Regioselective Bromination of a Thymine–Acridine Conjugate by N-Bromosuccinimide

A thymine and acridine conjugate (1), containing a benzylic carbon of thymine and an electron-rich aromatic ring (acridine) within the same molecule, was synthesized. Treatment of 1 with N-bromosuccinimide (NBS) in anhydrous chloroform in the presence of azobisisobutylnitrile produced a dibromo-substituted thymine–acridine conjugate (7) as a major product, in which the bromination was only observed on the acridine ring. Nuclear Overhauser effect (NOE) difference spectroscopy revealed that the actual bromination substitution was on C-2 and C-7 of acridine. Our results suggest that electrophilic aromatic substitution, not the expected benzylic radical reaction, takes place predominantly even when 1 is subjected to the NBS reaction condition, which favors radical processes. In addition, such selectivity is clearly solvent dependent.     

Peptide Chirality Sensing by a Cyclodextrin–Polythiophene Conjugate

A new cyclodextrin–polythiophene conjugate ( CDPT ) has been prepared by attaching permethyl-α-cyclodextrins to polythiophene (PT) through a hexamethylene tether. Circular dichroism spectral examination of CDPT revealed that only a weak positive Cotton effect (Δε=0.1 M ⁻¹ cm⁻¹) was induced at the main band of the PT in dimethyl sulfoxide and similarly weak bisignate signals in pure and aqueous methanol solutions, which indicates that the α-cyclodextrins appended to PT with a long tether are ineffective in inducing a homochiral structure in the PT backbone. Nevertheless, enantiomeric amino acids and dipeptides added to an aqueous methanolic solution of CDPT caused chirality-dependent hypochromic changes in the UV/Vis spectra, which enabled us to sense these species and quantitatively determine the enantioselectivity by observing the difference in absorbance upon interaction with pairs of enantiomers. Enantiomeric d,d /l,l -dipeptide pairs rather than D /L -amino acid pairs were better differentiated in general, the highest dd /ll selectivity of 13.7 being observed for Phe-Phe.     

Chemistry of Anthracene–Acetylene Oligomers XX: Synthesis,Structures, and Self-Association of Anthracene–Anthraquinone Cyclic Compounds with Ethynylene Linkers

We have synthesized anthracene–acetylene oligomers, which contained one 10-substituted anthracene unit and one anthraquinone unit, by cyclization with Sonogashira coupling. X-ray analysis revealed an almost-planar framework and significant out-of-plane deformation around the inner carbonyl moiety because of steric hindrance. These compounds underwent self-association in solution and their association constants for monomer–dimer exchange were determined by variable-concentration ¹H NMR measurements in CDCl₃: 8 mol⁻¹ L (10-substituent: isopropyl), <5 mol⁻¹ L (methoxy), and 19 mol⁻¹ L (octyloxy). These results were discussed on the basis of spectroscopic and molecular-orbital analysis. A linear molecular assembly of the octyloxy compound at a liquid/graphite interface was observed by STM measurements.     

Structure-Guided Design of a Group B Streptococcus Type III Synthetic Glycan–Conjugate Vaccine

Identification of glycan functional epitopes is of paramount importance for rational design of glycoconjugate vaccines. We recently mapped the structural epitope of the capsular polysaccharide from type III Group B Streptococcus (GBSIII), a major cause of invasive disease in newborns, by using a dimer fragment (composed of two pentasaccharide repeating units) obtained by depolymerization complexed with a protective mAb. Although reported data had suggested a highly complex epitope contained in a helical structure composed of more than four repeating units, we showed that such dimer conjugated to a carrier protein with a proper glycosylation degree elicited functional antibodies comparably to the full-length conjugated polysaccharide. Here, starting from the X-ray crystallographic structure of the polysaccharide fragment–mAb complex, we synthesized a hexasaccharide comprising exclusively the relevant positions involved in binding. Combining competitive surface plasmon resonance and saturation transfer difference NMR spectroscopy as well as in-silico modeling, we demonstrated that this synthetic glycan was recognized by the mAb similarly to the dimer. The hexasaccharide conjugated to CRM₁₉₇, a mutant of diphtheria toxin, elicited a robust functional immune response that was not inferior to the polysaccharide conjugate, indicating that it may suffice as a vaccine antigen. This is the first evidence of an X-ray crystallography-guided design of a synthetic carbohydrate-based conjugate vaccine.     

