X-ray crystal structures of intermediates (1<i>S</i>,3<i>R</i>,4<i>R</i>)-11 and <i>rac</i>-11 are shown above as displacement ellipsoid drawings (50%).

<p>The positional disorder of the benzyl group in <b><i>rac</i></b><b>-11</b> is shown as lighter lines. Hydrogen atoms are omitted for clarity. Structural depiction of the stereochemistries of <b>(1</b><b><i>S</i></b><b>,3</b><b><i>R</i></b><b>,4</b><b><i>R</i></b><b>)-11</b> and <b><i>rac</i></b><b>-11</b> are shown below each crystal structure.</p

Pin1 inhibitors discussed are cyclohexyl ketones 1 and <i>rac</i>-2 (this work); reduced amides 3 and 4 [<b>27</b>]; (<i>Z</i>)-alkene 5 [<b>13</b>]; and α-ketoamides 6a and 6b [<b>14</b>].

<p>Pin1 inhibitors discussed are cyclohexyl ketones 1 and <i>rac</i>-2 (this work); reduced amides 3 and 4 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Xu3" target="_blank">[<b>27</b>]</a>; (<i>Z</i>)-alkene 5 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Zhao1" target="_blank">[<b>13</b>]</a>; and α-ketoamides 6a and 6b <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Xu2" target="_blank">[<b>14</b>]</a>.</p

Viologen-Based Rotaxanes from Dibenzo-30-crown-10

Three [2]­rotaxanes (<b>4</b>, <b>7</b>, and <b>12</b>) and one [3]­rotaxane (<b>8</b>) were synthesized based on the dibenzo-30-crown-10/viologen binding motif. To the best of our knowledge, these are the first rotaxanes formed from dibenzo-30-crown-10 and viologens. The rotaxanes were all characterized by ¹H NMR, ¹³C NMR, and HRMS. An X-ray crystal structure of one of the [2]­rotaxanes (<b>7</b>) was obtained. This work demonstrates for the first time that dibenzo-30-crown-10 does form pseudorotaxane complexes with viologens in solution

Pin1 is proposed to stretch the prolyl ring by binding phosphate and C-terminal residues tightly, creating a <i>trans</i>-pyrrolidine conformation of the substrate and forcing pyramidalization of the prolyl nitrogen in the twisted-amide mechanism.

<p>Distance measurements are from calculated structures of Ac–Pro–OH in the ground state and the <i>trans</i>-pyrrolidine transition state.</p

Models of cyclohexyl ketone inhibitors were docked with dynamic minimization.

<p>(A) <b>(1</b><b><i>S,</i></b><b>3</b><b><i>R,</i></b><b>4</b><b><i>R</i></b><b>)-1</b> in orange, (B) <b>(1</b><b><i>R,</i></b><b>3</b><b><i>R,</i></b><b>4</b><b><i>R</i></b><b>)-2</b> in blue, (C) <b>(1</b><b><i>S,</i></b><b>3</b><b><i>S,</i></b><b>4</b><b><i>S</i></b><b>)-2</b> in green, and (D) superposition of all atoms of <b>1</b> and <b><i>rac</i></b><b>-2</b>. Models were based on PDB 2Q5A <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Zhang2" target="_blank">[32]</a>, and minimized using Sybyl 8.1.1 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-1" target="_blank">[42]</a>. Images were prepared using MacPyMol <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-DeLano1" target="_blank">[44]</a>.</p

Viologen-Based Rotaxanes from Dibenzo-30-crown-10

Three [2]­rotaxanes (<b>4</b>, <b>7</b>, and <b>12</b>) and one [3]­rotaxane (<b>8</b>) were synthesized based on the dibenzo-30-crown-10/viologen binding motif. To the best of our knowledge, these are the first rotaxanes formed from dibenzo-30-crown-10 and viologens. The rotaxanes were all characterized by ¹H NMR, ¹³C NMR, and HRMS. An X-ray crystal structure of one of the [2]­rotaxanes (<b>7</b>) was obtained. This work demonstrates for the first time that dibenzo-30-crown-10 does form pseudorotaxane complexes with viologens in solution

Ketone inhibitors were designed to mimic the tetrahedral intermediate of proposed mechanism B.

