The d'--d--d' vertical triad is less discriminating than the a'--a--a' vertical triad in the antiparallel coiled-coil dimer motif

Elucidating relationships between the amino-acid sequences of proteins and their three-dimensional structures, and uncovering non-covalent interactions that underlie polypeptide folding, are major goals in protein science. One approach toward these goals is to study interactions between selected residues, or among constellations of residues, in small folding motifs. The α-helical coiled coil has served as a platform for such studies because this folding unit is relatively simple in terms of both sequence and structure. Amino acid side chains at the helix-helix interface of a coiled coil participate in so-called "knobs-into-holes" (KIH) packing whereby a side chain (the knob) on one helix inserts into a space (the hole) generated by four side chains on a partner helix. The vast majority of sequence-stability studies on coiled-coil dimers have focused on lateral interactions within these KIH arrangements, for example, between an a position on one helix and an a' position of the partner in a parallel coiled-coil dimer, or between a--d' pairs in an antiparallel dimer. More recently, it has been shown that vertical triads (specifically, a'--a--a' triads) in antiparallel dimers exert a significant impact on pairing preferences. This observation provides impetus for analysis of other complex networks of side-chain interactions at the helix-helix interface. Here, we describe a combination of experimental and bioinformatics studies that show that d'--d--d' triads have much less impact on pairing preference than do a'--a--a' triads in a small, designed antiparallel coiled-coil dimer. However, the influence of the d'--d--d' triad depends on the lateral a'--d interaction. Taken together, these results strengthen the emerging understanding that simple pairwise interactions are not sufficient to describe side-chain interactions and overall stability in antiparallel coiled-coil dimers; higher-order interactions must be considered as well.     

Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids

Electron spin-echo envelope modulation (ESEEM) spectroscopy of phospholipids spin-labeled systematically down the sn-2 chain was used to detect the penetration of water (D2O) into bilayer membranes of dipalmitoyl phosphatidylcholine with and without 50 mol % cholesterol. Three-pulse stimulated echoes allow the resolution of two superimposed 2H-ESEEM spectral components of different widths, for spin labels located in the upper part of the lipid chains. Quantum chemical calculations (DFT) and ESEEM simulations assign the broad spectral component to one or two D2O molecules that are directly hydrogen bonded to the N-O group of the spin label. Classical ESEEM simulations establish that the narrow spectral component arises from nonbonded water (D2O) molecules that are free in the hydrocarbon chain region of the bilayer membrane. The amplitudes of the broad 2H-ESEEM spectral component correlate directly with those of the narrow component for spin labels at different positions down the lipid chain, reflecting the local H-bonding equilibria. The D2O-ESEEM amplitudes decrease with position down the chain toward the bilayer center, displaying a sigmoidal dependence on position that is characteristic of transmembrane polarity profiles established by other less direct spin-labeling methods. The midpoint of the sigmoidal profile is shifted toward the membrane center for membranes without cholesterol, relative to those with cholesterol, and the D2O-ESEEM amplitude in the outer regions of the chain is greater in the presence of cholesterol than in its absence. For both membrane types, the D2O amplitude is almost vanishingly small at the bilayer center. The water-penetration profiles reverse correlate with the lipid-chain packing density, as reflected by 1H-ESEEM intensities from protons of the membrane matrix. An analysis of the H-bonding equilibria provides essential information on the binding of water molecules to H-bond acceptors within the hydrophobic interior of membranes. For membranes containing cholesterol, approximately 40% of the nitroxides in the region adjacent to the lipid headgroups are H bonded to water, of which ca. 15% are doubly H bonded. Corresponding H-bonded populations in membranes without cholesterol are ca. 20%, of which ca. 6% are doubly bonded.     

Comparison of model predictions with measured proton-induced production of nickel and iridium isotopes

Journal of Radioanalytical and Nuclear Chemistry - Calculations were performed to support method development for simultaneous production of Ni and Ir isotopes. The work scope included development...     