Synthesis of a Novel Conjugate of Bromoarene and Polyamide Containing N-Methylimidazoles

DNA-photocleavage agents have generated considerable attention in chemistry,biology and medicine1,2,because their DNA-cleavage activities can be easily controlled by photoirradiation.In the past decade,several DNA-cleavage agents have been successfully attached to polyamide3,4,to obtain new conjugates with higher and specific DNA-cleavage activities.Most of them contain only one photocleavage group to induce single-strand breaks,and the conjugates inducing double-strand breaks have been ra…     

Synthesis of a Novel Conjugate of Dibenzoyldiazomethane and Polyamide Containing N-Methylimidazoles

A novel conjugate of dibenzoyldiazomethane and polyamide containing N-methylimidazoles was synthesized by a chloroform reaction and a DCC/HOBT coupling reaction.     

Synthesis of CMC-Multipeptide Conjugate

AlthoughbioactivePeptidesplayessentialpl~nacologicalroles,manyofUlemarelimitedintheiruseastrigsduetotheirrapidclearancefromtilebodyandlowstabilitytoprotCase.Besidesthemodificationoftilepeptidebackbone,suchaspseudopeptides,Peptides,andPeptide-nucleicacidetNA),covalentbondingpeptidewigalsomemolecules,suchasbranched-chainPOlrpeptidepeCP)andpolyethyleneglycol(PEG)',isanotheraPProachtoelthancePephdebioavailability.ThemeritofaPephde-POlymerconjugateiswithoutmutationinPeptidebackbonewhilegain…     

Analysis of Lanthanide π Complexes in Terms of Voronoi–Dirichlet Polyhedra

The structures of 112 rare-earth complexes were studied using Voronoi–Dirichlet polyhedra. A new method for identification of chemical bonding between atoms in organometallic compounds was proposed. The dependence of the area of action of a lanthanide atom (Ln) on its nature, coordination number, and oxidation number was investigated. The reasons for the formation of Ln···H aghostic contacts were considered within the framework of the geometric topological method of crystal-chemical analysis employed.     

Facile Regioselective Synthesis of a Novel Chitosan–Pexiganan Conjugate with Potential Interest for the Treatment of Infected Skin Lesions

A pexiganan–chitosan conjugate was designed to combine the exceptional bioadhesion and tissue-regenerating abilities of chitosan with the excellent antibiotic properties of pexiganan. We herein report our first results on the successful synthesis, including Fourier transform infrared (FT-IR) and amino acid analysis of such conjugate, which was prepared by regioselective covalent attachment of a Cys-containing pexiganan analog to the chitosan's amino groups. Further results from ongoing research will be reported.     

Synthesis and in Vitro Cytotoxicity of a Novel Conjugate of Polyamide and Phospholipid

Small molecules with the ability to target predetermined sequences of DNA would be valuable tools in molecular biology and potentially in human medicine1-3. Synthetic polyamides consisting of N-methylpyrrole (Py), N-methylimidazole (Im) have received spec…     

Intersystem Crossing in Naphthalenediimide–Oxoverdazyl Dyads: Synthesis and Study of the Photophysical Properties

