Supramolecular Chirality: Vesicle-to-Chiral Helix Transition of the Micelles Consisting of a Sugar-Bearing Calix[4]arene Surfactant

Supramolecular self-assembly and the resulting chiral transfer from the molecular level to the nanoscale is a major topic in modern supramolecular chemistry. We synthesized a galactose-bearing calix[4]­arene surfactant (chiral) and mixed it with a primary amine-bearing analogue (achiral). The mixture showed strong induced circular dichroism (ICD) at an almost 3:2 molar ratio of the two surfactants, and exothermic heat was observed upon mixing. The magnitude of Δ<i>H</i> was comparable to that of van der Waals interactions. This phenomenon indicated that the ICD can be ascribed to the formation of a new supramolecular assembly in which the stoichiometric interaction between the two molecules leads to complexation and the resultant complex has chiral morphology. Transmission electron microscopy and small-angle X-ray scattering showed that the galactose-bearing surfactant forms vesicles, and the mixing induces a transition from the vesicles to threadlike cylinders with a diameter of ∼3.0 nm. We presume that these cylinder are twisted because of chiral transfer from the chiral galactose moiety and show ICD

Adjuvant Activity Enhanced by Cross-Linked CpG-Oligonucleotides in β‑Glucan Nanogel and Its Antitumor Effect

Cancer vaccine has the ability to directly eradicate tumor cells by creating and activating cytotoxic T lymphocytes (CTLs). To achieve efficient CTL activity and to induce Th1 responses, it is essential to administer an appropriate adjuvant as well as an antigen. CpG-ODN is known as a ligand of Toll-like receptor 9 (TLR9) and strongly induces Th1 responses. In our previous study, we developed a CpG-ODN delivery system by use of the formation of complexes between ODN and a β-glucan SPG, denoted as CpG/SPG, and demonstrated that CpG/SPG induces high Th1 responses. In this study, we created a nanogel made from CpG/SPG complexes through DNA–DNA hybridization (cross-linked (CL)-CpG). Immunization with CL-CpG induced much stronger antigen-specific Th1 responses in combination with the antigenic protein ovalbumin (OVA) than that with CpG/SPG. Mice preimmunized with CL-CpG and OVA exhibited a long delay in tumor growth and an improved survival rate after tumor inoculation. These immune inductions can be attributed to the improvement of cellular uptake by the combination of increased size and the cluster effect of the β-glucan recognition site in the nanogel structure. In other words, the particle nature of CL-CpG, instead of the semiflexible rod conformation of CpG/SPG, enhanced the efficacy of a cancer vaccine. The present results indicate that CL-CpG can be used as a potent vaccine adjuvant for the treatment of cancers and infectious diseases

Self-Assembly of Calix[4]arene-Based Amphiphiles Bearing Polyethylene Glycols: Another Example of “Platonic Micelles”

The aggregation number of classical micelles exhibits a certain distribution, which is a recognizable feature of conventional micelles. However, we recently identified perfectly monodisperse calix[4]­arene-based micelles whose aggregation numbers agree with the vertex numbers of regular polyhedra, that is, Platonic solids, and thus they are named “Platonic micelles”. Regarding our hypothesis of the formation mechanism of Platonic micelles, both repulsive interactions including steric hindrance and electrostatic repulsions among the headgroups are important for determining their aggregation number; however, neither of these is necessarily needed to consider. In this study, we employed polyethylene glycols (PEGs) as the nonionic headgroup of calix[4]­arene-based amphiphiles to study the effects of only repulsive interactions caused by steric hindrance on the formation of Platonic micelles. The amphiphiles containing relatively low-molecular-weight PEGs (550 or 1000 g mol^–1) form dodecamer or octamer micelles, respectively, with no variation in the aggregation number. However, relatively high-molecular-weight PEGs (2000 g mol^–1) produce polydispersed micelles with a range of aggregation number. PEG 2000 exhibits a greater affinity for water than PEG 550 and 1000, resulting in fewer hydrophobic interactions in micelle formation, as indicated by the drastic increase of the critical micelle concentration (CMC) value in the PEG 2000 system. The instability of the structure of PEG_2kCaL5 micelles might contribute to the higher mobility of PEG in the micellar shell, resulting in a non-Platonic aggregation number with polydispersity

On the Structural Origin of the Catalytic Properties of Inherently Strained Ultrasmall Decahedral Gold Nanoparticles

