Fine Tunable,Redox Active Octapalladium Chains Supported by Linear Tetraphosphines,Leading to Dynamically 1D Self-Assembled Coordination Polymers

A series of the octapalladium chains supported by meso-Ph₂PCH₂P(Ph)CH₂P(Ph)CH₂PPh₂ (meso-dpmppm) ligands, [Pd₈(meso-dpmppm)₄(L)₂](BF₄)₄ (L=none ( 1 ), solvents: CH₃CN ( 2 a ), dmf ( 2 b ), dmso ( 2 c ), RN≡C: R=Xyl ( 3 a ), Mes ( 3 b ), Dip ( 3 c ), ^tBu ( 3 d ), Cy ( 3 e ), CH₃(CH₂)₇ ( 3 f ), CH₃(CH₂)₁₁ ( 3 g ), CH₃(CH₂)₁₇ ( 3 h )) and [Pd₈(meso-dpmppm)₄(X)₂](BF₄)₂ (X=Cl ( 4 a ), N₃ ( 4 b ), CN ( 4 c ), SCN ( 4 d )), were synthesized by using 2 a as a stable good precursor, and characterized by spectroscopic (IR, ¹H and ³¹P NMR, UV-vis-NIR, ESI-MS) measurements and X-ray crystallographic analyses (for 1 , 2 a , b , 3 a , b , e , f , 4 a – d ). On the basis of DFT calculations on the X-ray determined structure of 2 b ( [2b-Pd₈]⁴⁺ ) and the optimized models [Pd₈(meso-Ph₂PCH₂P(H)CH₂P(H)CH₂PH₂)₄(CH₃CN)₂]⁴⁺ ( [Pd₈Ph₈]⁴⁺ ) and [Pd₈(meso-H₂PCH₂P(H)CH₂P(H)CH₂PH₂)₄(CH₃CN)₂]⁴⁺ ( [Pd₈H₈]⁴⁺ ), with and without empirically calculating dispersion force stabilization energy (B3LYP-D3, B3LYP), the formation energy between the two Pd₄ fragments is assumed to involve mainly noncovalent interactions (ca. −70 kcal/mol) with four sets of interligand C−H/π interactions and Pd⋅⋅⋅Pd metallophilic one, while electron shared covalent interactions are almost canceled out within the Pd₈ chain. All the compounds isolated are stable in solution and exhibit characteristic absorption at ∼900 nm, which is assignable to a spin allowed HOMO to LUMO transition, and shows temperature dependent intensity change with variable absorption coefficients presumably due to coupling with some thermal vibrations. The structures and electronic states of the Pd₈ chains are found finely tunable by varying the terminal capping ligands. In particular, theoretical calculations elucidated that the HOMO-LUMO energy gap is systematically related to the central Pd−Pd distance (2.7319(6)–2.7575(6) Å) by two ways with neutral ligands L ( 1 , 2 , 3 ) and with anionic ligands X ( 4 ), which are reflected on the NIR absorption energy of 867–954 nm. The isocyanide terminated Pd₈ complexes ( 3 ) further reacted with excess of RNC (6 eq) to afford the Pd₄ complexes, [Pd₄(meso-dpmppm)₂(RNC)₂](BF₄)₂ ( 13 ), and the cyclic voltammograms of 2 a (L=CH₃CN), 3 , and 13 (R=Xyl, Mes, ^tBu, Cy) demonstrated wide range redox behaviors from 2{Pd₄}⁴⁺ to 2{Pd₄}⁰ through 2{Pd₄}²⁺↔{Pd₈}⁴⁺, {Pd₈}³⁺, and {Pd₈}²⁺ strings. The oxidized complexes, [Pd₄(meso-dpmppm)₂(RNC)₃](BF₄)₄ ( 16 ), were characterized by X-ray analyses, and the two-electron reduced chain of [Pd₈(meso-dpmppm)₄](BF₄)₂ ( 7 ) was analyzed by spectroscopic and electrochemical techniques and DFT calculations. Reactions of 2 a with 1 equiv. of aromatic linear bisisocyanide (BI) in CH₂Cl₂ deposited insoluble coordination polymers, {[Pd₈(meso-dpmppm)₄(BI)](BF₄)₄}_n ( 5 ), and interestingly, they were soluble in acetonitrile, ³¹P{¹H} and ¹H DOSY NMR spectra as well as SAXS curves suggesting that the coordination polymers may exist in acetonitrile as dynamically 1D self-assembled coordination polymers comprising ca. 50 units of the Pd₈ rod averaged within the timescale.     

In Vitro Analyses of Spinach-Derived Opioid Peptides,Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and β-Arrestin-Mediated Pathways

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKey^TM assay, cADDis^® cAMP assay, and PathHunter^® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKey^TM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis^® cAMP and PathHunter^® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.     