Oxoverdazyl (Vz) radical units were covalently linked to the naphthalenediimide (NDI) chromophore to study the effect of the radical on the photophysical properties, especially the radical enhanced intersystem crossing (REISC), which is a promising approach to develop heavy-atom-free triplet photosensitizers. Rigid phenyl or ethynylphenyl linkers between the two moieties were used, thus REISC and formation of doublet (D₁, total spin quantum number S=1/2) and quartet states (Q₁, S=3/2) are anticipated. The photophysical properties of the dyads were studied with steady-state and femtosecond/nanosecond transient absorption (TA) spectroscopies and DFT computations. Femtosecond transient absorption spectra show a fast electron transfer (<150 fs), and ISC (ca. 1.4–1.85 ps) is induced by charge recombination (CR, in toluene). Nanosecond transient absorption spectra demonstrated a biexponential decay of the triplet state of the NDI moiety. The fast component (lifetime: 50 ns; population ratio: 80 %) is assigned to the D₁→D₀ decay, and the slow decay component (2.0 μs; 20 %) to the Q₁→D₀ ISC. DFT computations indicated ferromagnetic interactions between the radical and chromophore (J=0.07–0.13 eV). Reversible formation of the radical anion of the NDI moiety by photoreduction of the radical-NDI dyads in the presence of sacrificial electron donor triethanolamine (TEOA) is achieved. This work is useful for design of new triplet photosensitizers based on the REISC effect.     

Recognition of aromatic compounds by π pocket within a cage-shaped borate catalyst

Taking shape: the ability of a Lewis acid catalyst to distinguish between aromatic and aliphatic hydrocarbon moieties was accomplished by using cage-shaped borate catalysts B(OC(6)H(3)Aryl)(3)CH having a π pocket derived from aryl substituents surrounding the boron center. The catalyst predominantly activated aromatic aldehydes over aliphatic ones for reaction.     

Noncovalent Immobilization of Molecular Electrocatalysts for Chemical Synthesis: Efficient Electrochemical Alcohol Oxidation with a Pyrene–TEMPO Conjugate

Electrocatalytic methods for organic synthesis could offer sustainable alternatives to traditional redox reactions, but strategies are needed to enhance the performance of molecular catalysts designed for this purpose. The synthesis of a pyrene-tethered TEMPO derivative (TEMPO=2,2,6,6-tetramethylpiperidinyl-N-oxyl) is described, which undergoes facile in situ noncovalent immobilization onto a carbon cloth electrode. Cyclic voltammetry and controlled potential electrolysis studies demonstrate that the immobilized catalyst exhibits much higher activity relative to 4-acetamido–TEMPO, an electronically similar homogeneous catalyst. In preparative electrolysis experiments with a series of alcohol substrates and the immobilized catalyst, turnover numbers and frequencies approach 2 000 and 4 000 h⁻¹, respectively. The synthetic utility of the method is further demonstrated in the oxidation of a sterically hindered hydroxymethylpyrimidine precursor to the blockbuster drug, rosuvastatin.     

Spatiotemporally Coupled Photoactivity of Phthalocyanine–Peptide Conjugate Self-Assemblies for Adaptive Tumor Theranostics

Spatiotemporally coupled tumor phototheranostic platforms offer a flexible and precise system that takes the biological interaction between tumors and photoactive agents into consideration for optimizing treatment, which is highly consistent with precision medicine. However, the fabrication of monocomponent-based photoactive agents applicable to multifold imaging techniques and multiple therapies in a facile way remains challenging. In this study, we developed simple phthalocyanine–peptide (PF) conjugate-based monocomponent nanoparticles with spatiotemporally coupled photoactivity for adaptive tumor theranostics. The self-assembled PF nanoparticles possess well-defined spherical nanostructures and excellent colloidal stability along with supramolecular photothermal effects. Importantly, the PF nanoparticles showed switchable photoactivity triggered by their interactions with the cell membrane, which enables an adaptive transformation from photothermal therapy (PTT) and photoacoustic imaging (PAI) to photodynamic therapy (PDT) and corresponding fluorescence imaging (FI). Theranostic modalities are integrated in a spatiotemporally coupled manner, providing a facile, biocompatible and effective route for localized tumor phototherapy. This study offers a flexible and versatile strategy to integrate multiple theranostic modalities into a single component so that it can realize its full potential and thereby amplify its therapeutic efficacy, creating promising opportunities for the design of theranostics and further highlighting their clinical prospects to the diagnosis and treatment of cancers.     

