Lithiated Polycalix[4]arenes for Efficient Adsorption of Iodine from Solution and Vapor Phases

Lithiated Polycalix[4]arenes for Efficient Adsorption of Iodine from Solution and Vapor Phase

Sequential Delivery of Doxorubicin and Zoledronic Acid to Breast Cancer Cells by CB[7]-Modified Iron Oxide Nanoparticles

Drug-loaded magnetic nanoparticles were synthesized and used for the sequential delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron oxide nanoparticles (IONPs) via phosphonate coordination to form <b>Z-NPs</b>. The unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to obtain <b>CZ-NPs</b>. Dox was complexed to the <b>CZ-NPs</b> to form the fully loaded particles (<b>DCZ-NPs</b>), which were stable in solution at 37 °C and physiological pH (7.4). Fluorescence spectroscopy established that Dox is released in solution from <b>DCZ-NPs</b> suddenly (i) when the particles are subjected to magnetically induced heating to 42 °C at low pH (5.0) and (ii) in the presence of glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in solution at low pH after Dox release. Magnetic measurements with a magnetic reader revealed that <b>DCZ-NPs</b> are internalized preferentially by MCF-7 cells versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when delivered by the particles. <b>DCZ-NPs</b> caused a decrease in the viability of MCF-7 cells that was greater than the net decrease caused when the drugs were added to the cells individually at concentrations equivalent to those delivered by the particles. MCF-7 cells were treated with <b>DCZ-NPs</b> and subjected to an alternating magnetic field (AMF) which, with the nanoparticles present, raised the temperature of the cells and triggered the intracellular release of Dox, as indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of the <b>DCZ-NPs</b> on MCF-7 cells were enhanced 10-fold by AMF-induced heating. <b>DCZ-NPs</b> were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro, indicating the potential of the particles to act as antimetastatic agents. Together these results demonstrate that <b>DCZ-NPs</b> warrant development as a system for combined chemo- and thermo-therapeutic treatment of cancer

Redox-Responsive Viologen-Mediated Self-Assembly of CB[7]-Modified Patchy Particles

Sulfonated surface patches of poly­(styrene)-based colloidal particles (CPs) were functionalized with cucurbit[7]­uril (CB[7]). The macrocycles served as recognition units for diphenyl viologen (DPV²⁺), a rigid bridging ligand. The addition of DPV²⁺ to aqueous suspensions of the particles triggered the self-assembly of short linear and branched chainlike structures. The self-assembly mechanism is based on hydrophobic/ion-charge interactions that are established between DPV²⁺ and surface-adsorbed CB[7]. DPV²⁺ guides the self-assembly of the CPs by forming a ternary DPV²⁺⊂(CB­[7])₂ complex in which the two CB[7] macrocycles are attached to two different particles. Viologen-driven particle assembly was found to be both directional and reversible. Whereas sodium chloride triggers irreversible particle disassembly, the one-electron reduction of DPV²⁺ with sodium dithionite causes disassembly that can be reversed via air oxidation. Thus, this bottom-up synthetic supramolecular approach allowed for the reversible formation and directional alignment of a 2D colloidal material

Solution-Phase Mechanistic Study and Solid-State Structure of a Tris(bipyridinium radical cation) Inclusion Complex

The ability of the diradical dicationic cyclobis­(paraquat-<i>p</i>-phenylene) (CBPQT^2(•+)) ring to form inclusion complexes with 1,1′-dialkyl-4,4′-bipyridinium radical cationic (BIPY^•+) guests has been investigated mechanistically and quantitatively. Two BIPY^•+ radical cations, methyl viologen (MV^•+) and a dibutynyl derivative (V^•+), were investigated as guests for the CBPQT^2(•+) ring. Both guests form trisradical complexes, namely, CBPQT^2(•+)⊂MV^•+ and CBPQT^2(•+)⊂V^•+, respectively. The structural details of the CBPQT^2(•+)⊂MV^•+ complex, which were ascertained by single-crystal X-ray crystallography, reveal that MV^•+ is located inside the cavity of the ring in a centrosymmetric fashion: the 1:1 complexes pack in continuous radical cation stacks. A similar solid-state packing was observed in the case of CBPQT^2(•+) by itself. Quantum mechanical calculations agree well with the superstructure revealed by X-ray crystallography for CBPQT^2(•+)⊂MV^•+ and further suggest an electronic asymmetry in the SOMO caused by radical-pairing interactions. The electronic asymmetry is maintained in solution. The thermodynamic stability of the CBPQT^2(•+)⊂MV^•+ complex was probed by both isothermal titration calorimetry (ITC) and UV/vis spectroscopy, leading to binding constants of (5.0 ± 0.6) × 10⁴ M^–1 and (7.9 ± 5.5) × 10⁴ M^–1, respectively. The kinetics of association and dissociation were determined by stopped-flow spectroscopy, yielding a <i>k</i>_f and <i>k</i>_b of (2.1 ± 0.3) × 10⁶ M^–1 s^–1 and 250 ± 50 s^–1, respectively. The electrochemical mechanistic details were studied by variable scan rate cyclic voltammetry (CV), and the experimental data were compared digitally with simulated data, modeled on the proposed mechanism using the thermodynamic and kinetic parameters obtained from ITC, UV/vis, and stopped-flow spectroscopy. In particular, the electrochemical mechanism of association/dissociation involves a bisradical tetracationic intermediate CBPQT^(2+)(•+)⊂V^•+ inclusion complex; in the case of the V^•+ guest, the rate of disassociation (<i>k</i>_b = 10 ± 2 s^–1) was slow enough that it could be detected and quantified by variable scan rate CV. All the experimental observations lead to the speculation that the CBPQT^(2+)(•+) ring of the bisradical tetracation complex might possess the unique property of being able to recognize both BIPY^•+ radical cation and π-electron-rich guests simultaneously. The findings reported herein lay the foundation for future studies where this radical–radical recognition motif is harnessed particularly in the context of mechanically interlocked molecules and increases our fundamental understanding of BIPY^•+ radical–radical interactions in solution as well as in the solid-state