Crystal Structures of Mono-, Di-, and Tri(p-tert-butyl)-thiacalix[4]arenes: Dimeric Self-inclusion Behavior

X-Ray crystal structures of the mono-, di-, and tri(p-tert-butyl)-substituted thiacalix[4]arenes (TC4As; 1, 2, and 3, respectively) have beendetermined. TC4As 1–3 adopt a cone conformation and form dimeric self-inclusion units in such a manner that phenol moieties are inserted into the cavity of each molecule. In all the crystal structures of 1–3, lateralface-to-face interactions exist between the phenol rings that do not bear a tert-butyl substituent, and seemingly, this molecular assembly stabilizes the formation of self-inclusion. TC4As 1 and 2 adopt a cone conformation with C₂ symmetry, leading to the formation of rim-to-rim intermolecular hydrogenbonds so as to link the dimeric units up and down. On the other hand, 3 adopts a regular cone conformation with C₄ symmetry to form cyclic hydrogen bonds withinthe rim part of TC4A.     

Synthesis and Properties of Polycarbosilanes Having Lactose‐Derived Structures

A polycarbosilane having lactose‐derived structures was synthesized, and its thermal property, cytotoxicity, chemical crosslinking, and protein adsorption properties were investigated. The polycarbosilane (PSB‐Lac) was prepared by a thiol‐ene reaction between precursor poly(1‐(3‐butenyl)‐1‐methylsilacyclubane) (PSB) and heptaacetyl lactose that carried a thiol group at the anomeric position, and the successive deprotection of the acetyl groups. The lactose introduction efficiency determined by ¹H NMR measurement was 75%. TGA and DSC revealed that the polymer had a 5 wt% decomposition temperature of 260 °C and glass transition temperature (T_g) of 84 °C, which indicated that PSB‐Lac was a thermally stable polymer. PSB‐Lac had no significant cytotoxicity, which was evaluated by human liver cancer cell line HepG2 cultivation on the polystyrene dishes coated with the polymer. Urethane‐crosslinked PSB‐Lac films were prepared by casting solutions of PSB‐Lac and hexamethylene diisocyanate and heating at 120 °C after evaporation of the solvent. The crosslinked PSB‐Lac showed higher adsorption of bovine serum albumin than the similarly crosslinked polycarbosilane that had a glucose structure (PSB‐Glc). © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2420–2425     

Preconcentration of copper, cadmium, and lead with a thiacalix[4]arenetetrasulfonate-loaded Sephadex A-25 anion-exchanger for graphite-furnace atomic-absorption spectrometry

A rapid column-adsorption method has been developed for concentrating traces of copper, cadmium, and lead in water prior to their determinations by graphite-furnace atomic-absorption spectrometry. The adsorbent used was prepared by loading a strongly basic anion-exchanger QAE-Sephadex A-25 (50 mg) with thiacalix[4]arenetetrasulfonate (20 mol). Two-hundredfold preconcentration of the analyte elements was achieved by passing 100 mL of sample solution (pH 8.0) through a column packed with the adsorbent (6 mm i.d.×7 mm high) at a flow rate of 10 mL min^–1 and by the subsequent elution with 500 L of aqueous nitric acid solution (1 mol L^–1). The practical applicability of the proposed method was evaluated by analyzing certified reference seawater samples.     

Synthetic studies on the taxane skeleton: construction of eight-membered carbocyclic rings by the intramolecular B-alkyl Suzuki-Miyaura cross-coupling reaction

Construction of eight-membered carbocyclic rings via the intramolecular B-alkyl Suzuki-Miyaura cross-coupling reaction has been studied. This protocol proved its potency through the formation of the eight-membered ring possessing a quaternary carbon on its ring in high yield, affording promise of a new access to the eight-membered ring of Taxol. [reaction: see text]     

Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2

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Highlights? CPYPP binds to DOCK2 DHR-2 domain and inhibits its catalytic activity ? CPYPP inhibits DOCK2-mediated Rac activation in cells ? The structural features of CPYPP required for its inhibitory effect were revealed ? CPYPP inhibits lymphocyte migration and activation in vitro and in vivo     

Application of 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate in the synthesis of 7a-substituted hexahydro-1h-pyrrolizines

The method for preparing 7a-substituted hexahydro-1H-pyrrolizines 2 from 1,2,3,5,6,7-hexahydropyrrol-izinium Perchlorate (3) was investigated, by which introduction of a wide variety of functionalities on C(7a) could be achieved easily.     

Amino acids and peptides. XIII. Synthetic studies on N-terminal tripeptide amide analogs of fibrin alpha-chain

N-Terminal tripeptide analogs of fibrin alpha-chain were synthesized and their inhibitory effect on fibrinogen/thrombin clotting was examined. A new water-soluble active ester, 3-pyridinium ester, was used for the synthesis. Among the synthetic peptides, H-Gly-Pro-Arg-hexamethyleneimine exhibited the highest inhibitory effect on fibrinogen-thrombin clotting.     

Formation of pyrazine derivatives from D-glucosamine and their deoxyribonucleic acid (DNA) strand breakage activity

Two pyrazine derivatives [fructosazine (3) and deoxyfructosazine (6)] were simultaneously formed in a solution of D-glucosamine hydrochloride under various conditions. They showed deoxyribonucleic acid (DNA) strand breakage activity in plasmid pBR322 comparable to that of D-glucosamine. The DNA strand breakage by fructosazine (3) was stimulated by Cu2+.