A new mechanism for reactivity of multiply twinned gold nanoparticles resulting from their inherently strained structure provides a further explanation of the surprising catalytic activity of small gold nanoparticles. Atomic defect structural studies of surface strains and quantitative analysis of atomic column displacements in the decahedral structure observed by aberration corrected transmission electron microscopy reveal an average expansion of surface nearest neighbor distances of 5.6%, with many strained by more than 10%. Density functional theory calculations of the resulting modified gold <i>d-</i>band states predict significantly enhanced activity for carbon monoxide oxidation. The new insights have important implications for the applications of nanoparticles in chemical process technology, including for heterogeneous catalysis

On the Structural Origin of the Catalytic Properties of Inherently Strained Ultrasmall Decahedral Gold Nanoparticles

A new mechanism for reactivity of multiply twinned gold nanoparticles resulting from their inherently strained structure provides a further explanation of the surprising catalytic activity of small gold nanoparticles. Atomic defect structural studies of surface strains and quantitative analysis of atomic column displacements in the decahedral structure observed by aberration corrected transmission electron microscopy reveal an average expansion of surface nearest neighbor distances of 5.6%, with many strained by more than 10%. Density functional theory calculations of the resulting modified gold <i>d-</i>band states predict significantly enhanced activity for carbon monoxide oxidation. The new insights have important implications for the applications of nanoparticles in chemical process technology, including for heterogeneous catalysis

Identification and Quantitative Assessment of Uremic Solutes as Inhibitors of Renal Organic Anion Transporters, OAT1 and OAT3

One of the characteristics of chronic kidney disease (CKD) is the accumulation of uremic solutes in the plasma. Less is known about the effects of uremic solutes on transporters that may play critical roles in pharmacokinetics. We evaluated the effect of 72 uremic solutes on organic anion transporter 1 and 3 (OAT1 and OAT3) using a fluorescent probe substrate, 6-carboxyfluorescein. A total of 12 and 13 solutes were identified as inhibitors of OAT1 and OAT3, respectively. Several of them inhibited OAT1 or OAT3 at clinically relevant concentrations and reduced the transport of other OAT1/3 substrates <i>in vitro.</i> Review of clinical studies showed that the active secretion of most drugs that are known substrates of OAT1/3 deteriorated faster than the renal filtration in CKD. Collectively, these data suggest that through inhibition of OAT1 and OAT3, uremic solutes contribute to the decline in renal drug clearance in patients with CKD

Strain Field in Ultrasmall Gold Nanoparticles Supported on Cerium-Based Mixed Oxides. Key Influence of the Support Redox State

Using a method that combines experimental and simulated Aberration-Corrected High Resolution Electron Microscopy images with digital image processing and structure modeling, strain distribution maps within gold nanoparticles relevant to real powder type catalysts, i.e., smaller than 3 nm, and supported on a ceria-based mixed oxide have been determined. The influence of the reduction state of the support and particle size has been examined. In this respect, it has been proven that reduction even at low temperatures induces a much larger compressive strain on the first {111} planes at the interface. This increase in compression fully explains, in accordance with previous DFT calculations, the loss of CO adsorption capacity of the interface area previously reported for Au supported on ceria-based oxides

Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo

Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-β and examined its synthesis. The 166 residue polypeptide chain of interferon-β was prepared by covalent condensation of two synthetic peptide segments and a glycosylated synthetic peptide bearing a complex-type glycan of biological origin. The peptides were covalently condensed by native chemical ligation. Selective desulfurization followed by deprotection of the two Cys­(Acm) residues gave the target full-length polypeptide chain of interferon-β bearing either a complex-type sialyl biantennary oligosaccharide or its asialo form. Subsequent folding with concomitant formation of the native disulfide bond afforded correctly folded homogeneous glycosyl-interferon-β. The chemically synthesized sialyl interferon-β exhibited potent antitumor activity in vivo

Imaging Nanostructural Modifications Induced by Electronic Metal−Support Interaction Effects at Au||Cerium-Based Oxide Nanointerfaces

A variety of advanced (scanning) transmission electron microscopy experiments, carried out in aberration-corrected equipment, provide direct evidence about subtle structural changes taking place at nanometer-sized Au||ceria oxide interfaces, which agrees with the occurrence of charge transfer effects between the reduced support and supported gold nanoparticles suggested by macroscopic techniques. Tighter binding of the gold nanoparticles onto the ceria oxide support when this is reduced is revealed by the structural analysis. This structural modification is accompanied by parallel deactivation of the CO chemisorption capacity of the gold nanoparticles, which is interpreted in exact quantitative terms as due to deactivation of the gold atoms at the perimeter of the Au||cerium oxide interface