De novo design of a redox-active minimal rubredoxin mimic

Metal-binding sites in metalloproteins frequently occur at the interfaces of elements of secondary structure, which has enabled the retrostructural analysis of natural proteins and the de novo design of helical bundles that bind metal ion cofactors. However, the design of metalloproteins containing beta-structure is less well developed, despite the frequent occurrence of beta-conformations in natural metalloproteins. Here, we describe the design and construction of a beta-protein, RM1, that forms a stable, redox-active 4-Cys thiolate Fe(II/III) site analogous to the active site of rubredoxin. The protein folds into a beta-structure in the presence and absence of metal ions and binds Fe(II/III) to form a redox-active site that is stable to repeated cycles of oxidation and reduction, even in an aerobic environment.     

A Puckered Singlet Cyclopentane‐1,3‐diyl: Detection of the Third Isomer in Homolysis

In the photochemical denitrogenation of 1,4‐diaryl‐2,3‐diazabicyclo[2.2.1]heptane ( AZ6 ) bearing sterically hindered substituents, a curious new absorption band at about 450 nm was observed under low‐temperature matrix conditions, together with the previously well‐characterized planar singlet diradical pl‐¹ DR6 with λ_max=≈580 nm. The 450 nm species was electron paramagnetic resonance (EPR)‐silent. Instead of generating the planar diradical pl‐¹ DR6 and the precursor azoalkane AZ6 upon warming, the ring‐closed bicyclo[2.1.0]pentane derivative SB6 , that is, the AZ6 denitrogenation product was identified. Based on product analysis, low‐temperature spectroscopic observations, high‐level quantum‐mechanical computations, viscosity effect, and laser‐flash photolysis, the puckered singlet diradicaloid puc‐¹ DR6 was assigned to the new 450 nm absorption. The latter was detected experimentally at the same time as the planar singlet diradical pl‐¹ DR6 . Sterically demanding substituents as well as viscosity impediments were essential for the detection of the experimentally hitherto unknown puckered singlet cyclopentane‐1,3‐diyl diradicaloid puc‐¹ DR6 , that is, the third isomer in homolysis. The present findings should stimulate future work on the mechanistically fascinating stereoselectivity documented in the formation of bicyclo[2.1.0]pentanes during the 2,3‐diazabicyclo[2.2.1]heptane denitrogenation.     

Activation of stable polymeric esters by using organo‐activated acyl transfer reactions

In this study, we succeeded in the in situ activation of nonactivated ester moieties embedded in polymer structures. Although poly(pentafluorophenyl methacrylate) (PPFPMA) can react with 2‐ethylhexylamine at 50 °C in the presence of proton scavenger such as NEt₃, such conditions were not suitable for poly(phenyl methacrylate) (PPhMA). Nevertheless, the combination of organo‐activating agents, namely 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) and 1,2,4‐triazole (TZ) led to a facile conversion from ester to amide for PPhMA. The reaction between PPhMA and 2‐ethylhexylamine was conducted at 120 °C in the presence of one equivalent of TZ and three equivalents of DBU and yielded >99% ester conversion to afford corresponding polymethacrylamide derivatives as confirmed by FT‐IR and ¹H NMR measurements. In addition, poly(2,2,2‐trifluoroethyl methacrylate) (PTFEMA) and poly(methyl methacrylate) (PMMA) were also allowed to react with amines in the presence of the organo‐activating agents with dramatically increased conversions (>70%). © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1353–1358     

Palladium-Catalyzed Decarboxylative Alkynylation of α-Acyloxyketones by C(sp3)−O Bond Cleavage

Palladium-catalyzed decarboxylative alkynylation of α-acyloxyketones triggered by C(sp³)−O bond cleavage is disclosed. The decarboxylation strategy featuring a neutral reaction condition enabled an unprecedent catalytic alkynylation of a ketone enolate. The reaction was applied to a variety of substrates, giving desired products in good yields. We successfully obtained X-ray crystallography of a new palladium–enolate intermediate that was synthesized by a reaction of [Pd(cod)(CH₂TMS)₂] with XPhos and α-acyloxyketone at room temperature, indicating facile C(sp³)−O bond disconnection.     