Redox-Responsive Viologen-Mediated Self-Assembly of CB[7]-Modified Patchy Particles

Sulfonated surface patches of poly­(styrene)-based colloidal particles (CPs) were functionalized with cucurbit[7]­uril (CB[7]). The macrocycles served as recognition units for diphenyl viologen (DPV²⁺), a rigid bridging ligand. The addition of DPV²⁺ to aqueous suspensions of the particles triggered the self-assembly of short linear and branched chainlike structures. The self-assembly mechanism is based on hydrophobic/ion-charge interactions that are established between DPV²⁺ and surface-adsorbed CB[7]. DPV²⁺ guides the self-assembly of the CPs by forming a ternary DPV²⁺⊂(CB­[7])₂ complex in which the two CB[7] macrocycles are attached to two different particles. Viologen-driven particle assembly was found to be both directional and reversible. Whereas sodium chloride triggers irreversible particle disassembly, the one-electron reduction of DPV²⁺ with sodium dithionite causes disassembly that can be reversed via air oxidation. Thus, this bottom-up synthetic supramolecular approach allowed for the reversible formation and directional alignment of a 2D colloidal material

Radically Enhanced Molecular Switches

The mechanism governing the redox-stimulated switching behavior of a tristable [2]­rotaxane consisting of a cyclobis­(paraquat-<i>p</i>-phenylene) (CBPQT⁴⁺) ring encircling a dumbbell, containing tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) recognition units which are separated from each other along a polyether chain carrying 2,6-diisopropylphenyl stoppers by a 4,4′-bipyridinium (BIPY²⁺) unit, is described. The BIPY²⁺ unit acts to increase the lifetime of the metastable state coconformation (MSCC) significantly by restricting the shuttling motion of the CBPQT⁴⁺ ring to such an extent that the MSCC can be isolated in the solid state and is stable for weeks on end. As controls, the redox-induced mechanism of switching of two bistable [2]­rotaxanes and one bistable [2]­catenane composed of CBPQT⁴⁺ rings encircling dumbbells or macrocyclic polyethers, respectively, that contain a BIPY²⁺ unit with either a TTF or DNP unit, is investigated. Variable scan-rate cyclic voltammetry and digital simulations of the tristable and bistable [2]­rotaxanes and [2]­catenane reveal a mechanism which involves a bisradical state coconformation (BRCC) in which only one of the BIPY^•+ units in the CBPQT^2(•+) ring is oxidized to the BIPY²⁺ dication. This observation of the BRCC was further confirmed by theoretical calculations as well as by X-ray crystallography of the [2]­catenane in its bisradical tetracationic redox state. It is evident that the incorporation of a kinetic barrier between the donor recognition units in the tristable [2]­rotaxane can prolong the lifetime and stability of the MSCC, an observation which augurs well for the development of nonvolatile molecular flash memory devices

Viologen-Based Conjugated Covalent Organic Networks via Zincke Reaction

Morphology influences the functionality of covalent organic networks and determines potential applications. Here, we report for the first time the use of Zincke reaction to fabricate, under either solvothermal or microwave conditions, a viologen-linked covalent organic network in the form of hollow particles or nanosheets. The synthesized materials are stable in acidic, neutral, and basic aqueous solutions. Under basic conditions, the neutral network assumes radical cationic character without decomposing or changing structure. Solvent polarity and heating method determine product morphology. Depending upon solvent polarity, the resulting polymeric network forms either uniform self-templated hollow spheres (<b>HS</b>) or hollow tubes (<b>HT</b>). The spheres develop via an inside-out Ostwald ripening mechanism. Interestingly, microwave conditions and certain solvent polarities result in the formation of a robust covalent organic gel framework (<b>COGF</b>) that is organized in nanosheets stacked several layers thick. In the gel phase, the nanosheets are crystalline and form honeycomb lattices. The use of the Zincke reaction has previously been limited to the synthesis of small viologen molecules and conjugated viologen oligomers. Its application here expands the repertoire of tools for the fabrication of covalent organic networks (which are usually prepared by dynamic covalent chemistry) and for the synthesis of viologen-based materials. All three materials<b>HT</b>, <b>HS</b>, and <b>COGF</b>serve as efficient adsorbents of iodine due to the presence of the cationic viologen linker and, in the cases of <b>HT</b> and <b>HS</b>, permanent porosity