Conjugate Addition of a Silyl Ketene Acetal to α,β‐Unsaturated Lactones

Abstract

Conjugate addition of a silyl ketene acetal [Me₂C?C (OMe)OSiMe₃] to α,β‐unsaturated lactones (namely, 5,6‐dihydro‐2H‐pyran‐2‐one, 2(5H)‐furanone as Michael acceptor) occurs efficiently at room temperature in the presence of a nucleophilic catalyst, tetra‐n‐butyl ammonium bibenzoate (TBABB), in THF as well as Lewis acid catalysts such as Yb(OTf)₃ and I₂ in CH₂Cl₂, giving the corresponding 1,4‐adducts in excellent yields.     

Lateral extension of π conjugation along the bay regions of bisanthene through a Diels-Alder cycloaddition reaction

Diels-Alder cycloaddition reactions at the bay regions of bisanthene (1) with dienophiles such as 1,4-naphthoquinone have been investigated. The products were submitted to nucleophilic addition followed by reductive aromatization reactions to afford the laterally extended bisanthene derivatives 2 and 3. Attempted synthesis of a larger expanded bisanthene 4 revealed an unexpected hydrogenation reaction at the last reductive aromatization step. Unusual Michael addition was observed on quinone 14, which was obtained by Diels-Alder reaction between 1 and 1,4-anthraquinone. Compounds 1-3 exhibited near-infrared (NIR) absorption and emission with high-to-moderate fluorescent quantum yields. Their structures and absorption spectra were studied by density function theory and non-planar twisted structures were calculated for 2 and 3. All compounds showed amphoteric redox behavior with multiple oxidation/reduction waves. Oxidative titration with SbCl(5) gave stable radical cations, and the process was followed by UV/Vis/NIR spectroscopic measurements. Their photostability was measured and correlated to their different geometries and electronic structures.     

Ochratoxin A in Some French Wines: Application of a Direct Competitive ELISA Based on an OTA–HRP Conjugate

Abstract

In the direct-competitive enzyme-linked immunosorbent assay (dc-ELISA) approach, an ochratoxin A–horseradish peroxidase (OTA–HRP) synthesized conjugate was utilized. Fluorescence studies revealed that when excited at 333 nm, the OTA–HRP conjugate shifted in fluorescence from 438 nm to 444 nm. At the 295-nm excitation wavelength, the tryptophan emission peak blue-shifted from 326 nm to 318 nm. Western blot analysis revealed that anti-OTA antibodies specifically binds and recognize the OTA–HRP conjugate. The dc-ELISA showed an IC₅₀ value of 400 ng/L and a linear working range (LWR) value between 100 and 1500 ng/L. The ELISA results were confirmed with high-performance liquid-chromatography (HPLC) analysis to assess the potential of the OTA–HRP conjugate.     

Ring opening metathesis polymerization of an η4-benzene complex: a direct synthesis of a polyacetylene with a regular pattern of π bound metal fragments

The complex (η(5)-C(5)H(5))Ir(η(4)-C(6)H(6)) reacts with Grubbs' catalyst to give a novel polyacetylene consisting of cyclopentadienyliridium bound s-cis butadiene moieties separated by C=C linkages. A crystal structure of the pentamethylcyclopentadienyl analog establishes a strong structural analogy with norbornadiene, a classical ROMP monomer.     

Stabilization of a π double bond between two boron atoms: A theoretical approach

The low-lying states of HBBH, HBBNH₂ and H₂NBBNH₂ are investigated by means of ab initio CI calculations using a double-zeta + polarization basis set. Diborene is found to have a ³∑_g⁻ ground state. Replacement of hydrogen by amino groups on each side of the BB bond leads to an ethylene-like bond which corresponds to a ¹A_g state of D_2h symmetry. π back-donation by the amino lone pairs is responsible for the stabilization of this state.