Ex^2Box: Interdependent Modes of Binding in a Two-Nanometer-Long Synthetic Receptor

Incorporation of two biphenylene-bridged 4,4′-bipyridinium extended viologen units into a para-phenylene-based cyclophane results in a synthetic receptor that is 2 nm long and adopts a box-like geometry. This cyclophane, Ex^2Box^4+, possesses the ability to form binary and ternary complexes with a myriad of guest molecules ranging from long π-electron-rich polycyclic aromatic hydrocarbons, such as tetracene, tetraphene, and chrysene, to π-electron-poor 2,6-dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-anthraquinone molecules. Moreover, Ex^2Box^4+ is capable of forming one-to-one complexes with polyether macrocycles that consist of two π-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex^2Box^4+ is such that the pyridinium rings located at the “ends” of the cyclophane are electron-poor and prefer to enter into donor–acceptor interactions with π-electron-rich guests, while the “middle” of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and can interact with π-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-one complexes which possess high stability constants in organic media. The binding affinity of Ex^2Box^4+ was investigated in the solid state by way of single-crystal X-ray diffraction and in solution by using UV–vis and NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the different modes of binding of Ex^2Box^4+ with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order to understand the degree with which each mode of binding contributes to the overall encapsulation of each guest

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Activation-Enabled Syntheses of Functionalized Pillar[5]arene Derivatives

A series of regioselective di- and trifunctionalized pillar[5]­arene derivatives have been synthesized by a deprotection-followed-by-activation strategy, and their constitutions have been established as a result of having access to their solid-state structures. De-<i>O</i>-methylation occurs in a stepwise manner at lower temperatures under kinetic control, affording the desired oligo-substituted pillar[5]­arene derivatives. In addition, the regioisomers of these derivatives can be isolated by installing triflate groups on the free hydroxyl groups

Activation-Enabled Syntheses of Functionalized Pillar[5]arene Derivatives

A series of regioselective di- and trifunctionalized pillar[5]­arene derivatives have been synthesized by a deprotection-followed-by-activation strategy, and their constitutions have been established as a result of having access to their solid-state structures. De-<i>O</i>-methylation occurs in a stepwise manner at lower temperatures under kinetic control, affording the desired oligo-substituted pillar[5]­arene derivatives. In addition, the regioisomers of these derivatives can be isolated by installing triflate groups on the free hydroxyl groups

ExBox: a polycyclic aromatic hydrocarbon scavenger

A template-directed protocol, which capitalizes on donor acceptor interactions, is employed to synthesize a semi-rigid cyclophane (ExBox(4+)) that adopts a box-like geometry and is comprised of pi-electron-poor 1,4-phenylene-bridged ("extended") bipyridinium units (ExBIPY(2+)). ExBox(4+) functions as a high-affinity scavenger of an array of different polycyclic aromatic hydrocarbons (PAHs), ranging from two to seven fused rings, as a result of its large, accommodating cavity (approximately 3.5 angstrom in width and 11.2 angstrom in length when considering the van der Waals radii) and its ability to form strong non-covalent bonding interactions with pi-electron-rich PAHs in either organic or aqueous media. In all, 11 PAH guests were observed to form inclusion complexes with ExBox(4+), with coronene being the largest included guest. Single-crystal X-ray diffraction data for the 11 inclusion complexes EaBox(4+)subset of PAH as well as UV/vis spectroscopic data for 10 of the complexes provide evidence of the promiscuity of ExBox(4+) for the various PAHs. Nuclear magnetic resonance spectroscopy and isothermal titration calorimetric analyses of 10 of the inclusion complexes are employed to further characterize the host guest interactions in solution and determine the degree with which ExBox(4+) binds each PAR compound. As a proof-of-concept, a batch of crude oil from Saudi Arabia was subjected to extraction with the water-soluble form of the PAH receptor, ExBox center dot 4Cl, resulting in the isolation of different aromatic compounds after ExBox center dot 4Cl was regenerated.A template-directed protocol, which capitalizes on donor− acceptor interactions, is employed to synthesize a semi-rigid cyclophane (ExBox4+) that adopts a box-like geometry and is comprised of π-electronpoor 1,4-phenylene-bridged (“extended”) bipyridinium units (ExBIPY2+). ExBox4+ functions as a high-affinity scavenger of an array of different polycyclic aromatic hydrocarbons (PAHs), ranging from two to seven fused rings, as a result of its large, accommodating cavity (approximately 3.5 Å in width and 11.2 Å in length when considering the van der Waals radii) and its ability to form strong non-covalent bonding interactions with π-electron-rich PAHs in either organic or aqueous media. In all, 11 PAH guests were observed to form inclusion complexes with ExBox4+, with coronene being the largest included guest. Single-crystal X-ray diffraction data for the 11 inclusion complexes ExBox4+⊂PAH as well as UV/vis spectroscopic data for 10 of the complexes provide evidence of the promiscuity of ExBox4+ for the various PAHs. Nuclear magnetic resonance spectroscopy and isothermal titration calorimetric analyses of 10 of the inclusion complexes are employed to further characterize the host−guest interactions in solution and determine the degree with which ExBox4+ binds each PAH compound. As a proof of-concept, a batch of crude oil from Saudi Arabia was subjected to extraction with the water-soluble form of the PAH receptor, ExBox·4Cl, resulting in the isolation of different aromatic compounds after ExBox·4Cl was regenerated

π-Dimerization of viologen subunits around the core of C60 from twelve to six directions

none11siMolecular reorganization around the core of C-60 has been achieved by electron transfer centered on pi-dimerizable viologen subunits located in a restricted region of space. Fullerene C-60 hexaadducts, featuring 12 viologen subunits, have been prepared by using copper-mediated Huisgen 1,3-dipolar cycloaddition of azides with alkynes. Detailed electrochemical studies, supported by UV-Vis and EPR spectroscopic analyses, demonstrate that the linkers bearing the viologen subunits attached to specific positions around the all-carbon sphere, allow the formation of six intramolecular pi-dimers. Theoretical calculations reveal that the close proximity of the orbitals of the viologen subunits attached to the C-60 facilitate the pi-dimerization of the bis-radical species. These investigations support the fact that the motion of discrete peripheral groups oriented around the all-carbon sphere of C-60 can be controlled electrochemically using noncovalent reversible interactions.mixedIehl, Julien; Frasconi, Marco; Jacquot De Rouville, Henri-Pierre; Renaud, Nicolas; Dyar, Scott M.; Strutt, Nathan L.; Carmieli, Ranaan; Wasielewski, Michael R.; Ratner, Mark A.; Nierengarten, Jean-François; Stoddart, J. FraserIehl, Julien; Frasconi, Marco; Jacquot De Rouville, Henri Pierre; Renaud, Nicolas; Dyar, Scott M.; Strutt, Nathan L.; Carmieli, Ranaan; Wasielewski, Michael R.; Ratner, Mark A.; Nierengarten, Jean François; Stoddart, J. Frase