HSQC-ADEQUATE correlation: a new paradigm for establishing a molecular skeleton

Various experimental methods have been developed to unequivocally identify vicinal neighbor carbon atoms. Variants of the HMBC experiment intended for this purpose have included 2J3J-HMBC and H2BC. The 1,1-ADEQUATE experiment, in contrast, was developed to accomplish the same goal but relies on the (1) J(CC) coupling between a proton-carbon resonant pair and the adjacent neighbor carbon. Hence, 1,1-ADEQUATE can identify non-protonated adjacent neighbor carbons, whereas the 2J3J-HMBC and H2BC experiments require both neighbor carbons to be protonated to operate. Since 1,1-ADEQUATE data are normally interpreted with close reference to an HSQC spectrum of the molecule in question, we were interested in exploring the unsymmetrical indirect covariance processing of multiplicity-edited GHSQC and 1,1-ADEQUATE spectra to afford an HSQC-ADEQUATE correlation spectrum that facilitates the extraction of carbon-carbon connectivity information. The HSQC-ADEQUATE spectrum of strychnine is shown and the means by which the carbon skeleton can be conveniently traced is discussed.     

Benzenoid isomer enumeration and a new topological paradigm

Benzenoid isomer series possessing a constant number of isomers are reviewed. The benzenoid series having the same isomer number possess a one-to-one matching among their benzenoid membership in regard to molecular symmetry. These results are supplemented and clarified. For a given number of carbons, information regarding all the more stable benzenoids of potential interest to experimentalists is contained in these results.     

Ion mobility–mass spectrometry: a new paradigm for proteomics

Matrix-assisted laser desorption/ionization (MALDI) coupled with ion mobility–mass spectrometry (IM–MS) provides a rapid (μs–ms) means for the two-dimensional (2D) separation of complex biological samples (e.g., peptides, oligonucleotides, glycoconjugates, lipids, etc.), elucidation of solvent-free secondary structural elements (e.g., helices, β-hairpins, random coils, etc.), rapid identification of post-translational modifications (e.g., phosphorylation, glycosylation, etc.) or ligation of small molecules, and simultaneous and comprehensive sequencing information of biopolymers. In IM–MS, protein-identification information is complemented by structural characterization data, which is difficult to obtain using conventional proteomic techniques. New avenues for enhancing the figures of merit (e.g., sensitivity, limits of detection, dynamic range, and analyte selectivity) and optimizing IM–MS experimental parameters are described in the context of deriving new information at the forefront of proteomics research.     

Quantum mechanics: a new tool for engineering thermodynamics

Computational quantum mechanics is leading to new, theoretically based methods for the prediction of thermodynamic properties and phase behavior of interest to engineers. Three such methods we have been working on are reviewed here. In the most direct and computational intensive form, computational quantum mechanics is used to obtain information on the multidimensional potential energy surface between molecules, which is then used in computer simulation to predict thermodynamic properties and phase equilibria. At present, this method is limited to the study of small molecules due to the computational resources available. The second method is much less computationally intensive and provides a way to improve group-contribution methods by introducing corrections based on the charge and dipole moment of each functional group that is unique to the molecule in which it appears. The final method we consider is based on the polarizable continuum model, in which the free energy of transferring a molecule from an ideal gas to a liquid solution is computed, leading directly to values of activity coefficients and phase equilibrium calculations.     

Mechanism for the noncovalent chiral domino effect: new paradigm for the chiral role of the N-terminal segment in a 3(10)-helix

Recently, novel chiral interactions on 3(10)-helical peptides, of which the helicity is controlled by external chiral stimulus operating on the N-terminus, were proposed as a "noncovalent chiral domino effect (NCDE)" (Inai, Y.; et al. J. Am. Chem. Soc. 2000, 122, 11731. Inai, Y.; et al. J. Am. Chem. Soc. 2002, 124, 2466). The present study clarifies the mechanism for generating the NCDE. For this purpose, achiral nonapeptide (1), H-beta-Ala-(Delta(Z)Phe-Aib)(4)-OMe [Delta(Z)Phe = (Z)-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], was synthesized. Peptide 1 alone adopts a 3(10)-helical conformation in chloroform. On the basis of the induced CD signals of peptide 1 with chiral additives, chiral acid enabling the predominant formation of a one-handed helix was shown to need at least both carboxyl and urethane groups; that is, Boc-l-amino acid (Boc = tert-butoxycarbonyl) strongly induces a right-handed helix. NMR studies (NH resonance variations, low-temperature measurement, and NOESY) were performed for a CDCl(3) solution of peptide 1 and chiral additive, supporting the view that the N-terminal H-beta-Ala-Delta(Z)Phe-Aib, including the two free amide NH's, captures effectively a Boc-amino acid molecule through three-point interactions. The H-beta-Ala's amino group binds to the carboxyl group to form a salt bridge, while the Aib(3) NH is hydrogen-bonded to either oxygen of the carboxylate group. Subsequently, the free Delta(Z)Phe(2) NH forms a hydrogen bond to the urethane carbonyl oxygen. A semiempirical molecular orbital computation explicitly demonstrated that the dynamic looping complexation is energetically permitted and that the N-terminal segment of a right-handed 3(10)-helix binds more favorably to a Boc-l-amino acid than to the corresponding d-species. In conclusion, the N-terminal segment of a 3(10)-helix, ubiquitous in natural proteins and peptides, possesses the potency of chiral recognition in the backbone itself, furthermore enabling the conversion of the terminally acquired chiral sign and power into a dynamic control of the original helicity and helical stability.     

