derivative and was shown to be competitive with related bis(NHC)-phosphonium ylide and phenoxy-NHC-phosphonium ylide pincers. The presence of a phenyl substituent in the bridge between phosphine and NHC moieties in orthometalated complex [(P,C,C,C)Pd](BF4) makes possible the deprotonation of this position using LDA to provide a persistent zwitterionic complex [(P,C,C,C)Pd] featuring a rare P-coordinated phosphonium ylide moiety in addition to a conventional C-coordinated one. The comparison of the 31P and 13C NMR data for these C- and P-bound phosphonium ylide fragments within the same molecule was performed for the first time and the bonding situation in both cases was studied in detail by QTAIM and ELF topological analyses

Two active species from a single metal halide precursor: a case study of highly productive Mn-catalyzed dehydrogenation of amine-boranes via intermolecular bimetallic cooperation

International audienceMetal–metal cooperation for inert bond activation is a ubiquitous concept in coordination chemistry and catalysis. While the great majority of such transformations proceed via intramolecular mode in binuclear complexes, to date only a few examples of intermolecular small molecule activation using usually bimetallic frustrated Lewis pairs (Mδ+⋯M′δ−) have been reported. We introduce herein an alternative approach for the intermolecular bimetallic cooperativity observed in the catalytic dehydrogenation of amine-boranes, in which the concomitant activation of N–H and B–H bonds of the substrate via the synergetic action of Lewis acidic (M+) and basic hydride (M–H) metal species derived from the same mononuclear complex (M–Br). It was also demonstrated that this system generated in situ from the air-stable Mn(I) complex fac-[(CO)3(bis(NHC))MnBr] and NaBPh4 shows high activity for H2 production from several substrates (Me2NHBH3, tBuNH2BH3, MeNH2BH3, NH3BH3) at low catalyst loading (0.1% to 50 ppm), providing outstanding efficiency for Me2NHBH3 (TON up to 18 200) that is largely superior to all known 3d-, s-, p-, f-block metal derivatives and frustrated Lewis pairs (FLPs). These results represent a step forward towards more extensive use of intermolecular bimetallic cooperation concepts in modern homogeneous catalysis

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to “positive regulation of tumor necrosis factor biosynthetic process”, “cell adhesion”, “TNF signaling pathway”, and “phagosome” as compared with non-responding ones. In contrast, positive and negative “regulation of cell proliferation” and “HIF-1 signaling pathway” mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia

The Dichotomy of Mn–H Bond Cleavage and Kinetic Hydricity of Tricarbonyl Manganese Hydride Complexes

Acid-base characteristics (acidity, pKa, and hydricity, ΔG°H− or kH−) of metal hydride complexes could be a helpful value for forecasting their activity in various catalytic reactions. Polarity of the M–H bond may change radically at the stage of formation of a non-covalent adduct with an acidic/basic partner. This stage is responsible for subsequent hydrogen ion (hydride or proton) transfer. Here, the reaction of tricarbonyl manganese hydrides mer,trans–[L2Mn(CO)3H] (1; L = P(OPh)3, 2; L = PPh3) and fac–[(L–L′)Mn(CO)3H] (3, L–L′ = Ph2PCH2PPh2 (dppm); 4, L–L′ = Ph2PCH2–NHC) with organic bases and Lewis acid (B(C6F5)3) was explored by spectroscopic (IR, NMR) methods to find the conditions for the Mn–H bond repolarization. Complex 1, bearing phosphite ligands, features acidic properties (pKa 21.3) but can serve also as a hydride donor (ΔG≠298K = 19.8 kcal/mol). Complex 3 with pronounced hydride character can be deprotonated with KHMDS at the CH2–bridge position in THF and at the Mn–H position in MeCN. The kinetic hydricity of manganese complexes 1–4 increases in the order mer,trans–[(P(OPh)3)2Mn(CO)3H] (1) mer,trans–[(PPh3)2Mn(CO)3H] (2) ≈ fac–[(dppm)Mn(CO)3H] (3) fac–[(Ph2PCH2NHC)Mn(CO)3H] (4), corresponding to the gain of the phosphorus ligand electron-donor properties

Impact of the Methylene Bridge Substitution in Chelating NHC‐Phosphine Mn(I) Catalyst for Ketone Hydrogenation