Synthesis and conformational studies of palladium(II) complexes containing [PhP(O)NP(E)Ph]− (E=S or Se)

The ligands [Ph₂P(O)NP(E)Ph₂]⁻ (E=S I; E=Se II) can readily be complexed to a range of palladium(II) starting materials affording new six-membered Pd–O–P–N–P–E palladacycles. Hence ligand substitution reaction of the chloride complexes [PdCl₂(bipy)] (bipy=2,2′-bipyridine), [{Pd(μ-Cl)(L–L)}₂] (HL–L=C₉H₁₃N or C₁₂H₁₃N), [{Pd(μ-Cl)Cl(PMe₂Ph)}₂] or [PdCl₂(PR₃)₂] [PR₃=PPh₃; 2PR₃=Ph₂PCH₂CH₂PPh₂or cis-Ph₂PCH=CHPPh₂] with either I (or II) in thf or CH₃OH gave [Pd{Ph₂P(O)NP(E)Ph₂-O,E}(bipy)]PF₆, [Pd{Ph₂P(O)NP(E)Ph₂-O,E}(L–L)], [Pd{Ph₂P(O)NP(E)Ph₂-O,E}Cl(PMe₂Ph)] or [Pd{Ph₂P(O)NP(E)Ph₂-O,E} (PR₃)₂]PF₆ in good yields. All compounds described have been characterised by a combination of multinuclear NMR [31 P{1 H} and 1 H] and IR spectroscopy and microanalysis. The molecular structures of five complexes containing the selenium ligand II have been determined by single-crystal X-ray crystallography. Three different ring conformations were observed, a pseudo-butterfly, hinge and in the case of all three PR₃ complexes, pseudo-boat conformations. Within the Pd–O–P–N–P–Se rings there is evidence for π-electron delocalisation.     

Chiral aminocyclopentene-based cycloaddition strategies to bicyclic [3.3.0] rings

Two cycloaddition methods were applied to chiral protected aminocyclopentenes 2 and 9 and provided novel bicyclic products 3 and 4 in good yields. The explanation for the observed stereochemistry was based on the sterically encumbered β-face forcing the cycloadditions to occur on the α-face of the cyclopentene ring. The stereochemistry of 4 was confirmed by X-ray of the fumarate salt 10 and showed the trans-relationship between the newly formed ring and the chiral –NHBoc group.     

Estimation of the surface sulfur content of cellulose nanocrystals prepared by sulfuric acid hydrolysis

The conditions required for the accurate measurement of the sulfur content of cellulose nanocrystals (CNCs) by conductometric titration are discussed. CNCs from sulfuric acid hydrolysis are electrostatically stabilized in aqueous suspension due to the introduction of charged sulfate ester groups onto the surface of the crystallites during reaction. The sulfur content thus largely reflects the surface charge of the crystals, and is crucial to the characterization and understanding of material properties. Conductometric titration is commonly used to quantify the sulfur content of CNCs, however, the exhaustive removal of free acid by dialysis and the necessity, type, quantity and duration of ion-exchange resin treatments are not always consistent. Here we explore the standard conditions of dialysis, ion-exchange, and the reproducibility of titration results. Extensive dialysis is found to be effective in the removal of free acid, but similar results are also achieved in shorter times and with less water using membrane ultrafiltration. It is also shown that the conditions of ion-exchange most commonly employed in the literature can lead to inaccurate sulfur contents. Finally, good agreement is obtained between the sulfur contents of different CNC batches prepared using the same hydrolysis conditions, and from titration and elemental analysis when thoroughly purified, well-dispersed samples, and appropriate resin conditions are used.     

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX₂). Use of a different halide on ZnX₂ dictates the selectivity, wherein the NaH‐ZnI₂ system delivers alcohols and NaH‐ZnCl₂ gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH₂)_∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H?Zn?Cl)₂ is the key species for the production of amines.     

An Efficient Preparation of 2,6-Di-t-Butyl-1,4-Benzoquinone

A convenient and high yielding preparation of 2,6-di-t-butyl-1,4-benzoquinone from the iron-catalyzed oxidation of 2,4,6-tri-t-butylphenol with t-butyl hydroperoxide (TBHP) under acidic conditions is reported.     

Microwave-assisted solid-phase synthesis of peptoids

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]     

Preparation and X-ray crystal structures of mixed ligand complexes containing the S3N ligand

Reaction of Hg(S₇N)₂ with cis- PtCl₂(PR₃)₂ (PR₃ = PPh₃, PPh₂Me, PPHMe₂, PEt₃) in the presence of Na[PF₆] gives [Pt(S₃N)(PR₃)₂][PF₆] in 32–46% yield. The complexes have been characterized by IR, NMR and microanalyses. The X-ray crystal structures of two examples (PR₃ = PPh₂Me and PEt₃) show that the S₃N⁻ ligand coordinates in a bidentate fashion via two sulphur atoms.