A new paradigm in N-heterocyclic carbenoid ligands

We report a new class of very readily prepared chiral N-heterocyclic carbenoid ligand that also contains two different types of chirality: an asymmetric centre and an atropoisomeric unit, but contained in two separate N-substituents, such that both can easily be varied. In addition to its simplicity and flexibility, this approach has potential advantages over systems containing only atropoisomeric units, because the inclusion of an additional fixed asymmetric centre means that the atropoisomers are diastereoisomers and therefore chemically distinct entities. Complexation to a metal centre increases the barrier to rotation in the atropoisomeric unit so that the two diastereoisomers may be separable by simple methods such as standard chromatography. In addition, a novel cis-substituted palladium complex has been characterised by X-ray crystallography.     

Sortase-mediated protein ligation: a new method for protein engineering

Sortase (SrtA), a transpeptidase from Staphylococcus aureus, catalyzes a cell-wall sorting reaction at an LPXTG motif by cleaving between threonine and glycine and subsequently joining the carboxyl group of threonine to an amino group of pentaglycine on the cell wall peptidoglycan. We have applied this transpeptidyl activity of sortase to in vitro protein ligation. We found that in the presence of sortase, protein/peptide with an LPXTG motif can be specifically ligated to an aminoglycine protein/peptide via an amide bond. Additionally, sortase can even conjugate substrates such as (d)-peptides, synthetic branched peptides, and aminoglycine-derivatized small molecules to the C terminus of a recombinant protein. The sortase-mediate protein ligation is robust, specific, and easy to perform, and can be widely applied to specific protein conjugation with polypeptides or molecules of unique biochemical and biophysical properties.     

Aqueous dispersion polymerization: a new paradigm for in situ block copolymer self-assembly in concentrated solution

Reversible addition-fragmentation chain transfer polymerization has been utilized to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macromolecular chain transfer agent based on poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has been elucidated for this aqueous dispersion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described in the literature, this strategy enables the facile, efficient, and reproducible preparation of diblock copolymer spheres, worms, or vesicles directly in concentrated aqueous solution. Chain extension of the highly hydrated zwitterionic PMPC block with HPMA in water at 70 °C produces a hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in situ self-assembly to form well-defined diblock copolymer spheres, worms, or vesicles. The final particle morphology obtained at full monomer conversion is dictated by (i) the target degree of polymerization of the PHPMA block and (ii) the total solids concentration at which the HPMA polymerization is conducted. Moreover, if the targeted diblock copolymer composition corresponds to vesicle phase space at full monomer conversion, the in situ particle morphology evolves from spheres to worms to vesicles during the in situ polymerization of HPMA. In the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the direct, reproducible, and highly efficient preparation of either block copolymer vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous solution.     

A new tool in peptide engineering: a photoswitchable stilbene-type beta-hairpin mimetic

Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogenous peptides with new physicochemical and pharmacological properties. The development, synthesis, photochemical investigation, and conformational analysis of a stilbene-type beta-hairpin mimetic capable of light-triggered conformational changes have been achieved. In addition to standard spectroscopic techniques (nuclear Overhauser effects, amide temperature coefficients, circular dichroism spectroscopy), the applicability of self-diffusion measurements (longitudinal eddy current delay pulsed-field gradient spin echo (LED-PGSE) NMR technique) in conformational studies of oligopeptides is demonstrated. The title compound shows photoisomerization of the stilbene chromophore, resulting in a change in solution conformation between an unfolded structure and a folded beta-hairpin.     

