Homogeneous and Robust Polyproline Type I Helices from Peptoids with Nonaromatic α‑Chiral Side Chains

Peptoids that are oligomers of <i>N</i>-substituted glycines represent a class of peptide mimics with great potential in areas ranging from medicinal chemistry to biomaterial science. Controlling the equilibria between the <i>cis</i> and <i>trans</i> conformations of their backbone amides is the major hurdle to overcome for the construction of discrete folded structures, particularly for the development of all-<i>cis</i> polyproline type I (PPI) helices, as tools for modulating biological functions. The prominent role of backbone to side chain electronic interactions (<i>n</i> → π*) and side chains bulkiness in promoting <i>cis</i>-amides was essentially investigated with peptoid aromatic side chains, among which the chiral 1-naphthylethyl (<i>1npe</i>) group yielded the best results. We have explored for the first time the possibility to achieve similar performances with a sterically hindered α-chiral aliphatic side chain. Herein, we report on the synthesis and detailed conformational analysis of a series of (<i>S</i>)-<i>N</i>-(1-<i>tert</i>-butylethyl)­glycine (<i>N</i>s1tbe) peptoid homo-oligomers. The X-ray crystal structure of an <i>N</i>s1tbe pentamer revealed an all-<i>cis</i> PPI helix, and the CD curves of the <i>N</i>s1tbe oligomers also resemble those of PPI peptide helices. Interestingly, the CD data reported here are the first for any conformationally homogeneous helical peptoids containing only α-chiral aliphatic side chains. Finally we also synthesized and analyzed two mixed oligomers composed of <i>Nt</i>Bu and <i>N</i>s1tbe monomers. Strikingly, the solid state structure of the mixed oligomer Ac-(<i>t</i>Bu)₂-(<i>s1tbe</i>)₄-(<i>t</i>Bu)₂-COO<i>t</i>Bu, the longest to be solved for any linear peptoid, revealed a PPI helix of great regularity despite the presence of only 50% of chiral side chain in the sequence

Time-Resolved Assembly of Chiral Uranyl Peroxo Cage Clusters Containing Belts of Polyhedra

Two chiral cage clusters built from uranyl polyhedra and (HPO₃)^2– groups have been synthesized in pure yield and characterized structurally and spectroscopically in the solid state and aqueous solution. Synthesis reactions under ambient conditions in mildly acidic aqueous solutions gave clusters <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ that contain belts of four uranyl peroxide pentagonal and hexagonal bipyramids, in contrast to earlier reported uranyl peroxide cage clusters that are built from four-, five-, and six-membered rings of uranyl hexagonal bipyramids. <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ are also the first chiral uranyl-based cage clusters, the first that contain uranyl pentagonal bipyramids that contain no peroxide ligands, and the first that incorporate (HPO₃)^2– bridges between uranyl ions. They are built from 22 uranyl polyhedra and 20 (HPO₃)^2– groups, or 28 uranyl polyhedra and 24 (HPO₃)^2– groups, with the outer and inner surfaces of the cages passivated by the O atoms of uranyl ions. Small-angle X-ray scattering (SAXS) profiles demonstrated that <i>U</i>₂₂<i>PO</i>₃ clusters formed in solution within 1 h after mixing of reactants, and remained in solution for 2 weeks prior to crystallization. Time-resolved electrospray ionization mass spectrometry and SAXS demonstrated that <i>U</i>₂₈<i>PO</i>₃ clusters formed in solution within 1 h of mixing the reactants, and remained in solution 1 month before crystallization. Crystallization of <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ is accelerated by addition of KNO₃. Clusters of <i>U</i>₂₂<i>PO</i>₃ with and without encapsulated cations exhibit markedly different aqueous solubility, reflecting the importance of cluster surface charge in fostering linkages through counterions to form a stable solid

Time-Resolved Assembly of Chiral Uranyl Peroxo Cage Clusters Containing Belts of Polyhedra

