N-Ethynylation of Anilides Decreases the Double-Bond Character of Amide Bond while Retaining trans-Conformation and Planarity

Activated amide bonds have been attracting intense attention; however, most of the studied moieties have twisted amide character. To add a new strategy to activate amide bonds while maintaining its planarity, we envisioned the introduction of an alkynyl group on the amide nitrogen to disrupt amide resonance by nN→C_sp conjugation. In this context, the conformations and properties of N-ethynyl-substituted aromatic amides were investigated by DFT calculations, crystallography, and NMR spectroscopic analysis. In contrast to the cis conformational preference of N-ethyl- and vinyl-substituted acetanilides, N-ethynyl-substituted acetanilide favors the trans conformation in the crystal and in solution. It also has a decreased double bond character of the C(O)−N bond, without twisting of the amide. N-Ethynyl-substituted acetanilides undergo selective C(O)−N bond or N−C(sp) bond cleavage reactions and have potential applications as activated amides for coupling reactions or easily cleavable tethers.     

Development of α‐Gal–Antibody Conjugates to Increase Immune Response by Recruiting Natural Antibodies

Cancer treatment with antibodies (Abs) is one of the most successful therapeutic strategies for obtaining high selectivity. In this study, α‐gal–Ab conjugates were developed that dramatically increased cellular cytotoxicity by recruiting natural Abs through the interaction between α‐gal and anti‐gal Abs. The potency of the α‐gal–Ab conjugates depended on the amount of α‐gal conjugated to the antibody: the larger the amount of α‐gal introduced, the higher the level of cytotoxicity observed. The conjugation of antibodies with an α‐gal dendrimer allowed the introduction of large amounts of α‐gal to the Ab, without loss of affinity for the target cell. The method described here will enable the re‐development of Abs to improve their potency.     

A photo‐degradable helix: Synthesis,structure, and photolysis of optically active poly[2,7‐bis(4‐t‐butylphenyl)‐9‐methylfluoren‐9‐yl acrylate]

2,7‐Bis(4‐t‐butylphenyl)‐9‐methylfluoren‐9‐yl acrylate ( BBPMFA ) was synthesized and polymerized using α,α′‐azobisisobutyronitrile or n‐Bu₃B‐air as a radical initiator and using the complex of 9‐fluorenyllithium with (S)‐(+)‐1‐(2‐pyrrolidinylmethyl)pyrrolidine as an optically active anionic initiator. Although the radical polymerization led to rather low‐molecular‐weight products at low yields, the anionic polymerization afforded polymers with higher molecular weights in higher yields. The poly( BBPMFA ) obtained by the anionic polymerization was slightly rich in isotacticity (meso diad 57%) and showed an intense circular dichroism (CD) spectrum and large dextrorotation. The intensity of the CD spectrum and magnitude of optical activity increased with an increase in M_n, suggesting that the polymer possesses a preferred‐handed helical conformation. The CD spectrum disappeared within 1 s on irradiation to the polymer in a CHCl₃ solution using a 500‐W Hg‐Xe lamp. This was ascribed to fast photolysis of the ester linkage leading to a loss of helical conformation of the entire chain. Photolysis products of poly( BBPMFA ) were poly(acrylic acid) and 2,7‐bis(4‐t‐butylphenyl)‐9‐methylenefluorene (2,7‐bis(4‐t‐butylphenyl)dibenzofulvene). The photolysis reaction seemed to proceed through the “unzipping” mechanism. The rate constant of photolysis of poly( BBPMFA ) under irradiation at monochromated 325 nm was around 0.01 s^?1 independent of molecular weight. Photolysis at 325 nm was approximately 2400 times faster than that for chemical ester solvolysis under a neutral condition in the dark. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Modified Protein-Water Interactions in CHARMM36m for Thermodynamics and Kinetics of Proteins in Dilute and Crowded Solutions

Proper balance between protein-protein and protein-water interactions is vital for atomistic molecular dynamics (MD) simulations of globular proteins as well as intrinsically disordered proteins (IDPs). The overestimation of protein-protein interactions tends to make IDPs more compact than those in experiments. Likewise, multiple proteins in crowded solutions are aggregated with each other too strongly. To optimize the balance, Lennard-Jones (LJ) interactions between protein and water are often increased about 10% (with a scaling parameter, λ = 1.1) from the existing force fields. Here, we explore the optimal scaling parameter of protein-water LJ interactions for CHARMM36m in conjunction with the modified TIP3P water model, by performing enhanced sampling MD simulations of several peptides in dilute solutions and conventional MD simulations of globular proteins in dilute and crowded solutions. In our simulations, 10% increase of protein-water LJ interaction for the CHARMM36m cannot maintain stability of a small helical peptide, (AAQAA)₃ in a dilute solution and only a small modification of protein-water LJ interaction up to the 3% increase (λ = 1.03) is allowed. The modified protein-water interactions are applicable to other peptides and globular proteins in dilute solutions without changing thermodynamic properties from the original CHARMM36m. However, it has a great impact on the diffusive properties of proteins in crowded solutions, avoiding the formation of too sticky protein-protein interactions.     

Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with β-cyclodextrin (HEPT7G/βCD; SunActive^® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/βCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet–visible absorption (UV–vis), ¹H- and ¹³C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC–MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job’s plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of β-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the β-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/βCD inclusion complex has both –2S and –2R stereoisomers of hesperetin-7-O-glucoside possibly in the –2S/–2R epimeric ratio of 1/1.43 (i.e., –2S: 41.1% and –2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in β-CD is complete inclusion, wherein both ends of HEPT7G are included in the β-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with β-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.     