Zr(7)Sb(4): a new binary zirconium-rich antimonide

Zr(7)Sb(4) has been prepared by arc-melting of the elemental components and annealing at 1000-1150 degrees C. Its crystal structure was determined by X-ray diffraction (Pearson symbol mP44, monoclinic, space group P2(1)/c, Z = 4, a = 8.4905(6) A, b = 11.1557(8) A, c = 11.1217(8) A, beta = 111.443(2) degrees at 295 K). Zr(7)Sb(4) is isotypic to Hf(6)TiSb(4), a compound stabilized by differential fractional site occupancy. It is the first binary group-4 antimonide with this metal-to-antimony ratio, but it differs from the corresponding phosphides and arsenides M(7)Pn(4) (M = Ti, Zr, Hf; Pn = P, As), which adopt the Nb(7)P(4)-type structure. Zr(7)Sb(4) is built up from layers excised from the tetragonal W(5)Si(3)-type structure; these layers are displaced relative to each other to maximize interlayer Zr-Zr and Zr-Sb bonding, as confirmed by band structure calculations.     

Ligand-catalyzed asymmetric alkynylboration of enones: a new paradigm for asymmetric synthesis using organoboranes

Asymmetric conjugate alkynylation of enones may be effected using a B-1-alkynyldiisopropylboronate and catalytic amounts of binaphthol ligands. The high enantioselectivities observed are comparable to those obtained using stoichiometric amounts of binaphthol-modified boronate reagents, suggesting that this is a ligand-accelerated process. This is the first demonstration that catalytic amounts of chiral diols can be used with boronates to effect high levels of stereochemical control.     

Wrinkle engineering: a new approach to massive graphene nanoribbon arrays

Wrinkles are often formed on CVD-graphene in an uncontrollable way. By designing the surface morphology of growth substrate together with a suitable transfer technique, we are able to engineer the dimension, density, and orientation of wrinkles on transferred CVD-graphene. Such kind of wrinkle engineering is employed to fabricate highly aligned graphene nanoribbon (GNR) arrays by self-masked plasma-etching. Strictly consistent with the designed wrinkles, the density of GNR arrays varied from ～0.5 to 5 GNRs/μm, and over 88% GNRs are less than 10 nm in width. Electrical transport measurements of these GNR-based FETs exhibit an on/off ratio of ～30, suggesting an opened bandgap. Our wrinkle engineering approach allows very easily for a massive production of GNR arrays with bandgap-required widths, which opens a practical pathway for large-scale integrated graphene devices.     

Halogen bonding: a paradigm in supramolecular chemistry

The term halogen bonding describes the tendency of halogen atoms to interact with lone pair possessing atoms. The binding features and structural properties of halogen bonding are discussed and applied to drive the intermolecular self-assembly of hydrocarbons and perfluorocarbons in chemo-, site-, and enantioselective supramolecular synthesis. The halogen bonding is thus an effective and reliable tool in crystal engineering at the disposal of the supramolecular chemist.     

Regiochemical control of monolignol radical coupling: a new paradigm for lignin and lignan biosynthesis

BACKGROUND: Although the lignins and lignans, both monolignol-derived coupling products, account for nearly 30% of the organic carbon circulating in the biosphere, the biosynthetic mechanism of their formation has been poorly understood. The prevailing view has been that lignins and lignans are produced by random free-radical polymerization and coupling, respectively. This view is challenged, mechanistically, by the recent discovery of dirigent proteins that precisely determine both the regiochemical and stereoselective outcome of monolignol radical coupling. RESULTS: To understand further the regulation and control of monolignol coupling, leading to both lignan and lignin formation, we sought to clone the first genes encoding dirigent proteins from several species. The encoding genes, described here, have no sequence homology with any other protein of known function. When expressed in a heterologous system, the recombinant protein was able to confer strict regiochemical and stereochemical control on monolignol free-radical coupling. The expression in plants of dirigent proteins and proposed dirigent protein arrays in developing xylem and in other lignified tissues indicates roles for these proteins in both lignan formation and lignification. CONCLUSIONS: The first understanding of regiochemical and stereochemical control of monolignol coupling in lignan biosynthesis has been established via the participation of a new class of dirigent proteins. Immunological studies have also implicated the involvement of potential corresponding arrays of dirigent protein sites in controlling lignin biopolymer assembly.     

Reversing the discovery paradigm: a new approach to the combinatorial discovery of fluorescent chemosensors

We report here a new approach to the discovery of fluorescent chemosensors in which a new signaling mechanism allows a core fluorophore to be used in a combinatorial search for new binding events, thus reversing the reigning discovery paradigm.