Lara C. Spencer

Cobalt analogs of Ru-based water oxidation catalysts: overcoming thermodynamic instability and kinetic lability to achieve electrocatalytic O2 evolution

Several binuclear cobalt(III) complexes that mimic Ru-based water oxidation catalysts have been prepared. The initial complexes exhibited thermodynamic instability and kinetic lability that complicated efforts to use these cobalt complexes as electrocatalysts for water oxidation. Binuclear cobalt(III) complexes supported by a bridging bispyridylpyrazolate (bpp) ligand overcome these limitations. Two bpp-ligated dicobalt(III)-peroxo complexes were prepared and structurally characterized, and electrochemical investigation of these complexes supports their ability to serve as molecular electrocatalysts for water oxidation under acidic conditions (pH 2.1).

Characteristic Structural Parameters for the γ-Peptide 14-Helix:Importance of Subunit Preorganization

We report crystallographic data for a set of homologous γ-peptides that contain a Boc-protected residue derived from the flexible gabapentin monomer at the N-terminus and cyclically constrained γ-residues at all other positions. The crystallized γ-peptides range in length from 3 to 7 residues. Previously only one atomic-resolution structure had been available for a short γ-peptide 14-helix. The new data provided here allow derivation of characteristic parameters for the γ-peptide 14-helix, and establish guidelines for characterizing 14-helical folding in solution via 2D NMR. In addition, the results suggest that the substitution pattern of a γ-residue has a profound effect on the propensity for 14-helical folding.

New Preorganized γ-Amino Acids as Foldamer Building Blocks

An asymmetric synthesis of two new diastereomeric γ-amino acids is described. Both molecules contain a cyclohexyl ring to limit conformational flexibility about the Cα-Cβ bond; they differ in having cis vs trans stereochemistry on the ring. Residues derived from the cis γ isomer are shown to support helical secondary structures in α/γ-peptide oligomers.

Crystallographic characterization of 12-helical secondary structure in β-peptides containing side chain groups.

Helices are the most extensively studied secondary structures formed by β-peptide foldamers. Among the five known β-peptide helices, the 12-helix is particularly interesting because the internal hydrogen bond orientation and macrodipole are analogous to those of α-peptide helices (α-helix and 3(10)-helix). The β-peptide 12-helix is defined by i, i+3 C═O···H-N backbone hydrogen bonds and promoted by β-residues with a five-membered ring constraint. The 12-helical scaffold has been used to generate β-peptides with specific biological functions, for which diverse side chains must be properly placed along the backbone and, upon folding, properly arranged in space. Only two crystal structures of 12-helical β-peptides have previously been reported, both for homooligomers of trans-2-aminocyclopentanecarboxylic acid (ACPC). Here we report five additional crystal structures of 12-helical β-peptides, all containing residues that bear side chains. Four of the crystallized β-peptides include trans-4,4-dimethyl-2-aminocyclopentanecarboxylic acid (dm-ACPC) residues, and the fifth contains a β(3)-hPhe residue. These five β-peptides adopt fully folded 12-helical conformations in the solid state. The new crystal structures, along with previously reported data, allow a detailed characterization of the 12-helical conformation; average backbone torsion angles of β-residues and helical parameters are derived. These structural parameters are found to be similar to those for i, i+3 C═O···H-N hydrogen-bonded helices formed by other peptide backbones generated from α- and/or β-amino acids. The similarity between the conformational behavior of dm-ACPC and ACPC is consistent with previous NMR-based conclusions that 4,4-disubstituted ACPC derivatives are compatible with 12-helical folding. In addition, our data show how a β(3)-residue is accommodated in the 12-helix, thus enhancing understanding of the diverse conformational behavior of this flexible class of β-amino acids.

A γ-amino acid that favors 12/10-helical secondary structure in α/γ-peptides.

H-bonded helices in conventional peptides (containing exclusively homochiral α-amino acid residues) feature a uniform H-bonding directionality, N-terminal side C═O to C-terminal side NH. In contrast, heterochiral α-peptides can form helices in which the H-bond directionality alternates along the backbone because neighboring amide groups are oriented in opposite directions. Alternating H-bond directions are seen also in helices formed by unnatural peptidic backbones, e.g., those containing β- or γ-amino acid residues. In the present study, we used NMR spectroscopy and crystallography to evaluate the conformational preferences of the novel γ-amino acid (1R,2R,3S)-2-(1-aminopropyl)-cyclohexanecarboxylic acid (APCH), which is constrained by a six-membered ring across its Cα-Cβ bond. These studies were made possible by the development of a stereoselective synthesis of N-protected APCH. APCH strongly enforces the α/γ-peptide 12/10-helical secondary structure, which features alternating H-bond directionality. Thus, APCH residues appear to have a conformational propensity distinct from those of other cyclically constrained γ-amino acid residues.

Constructor graph description of the hydrogen-bonding supramolecular assembly in two ionic compounds: 2-(pyrazol-1-yl)ethylammonium chloride and diaquadichloridobis(2-hydroxyethylammonium)cobalt(II) dichloride.