Computational method for the retarded potential in the real‐time simulation of quantum electrodynamics

We discuss the method to compute the integrals, which appear in the retarded potential term for a real‐time simulation based on quantum electrodynamics. We show that the oscillatory integrals over the infinite interval involved in them can be efficiently performed by the method developed by Ooura and Mori based on the double exponential formula. © 2016 Wiley Periodicals, Inc.     

Controlled intramolecular electron transfers in cyanide-bridged molecular squares by chemical modifications and external stimuli

A series of cyanide bridged Fe-Co molecular squares, [Co(2)Fe(2)(CN)(6)(tp*)(2)(dtbbpy)(4)](PF(6))(2)·2MeOH (1), [Co(2)Fe(2)(CN)(6)(tp*)(2)(bpy)(4)](PF(6))(2)·2MeOH (2), and [Co(2)Fe(2)(CN)(6)(tp)(2)(dtbbpy)(4)](PF(6))(2)·4H(2)O (3) (tp = hydrotris(pyrazol-1-yl)borate, tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate, bpy =2,2'-bipyridine, dtbbpy =4,4'-di-tert-butyl-2,2'-bipyridine), were prepared by the reactions of [Fe(CN)(3)(L)](-) (L = tp or tp*) with Co(2+) and bidentate ligands (bpy or dtbbpy) in MeOH. In the molecular squares, Fe and Co ions are alternately bridged by cyanide ions, forming macrocyclic tetranuclear cores. Variable temperature X-ray structural analyses and magnetic susceptibility measurements confirmed that 1 exhibits two-step charge-transfer induced spin transitions (CTIST) centered at T(1/2) = 275 and 310 K in the solid state. The Fe and Co ions in 1 are the low-spin (LS) Fe(III) and high-spin (HS) Co(II) ions, described here in the high-temperature (HT) phase ([Fe(III)(LS2)Co(II)(HS2)]) at 330 K, while a low-temperature (LT) phase ([Fe(II)(LS2)Co(III)(LS2)]) with LS Fe(II) and Co(III) ions was dominant below 260 K. X-ray structural analysis revealed that in the intermediate (IM) phase at 298 K 1 exhibits positional ordering of [Fe(III)(LS2)Co(II)(HS2)] and [Fe(II)(LS2)Co(III)(LS2)] species with the 2:2 ratio. In photomagnetic experiments on 1, light-induced CTIST from the LT to the HT phase was observed by excitation of Fe(II) → Co(III) intervalence charge transfer (IVCT) band at 5 K and the trapped HT phase thermally relaxed to the LT phase in a two-step fashion. On the other hand, 2 and 3 are in the HT and LT phases, respectively, throughout the entire temperature range measured, and no CTIST was observed. UV-vis-NIR absorption spectral measurements and cyclic voltammetry in solution revealed that the different electronic states in 1-3 are ascribable to the destabilization of iron and cobalt ion d-orbitals by the introduction of methyl and tert-butyl groups to the ligands tp and bpy, respectively. Temperature dependence of UV-vis-NIR spectra confirmed that 1 exhibited a one-step CTIST in butyronitrile, of which T(1/2) varied from 227 to 280 K upon the addition of trifluoroacetic acid.     

Reactivity analysis of ammonium dinitramide binary mixtures based on ab initio calculations and thermal analysis

Ammonium dinitramide (ADN) is a promising high energy oxidizer for rocket propellants because it offers a good oxygen balance and has a significant energy content. As a result, ADN-based energetic ionic liquid propellants (EILPs) have been studied, based on ADN combined with urea and monomethyl ammonium nitrate (MMAN). The thermal decomposition of ADN in the condensed phase affects the combustion of both pure ADN and ADN-based EILPs; thus, it is important to understand the reactions of EILPs in the condensed phase. The present study assessed the reactivity of ADN mixtures in the condensed phase, focussing on hydrogen abstraction reactions with NO₂· formed from the thermal decomposition of ADN. The potential energy surfaces of these reactions were obtained using ab initio calculations. The effects of functional groups and of carbon chain length on hydrogen abstraction by NO₂· were examined. Mixtures of ADN with urea and acetamide (AA) as amide compounds, and with MMAN and monoethanol amine nitrate (MEAN) as nitrate salts, were examined. Thermal analysis was conducted to investigate the properties of these mixtures, using differential scanning calorimetry (DSC). The calculation results shows that AA and MEAN are more reactive with ADN than urea and MMAN, which is supported by the DSC data. Hydrogen abstraction by NO₂· is evidently an important condensed phase reaction in ADN mixtures, and substances having alkyl groups and longer carbon chains are more highly reactive.

     

Two-dimensional surface chirality control by solvent-induced helicity inversion of a helical polyacetylene on graphite

We report the direct evidence for the macromolecular helicity inversion of a helical poly(phenylacetylene) bearing l- or d-alanine pendants with a long alkyl chain in different solvents by atomic force microscopy observations of the diastereomeric helical structures. The diastereomeric helical poly(phenylacetylene)s induced in polar and nonpolar solvents self-assembled into ordered, two-dimensional helix bundles with controlled molecular packing, helical pitch, and handedness on graphite upon exposure of each solvent. The macromolecular helicity deposited on graphite from a polar solvent further inverted to the opposite handedness by exposure to a specific nonpolar solvent, and these changes in the surface chirality based on the inversion of helicity could be visualized by atomic force microscopy with molecular resolution, and the results were quantified by X-ray diffraction of the oriented liquid crystalline, diastereomeric helical polymer films.