Two chiral cage clusters built from uranyl polyhedra and (HPO₃)^2– groups have been synthesized in pure yield and characterized structurally and spectroscopically in the solid state and aqueous solution. Synthesis reactions under ambient conditions in mildly acidic aqueous solutions gave clusters <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ that contain belts of four uranyl peroxide pentagonal and hexagonal bipyramids, in contrast to earlier reported uranyl peroxide cage clusters that are built from four-, five-, and six-membered rings of uranyl hexagonal bipyramids. <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ are also the first chiral uranyl-based cage clusters, the first that contain uranyl pentagonal bipyramids that contain no peroxide ligands, and the first that incorporate (HPO₃)^2– bridges between uranyl ions. They are built from 22 uranyl polyhedra and 20 (HPO₃)^2– groups, or 28 uranyl polyhedra and 24 (HPO₃)^2– groups, with the outer and inner surfaces of the cages passivated by the O atoms of uranyl ions. Small-angle X-ray scattering (SAXS) profiles demonstrated that <i>U</i>₂₂<i>PO</i>₃ clusters formed in solution within 1 h after mixing of reactants, and remained in solution for 2 weeks prior to crystallization. Time-resolved electrospray ionization mass spectrometry and SAXS demonstrated that <i>U</i>₂₈<i>PO</i>₃ clusters formed in solution within 1 h of mixing the reactants, and remained in solution 1 month before crystallization. Crystallization of <i>U</i>₂₂<i>PO</i>₃ and <i>U</i>₂₈<i>PO</i>₃ is accelerated by addition of KNO₃. Clusters of <i>U</i>₂₂<i>PO</i>₃ with and without encapsulated cations exhibit markedly different aqueous solubility, reflecting the importance of cluster surface charge in fostering linkages through counterions to form a stable solid

Cation Templating and Electronic Structure Effects in Uranyl Cage Clusters Probed by the Isolation of Peroxide-Bridged Uranyl Dimers

The self-assembly of uranyl peroxide polyhedra into a rich family of nanoscale cage clusters is thought to be favored by cation templating effects and the pliability of the intrinsically bent U–O₂–U dihedral angle. Herein, the importance of ligand and cationic effects on the U–O₂–U dihedral angle were explored by studying a family of peroxide-bridged dimers of uranyl polyhedra. Four chemically distinct peroxide-bridged uranyl dimers were isolated that contain combinations of pyridine-2,6-dicarboxylate, picolinate, acetate, and oxalate as coordinating ligands. These dimers were synthesized with a variety of counterions, resulting in the crystallographic characterization of 15 different uranyl dimer compounds containing 17 symmetrically distinct dimers. Eleven of the dimers have U–O₂–U dihedral angles in the expected range from 134.0 to 156.3°; however, six have 180° U–O₂–U dihedral angles, the first time this has been observed for peroxide-bridged uranyl dimers. The influence of crystal packing, countercation linkages, and π–π stacking impact the dihedral angle. Density functional theory calculations indicate that the ligand does not alter the electronic structure of these systems and that the U–O₂–U bridge is highly pliable. Less than 3 kcal·mol^–1 is required to bend the U–O₂–U bridge from its minimum energy configuration to a dihedral angle of 180°. These results suggest that the energetic advantage of bending the U–O₂–U dihedral angle of a peroxide-bridged uranyl dimer is at most a modest factor in favor of cage cluster formation. The role of counterions in stabilizing the formation of rings of uranyl ions, and ultimately their assembly into clusters, is at least as important as the energetic advantage of a bent U–O₂–U interaction

Exploring the Conformation of Mixed <i>Cis</i>–<i>Trans</i> α,β-Oligopeptoids: A Joint Experimental and Computational Study

The synthesis and conformational preferences of a set of new synthetic foldamers that combine both the α,β-peptoid backbone and side chains that alternately promote <i>cis</i>- and <i>trans</i>-amide bond geometries have been achieved and addressed jointly by experiment and molecular modeling. Four sequence patterns were thus designed and referred to as <i>cis</i>-β-<i>trans</i>-α, <i>cis</i>-α-<i>trans</i>-β, <i>trans</i>-β-<i>cis</i>-α, and <i>trans</i>-α-<i>cis</i>-β. α- and β<i>Nt</i>Bu monomers were used to enforce <i>cis</i>-amide bond geometries and α- and β<i>N</i>Ph monomers to promote <i>trans</i>-amides. NOESY and molecular modeling reveal that the <i>trans</i>-α-<i>cis</i>-β and <i>cis</i>-β-<i>trans</i>-α tetramers show a similar pattern of intramolecular weak interactions. The same holds for the <i>cis</i>-α-<i>trans</i>-β and <i>trans</i>-β-<i>cis</i>-α tetramers, but the interactions are different in nature than those identified in the <i>trans</i>-α-<i>cis</i>-β-based oligomers. Interestingly, the <i>trans</i>-α-<i>cis</i>-β peptoid architecture allows establishment of a larger amount of structure-stabilizing intramolecular interactions