International audienceSystematic modification of the chelating NHC‐phosphine ligand (NHC = N ‐heterocyclic carbene) in highly efficient ketone hydrogenation Mn(I) catalyst fac ‐[(Ph 2 PCH 2 NHC)Mn(CO) 3 Br] has been performed and the catalytic activity of the resulting complexes was evaluated using acetophenone as a benchmark substrate. While the variation of phosphine and NHC moieties led to inferior results than for a parent system, the incorporation of a phenyl substituent into the ligand methylene bridge improved catalytic performance by ca . 3 times providing maximal TON values in the range of 15000–20000. Mechanistic investigation combining experimental and computational studies allowed to rationalize this beneficial effect as an enhanced stabilization of reaction intermediates including anionic hydride species fac ‐[(Ph 2 PC(Ph)NHC)Mn(CO) 3 H] − playing a crucial role in the hydrogenation process. These results highlight the interest of such carbon bridge substitution strategy being rarely employed in the design of chemically non‐innocent ligands

Dihydrogen Bond Intermediated Alcoholysis of Dimethylamine–Borane in Nonaqueous Media

Dimethylamine–borane (DMAB) acid/base properties, its dihydrogen-bonded (DHB) complexes and proton transfer reaction in nonaqueous media were investigated both experimentally (IR, UV/vis, NMR, and X-ray) and theoretically (DFT, NBO, QTAIM, and NCI). The effects of DMAB concentration, solvents polarity and temperature on the degree of DMAB self-association are shown and the enthalpy of association is determined experimentally for the first time (−Δ<i>H</i>°_assoc = 1.5–2.3 kcal/mol). The first case of “improper” (blue-shifting) NH···F hydrogen bonds was observed in fluorobenzene and perfluorobenzene solutions. It was shown that hydrogen-bonded complexes are the intermediates of proton transfer from alcohols and phenols to DMAB. The reaction mechanism was examined computationally taking into account the coordinating properties of the reaction media. The values of the rate constants of proton transfer from HFIP to DMAB in acetone were determined experimentally [(7.9 ± 0.1) × 10^–4 to (1.6 ± 0.1) × 10^–3 mol^–1·s^–1] at 270–310 K. Computed activation barrier of this reaction Δ<i>G</i>^‡theor_298 K(acetone) = 23.8 kcal/mol is in good agreement with the experimental value of the activation free energy Δ<i>G</i>^‡exp_270 K = 21.1 kcal/mol

Unusual Tri‑, Hexa‑, and Nonanuclear Cu(II) Cage Methylsilsesquioxanes: Synthesis, Structures, and Catalytic Activity in Oxidations with Peroxides

Three types of unusual cagelike copper­(II) methylsilsesquioxanes, namely, nona- [(MeSiO_1.5)₁₈(CuO)₉] <b>1</b>, hexa- [(MeSiO_1.5)₁₀(HO_0.5)₂(CuO)₆­​(C₁₂H₈N₂)₂­(MeSiO_1.5)₁₀(HO_0.5)_1.33­​(CH₃COO_0.5)_0.67(CuO)₆­(C₁₂H₈N₂)₂] <b>2</b>, [(MeSiO_1.5)₁₀(CuO)₆­​(MeO_0.5)₂­(C₁₀H₈N₂)₂] <b>3</b>, and trinuclear [(MeSiO_1.5)₈­​(CuO)₃(C₁₀H₈N₂)₂] <b>4</b>, were obtained in 44%, 27%, 20%, and 16% yields, respectively. Nuclearity and structural fashion of products was controlled by the choice of solvent system and ligand, specifically assisting the assembling of cage. Structures of <b>1</b>–<b>4</b> were determined by single-crystal X-ray diffraction analysis. Compounds <b>1</b> and <b>4</b> are the first cage metallasilsesquioxanes, containing nine and three Cu ions, respectively. Product <b>1</b> is the first observation of nonanuclear metallasilsesquioxane ever. Unique architecture of <b>4</b> represents early unknown type of molecular geometry, based on two condensed pentamembered siloxane cycles. Topological analysis of metal clusters in products <b>1</b>–<b>4</b> is provided. Complex <b>1</b> efficiently catalyzes oxidation of alcohols with <i>tert</i>-butylhydroperoxide TBHP to ketones or alkanes with H₂O₂ to alkyl hydroperoxides in acetonitrile