A screw-shaped alignment of pyrene using m-calix[3]amide

m-Calix[3]amide bearing three pyrenes (1a) was prepared by the condensation reaction of 3-nonylaminobenzoic acid derivative using Ph₃PCl₂. Pyrenyl groups were found to be aligned in the screw-like fashion by m-calix[3]amide as confirmed by the X-ray crystallography. Aromatic proton signals observed at the up-field region in the ¹H NMR spectrum at low temperature indicated that pyrenyl groups in 1a are aligned in close proximity in THF solution. UV–vis absorption and fluorescence emission spectra did not show marked peak shift nor concentration fluorescence quenching compared with reference compounds implying no significant electronic interaction between pyrenyl groups. These results can be explained by the steric effect of the m-calix[3]amide platform. On the other hand, an excimer emission was observed for m-calix[3]amide having a flexible spacer between pyrene and m-calix[3]amide (1b).     

Synthesis and properties of thermotropic liquid-crystalline polyesters containing 9,10-diphenylanthracene moiety in the main chain

We synthesized thermotropic liquid-crystalline polyesters in which 9,10-diphenylanthracene moieties are incorporated into the main chain type of polyester forming the chiral smectic C (Sm C*). The polymers were prepared by the isopropyltitanate-catalyzed reaction of biphenyldicarboxylic acid and the corresponding diols, with different ratios of diol of 9,10-diphenylanthracene moiety to the alkane diols (1, 5, and 10 mol %) under nitrogen atmosphere. The polymers exhibited thermotropic liquid crystals despite the presence of a bulky diphenylanthracene moiety in the main chain. The circular dichroism spectra revealed that a Sm C* phase was formed in the polymer with 1 mol % of anthracene moiety, although only an Sm A phase was formed in the other polymers. This is the first example of a Sm C* polyester containing a diphenylanthracene moiety in the main chain. Furthermore, we measured the optical properties of the polymers and found that they exhibited very high fluorescent efficiency. The fluorescence spectra of the thin film differed from that of a CH₂Cl₂ solution.     

Ni‐Catalyzed [4+3+2] Cycloaddition of Ethyl Cyclopropylideneacetate and Dienynes: Scope and Mechanistic Insights

A detailed study of the Ni‐catalyzed [4+3+2] cycloaddition reaction between ethyl cyclopropylideneacetate and dienynes has been conducted, resulting in the development of a new method for the synthesis of compounds containing nine‐membered rings. We studied the reactivity of various dienynes, together with their substituent and conformational effects. The mechanism of the reaction was probed by examining the stoichiometric reactions of the Ni complexes and dienynes.     

Adaptive lambda square dynamics simulation: An efficient conformational sampling method for biomolecules

A novel, efficient sampling method for biomolecules is proposed. The partial multicanonical molecular dynamics (McMD) was recently developed as a method that improved generalized ensemble (GE) methods to focus sampling only on a part of a system (GEPS); however, it was not tested well. We found that partial McMD did not work well for polylysine decapeptide and gave significantly worse sampling efficiency than a conventional GE. Herein, we elucidate the fundamental reason for this and propose a novel GEPS, adaptive lambda square dynamics (ALSD), which can resolve the problem faced when using partial McMD. We demonstrate that ALSD greatly increases the sampling efficiency over a conventional GE. We believe that ALSD is an effective method and is applicable to the conformational sampling of larger and more complicated biomolecule systems. © 2013 Wiley Periodicals, Inc.     

Multiple Reaction Pathways Operating in the Mechanism of Vinylogous Mannich‐Type Reaction Activated by a Water Molecule

A systematic search for reaction pathways for the vinylogous Mannich‐type reaction was performed by the artificial force induced reaction method. This reaction affords δ‐amino‐γ‐butenolide in one pot by mixing 2‐trimethylsiloxyfuran, imine, and water under solvent‐free conditions. Surprisingly, the search identified as many as five working pathways. Among them, two concertedly produce anti and syn isomers of the product. Another two give an intermediate, which is a regioisomer of the main product. This intermediate can undergo a retro‐Mannich reaction to give a pair of intermediates: an imine and 2‐furanol. The remaining pathway directly generates this intermediate pair. The imine and 2‐furanol easily react with each other to afford the product. Thus, all of these stepwise pathways finally converge to give the main product. The rate‐determining step of all five (two concerted and three stepwise) pathways have a common mechanism: concerted Si? O bond formation through the nucleophilic attack of a water molecule on the silicon atom followed by proton transfer from the water molecule to the imine. Therefore, these five pathways have comparable barriers and compete with each other.