<p>(A) Proposed Pin1 hydrogen-bond assisted twisted amide mechanism <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Schroeder1" target="_blank">[25]</a>, (B) Pin1 Cys113 nucleophilic-addition mechanism tetrahedral intermediate proposed by Ranganathan et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044226#pone.0044226-Ranganathan1" target="_blank">[26]</a>. (C) Electrophilic ketone inhibitor designed to mimic the proposed tetrahedral intermediate upon Cys113-S nucleophilic addition.</p

Regio- and Chemoselective Diboration of Allenes with Unsymmetrical Diboron: Formation of Vinyl and Allyl Boronic Acid Derivatives

A platinum-catalyzed terminal diboration of 1,1-disubstituted allenes using a differentially protected diboron is described. Diboration occurs in a regio- and chemoselective fashion to furnish vinyl and allyl boronates in good to excellent yield and selectivity. Transformation of the bis-boronyl products to other functional groups as well as in chemoselective cross-coupling is demonstrated

High-Yielding Syntheses of Crown Ether-Based Pyridyl Cryptands

Pyridinium bis­(trifluoromethylsulfonyl)­imide (PyTFSI)-templated syntheses of 2,6-pyridyl cryptands of <i>cis</i>(4,4′)-dibenzo-30-crown-10 (<b>3a</b>), the <i>p-</i>bromobenzyloxy derivative <b>3b</b>, bis­(<i>m</i>-phenylene)-32-crown-10 (<b>5</b>), <i>cis</i>(4,4′)-dibenzo-27S-crown-9 (<b>7</b>), <i>cis</i>(4,4′)-dibenzo-27L-crown-9 (<b>9</b>), and <i>cis</i>(4,4′)-dibenzo-24-crown-8 (<b>11</b>) are reported. Here we provide a fast (12 h), high-yielding (89%, 74%, 80%, and 62% for <b>3a</b>, <b>3b</b>, <b>5</b>, and <b>9</b>, respectively) templation method without the use of a syringe pump. The yields for <b>7</b> (19%) and <b>11</b> (26%) were lower than with the previous pseudo-high-dilution method, indicating ineffective templation in these cases. Coupled with our previously developed templated syntheses of dibenzo crown ethers, this protocol makes powerful cryptand hosts readily available in gram quantities in good yields from methyl 4­(or 3)-hydroxy-3­(or 4)-benzyloxybenzoate

Relative Mechanical Strengths of Weak Bonds in Sonochemical Polymer Mechanochemistry

The mechanical strength of scissile chemical bonds plays a role in material failure and in the mechanical activation of latent reactivity, but quantitative measures of mechanical strength are rare. Here, we report the relative mechanical strength of polymers bearing three putatively “weak” scissile bonds: the carbon–nitrogen bond of an azobisdialkylnitrile (<30 kcal mol^–1), the carbon–sulfur bond of a thioether (71–74 kcal mol^–1), and the carbon–oxygen bond of a benzylphenyl ether (52–54 kcal mol^–1). The mechanical strengths are assessed in the context of chain scission triggered by pulsed sonication of polymer solutions, by using two complementary techniques: (i) the competition within a single polymer chain between the bond scission of interest and the nonscissile mechanochemical ring opening of <i>gem</i>-dichlorocyclopropane mechanophores and (ii) the molecular weights at long (4 h) sonication times of multimechanophore polymers. The two methods produce a consistent story: in contrast to their thermodynamic strengths, the relative mechanical strengths of the three weak bonds are azobisdialkylnitrile (weakest) < thioether < benzylphenyl ether. The greater mechanical strength of the benzylphenyl ether relative to the thermodynamically stronger carbon–sulfur bond is ascribed to poor mechanochemical coupling, at least in part as a result of the rehybridization that accompanies carbon–oxygen bond scission