Exploring the Conformation of Mixed <i>Cis</i>–<i>Trans</i> α,β-Oligopeptoids: A Joint Experimental and Computational Study

The synthesis and conformational preferences of a set of new synthetic foldamers that combine both the α,β-peptoid backbone and side chains that alternately promote <i>cis</i>- and <i>trans</i>-amide bond geometries have been achieved and addressed jointly by experiment and molecular modeling. Four sequence patterns were thus designed and referred to as <i>cis</i>-β-<i>trans</i>-α, <i>cis</i>-α-<i>trans</i>-β, <i>trans</i>-β-<i>cis</i>-α, and <i>trans</i>-α-<i>cis</i>-β. α- and β<i>Nt</i>Bu monomers were used to enforce <i>cis</i>-amide bond geometries and α- and β<i>N</i>Ph monomers to promote <i>trans</i>-amides. NOESY and molecular modeling reveal that the <i>trans</i>-α-<i>cis</i>-β and <i>cis</i>-β-<i>trans</i>-α tetramers show a similar pattern of intramolecular weak interactions. The same holds for the <i>cis</i>-α-<i>trans</i>-β and <i>trans</i>-β-<i>cis</i>-α tetramers, but the interactions are different in nature than those identified in the <i>trans</i>-α-<i>cis</i>-β-based oligomers. Interestingly, the <i>trans</i>-α-<i>cis</i>-β peptoid architecture allows establishment of a larger amount of structure-stabilizing intramolecular interactions

Evidence of New Fluorinated Coordination Compounds in the Composition Space Diagram of FeF₃/ZnF₂–H<i>amtetraz</i>-HF_aq System

The exploration of the composition space diagram of the FeF₃/ZnF₂–H<i>amtetraz</i>-HF_aq system (H<i>amtetraz</i> = 5-aminotetrazole) by solvothermal synthesis at 160 °C for 72 h in dimethylformamide (DMF) has evidenced five new hybrid fluorides (<b>1</b>–<b>5</b>); the structures are characterized from single crystal X-ray diffraction data. [H<i>dma</i>]­·(ZnFe^III(H₂O)₄F₆) (<b>1</b>) and [H<i>dma</i>]­·[H<i>gua</i>]₂­·(Fe^IIIF₆) (<b>2</b>) contain anionic inorganic chains (<b>1</b>) or isolated octahedra (<b>2</b>) weakly hydrogen bonded (Class I hybrids) to dimethylammonium (H<i>dma</i>) and/or guanidinium (H<i>gua</i>) cations which are produced from the tetrazole ligand and solvent decomposition. [H<i>dma</i>]₂­·[H<i>gua</i>]­·[NH₄]­·[ZnFe^IIIF₅(<i>amtetraz</i>)₂]₂ (<b>3</b>), [H<i>dma</i>]₂­·[Zn_1.6Fe^II_0.4Fe^IIIF₆­(<i>amtetraz</i>)₃] (<b>4</b>), and [H<i>dma</i>]­·[Zn₄F₅(<i>amtetraz</i>)₄] (<b>5</b>) are considered as Class II hybrids in which the (<i>amtetraz</i>)⁻ anions are strongly linked to divalent metal cations via N–M bonds. In <b>3</b>, _∞{[NH₄]­·[ZnFe^IIIF₅­(<i>amtetraz</i>)₂]₂} layers are separated by [H<i>dma</i>]⁺ and [H<i>gua</i>]⁺ cations. <b>4</b> and <b>5</b> exhibit three-dimensional (3D) hybrid networks that contain small cavities where [H<i>dma</i>]⁺ cations are inserted. A porous 3D metal–organic framework intermediate is evidenced from the thermogravimetric analysis and X-ray thermodiffraction of <b>5</b>