Covalent bond tables are used to generate hydrogen-bond pattern designator symbols for the crystallographically characterized title compounds. 2-(Pyrazol-1-yl)ethylammonium chloride, C(5)H(10)N(3)(+).Cl(-), (I), has three unique, strong, charge-assisted hydrogen bonds of the types N-H...Cl and N-H...N that form unary through ternary levels of graph-set interactions. Diaquadichloridobis(2-hydroxyethylammonium)cobalt(II) dichloride, [CoCl(2)(C(2)H(8)NO)(2)(H(2)O)(2)]Cl(2), (II), forms five unique charge-assisted hydrogen bonds of the types O-H...Cl and N-H...Cl. These form graph-set patterns up to the quinary level. The Co complex in (II) resides at a crystallographic inversion center; thus the number of hydrogen bonds to consider doubles due to their G-equivalence, and the handling of such a case is demonstrated.

Haptotropic rearrangement in tricarbonylchromium complexes of 2-aminobiphenyl and 4-aminobiphenyl.

The para-aminobiphenyl compound [(η(6)-C(6)H(5))(C(6)H(4)-4-NH(2))]Cr(CO)(3) (1) has an arene-phenyl dihedral angle of 38.01(6)°, as determined by single-crystal X-ray crystallography, and 34.7(11)°, as determined by DFT calculations. It undergoes haptotropic rearrangement at 140 °C in solution to form [(η(6)-C(6)H(4)-4-NH(2))(C(6)H(5))]Cr(CO)(3) (2), even though previous reports have suggested that such rearrangements should not be observed in compounds with arene-phenyl dihedral angles greater than 22°. NMR analysis gave a rate constant of k = 5.0 × 10(-5) s(-1) for the rearrangement of 1 to 2. The ortho-substituted analog [(η(6)-C(6)H(5))(C(6)H(4)-2-NH(2))]Cr(CO)(3) (3) has an arene-phenyl dihedral angle of 67.70(7)°, as determined by single-crystal X-ray crystallography, and 51.9(10)°, as determined by DFT calculations. Surprisingly, even though it displays a more extreme canting of arene rings, 3 rearranges to [(η(6)-C(6)H(4)-2-NH(2))(C(6)H(5))]Cr(CO)(3) (4) at 140 °C in solution with a rate constant of k = 2.6 × 10(-4) s(-1). This approximately five-fold rate enhancement likely results from the ortho-amino group providing intramolecular stabilization for intermediates formed during the rearrangement.

Polymorphism of 5-(pyridin-2-ylmethylene)-3-phenyl-2-methylthio-3,5-dihydro-4H-imidazole-4-one

The title compound, C16H13N3OS (1), exists in three polymorphic forms. Crystalline 1 undergoes an enantiotropic, first-order, k2 phase transition at 262.9(5) K with ΔH = 0.3(1) kJ mol−1. Upon cooling below the transition temperature, the high temperature orthorhombic polymorph (Form I, space groupPbcm) transforms into a low temperature orthorhombic polymorph (Form II, space groupPbca) with a unit cell twice the size of that of the Form I. A molten 1 can be cooled in a controlled fashion to generate a monoclinic Form III of 1 with the unit cell size similar to that of Form I. Metastable Form III, once isolated, is indefinitely stable between 100 K and its melting point of 466 K. If crystals of Form III are in contact with seed crystals of Form I, a monotropic t2 first-order Form III → Form I phase transition occurs upon heating with the onset between 420 and 448 K and ΔH = −1.7(4) kJ mol−1. The most substantial differences among the molecular geometries of 1 in Forms I–III are observed in the position and tilt of the phenyl ring relative to the rest of the molecule. The packing in Form III is very different from those in the other polymorphs. DFT molecular geometry optimizations produce the following order of stable molecule configurations: Form II (most stable), Form I (0.50 kJ mol−1), Form III (2.81 kJ mol−1).

Constructor graph description of hydrogen bonding in a supramolecular assembly of (3,5-dimethyl-1H-pyrazol-4-ylmethyl)isopropylammonium chloride monohydrate

Five distinct strong hydrogen-bonding interactions of four kinds (N-H...Cl, N-H...O, O-H...N, and O-H...Cl) connect molecules of the title compound, C(9)H(18)N(3)(+).Cl(-).H(2)O, in the crystal structure into corrugated sheets stacked along the a axis. The intermolecular interactions are efficiently described in terms of the first- through fifth-level graph sets. A two-dimensional constructor graph helps visualize the supramolecular assembly.

5′,11′-Dihydro­dispiro­[cyclo­hexane-1,6′-indolo[3,2-b]carbazole-12′,1′′-cyclo­hexa­ne]

The title compound, C28H30N2, is a symmetrical 2:2 product from the condensation of indole and cyclohexanone. It is the only reported 5,11-dihydroindolo[3,2-b]carbazole compound in which the spiro atoms are quaternary C atoms. Crystals were grown by vapor diffusion in a three-zone electric furnace. The molecule resides on a crystallographic inversion center. The cyclohexyl rings are in a slightly distorted chair conformation, whereas the indole units and the spiro-carbons are coplanar within 0.014 Å.