Enhancing drug delivery with supramolecular amphiphilic macrocycle nanoparticles: selective targeting of CDK4/6 inhibitor palbociclib to melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surfaces by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

Enhancing Drug Delivery with Supramolecular Amphiphilic Macrocycle Nanoparticles: Selective Targeting of CDK4/6 Inhibitor Palbociclib to Melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn , and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

Electrochemical Performance of Polymer-Derived Silicon-Oxycarbide/Graphene Nanoplatelet Composites for High-Performance Li-Ion Batteries.

Amorphous polymer-derived silicon-oxycarbide (SiOC) ceramics have a high theoretical capacity and good structural stability, making them suitable anode materials for lithium-ion batteries. However, SiOC has low electronic conductivity, poor transport properties, low initial Couloumbic efficiency, and limited rate capability. Therefore, there is an urgent need to explore an efficient SiOC-based anode material that could mitigate the abovementioned limitations. In this study, we synthesized carbon-rich SiOC (SiOC-I) and silicon-rich SiOC (SiOC-II) and evaluated their elemental and structural characteristics using a broad spectrum of characterization techniques. Li-ion cells were fabricated for the first time by pairing a buckypaper composed of carbon nanotubes with SiOC-I or SiOC-II as the anode. When mixed with graphene nanoplatelets, the SiOC-II/GNP composites exhibited improved electrochemical performance. High specific capacity (average specific capacity of 744 mAh/g at a 0.1C rate) was achieved with the composite anode (25 wt % SiOC-II and 75% GNP), which was much better than that of monolithic SiOC-I, SiOC-II, or GNPs. This composite also exhibited excellent cycling stability, achieving 344 mAh/g after 260 cycles at a 0.5C rate and high reversibility. The enhanced electrochemical performance is attributed to better electronic conductivity, lower charge-transfer resistance, and short ion diffusion length. Due to their superior electrochemical performance, SiOC/GNP composites with CNT buckypaper as a current collector can be considered a promising anode material for LiBs.

Square-Facet Nanobar MOF-Derived Co3O4@Co/N-doped CNT Core-Shell-based Nanocomposites as Cathode Materials for High-Performance Supercapacitor Studies.

The binary as well as ternary nanocomposites of the square-facet nanobar Co-MOF-derived Co3O4@Co/N-CNTs (N-CNTs: nitrogen-doped carbon nanotubes) with Ag NPs and rGO have been synthesized via an easy wet chemical route, and their supercapacitor behavior was then studied. At a controlled pH of the precursor solution, square-facet nanobars of Co-MOF were first synthesized by the solvothermal method and then pyrolyzed under a controlled nitrogen atmosphere to get a core-shell system of Co3O4@Co/N-CNTs. In the second step, different compositions of Co3O4@Co/N-CNT core-shell structures were formed by an ex-situ method with Ag NPs and rGO moieties. Among several bare, binary, and ternary compositions tested in 6 M aqueous KOH electrolyte, a ternary nanocomposite having a 7.0:1.5:1.5 stoichiometric ratio of Co3O4@Co/N-CNT, Ag NPs, and rGO, respectively, reported the highest specific capacitance (3393.8 F g-1 at 5 mV s-1). The optimized nanocomposite showed the energy density, power density, and Coulombic efficiency of 74.1 W h.kg-1, 443.7 W.kg-1, and 101.3%, respectively, with excellent electrochemical stability. After testing an asymmetrical supercapacitor with a Co3O4@Co/N-CNT/Ag NPs/rGO/nickel foam cathode and an activated carbon/nickel foam anode, it showed 4.9 W h.kg-1 of energy density and 5000.0 W.kg-1 of power density.

Effects of intervalence charge transfer interaction between π-stacked mixed valent tetrathiafulvalene ligands on the electrical conductivity of 3D metal-organic frameworks.

Achieving a molecular-level understanding of how the structures and compositions of metal-organic frameworks (MOFs) influence their charge carrier concentration and charge transport mechanism-the two key parameters of electrical conductivity-is essential for the successful development of electrically conducting MOFs, which have recently emerged as one of the most coveted functional materials due to their diverse potential applications in advanced electronics and energy technologies. Herein, we have constructed four new alkali metal (Na, K, Rb, and Cs) frameworks based on an electron-rich tetrathiafulvalene tetracarboxylate (TTFTC) ligand, which formed continuous π-stacks, albeit with different π-π-stacking and S⋯S distances (d π-π and d S⋯S). These MOFs also contained different amounts of aerobically oxidized TTFTC˙+ radical cations that were quantified by electron spin resonance (ESR) spectroscopy. Density functional theory calculations and diffuse reflectance spectroscopy demonstrated that depending on the π-π-interaction and TTFTC˙+ population, these MOFs enjoyed varying degrees of TTFTC/TTFTC˙+ intervalence charge transfer (IVCT) interactions, which commensurately affected their electronic and optical band gaps and electrical conductivity. Having the shortest d π-π (3.39 Å) and the largest initial TTFTC˙+ population (∼23%), the oxidized Na-MOF 1-ox displayed the narrowest band gap (1.33 eV) and the highest room temperature electrical conductivity (3.6 × 10-5 S cm-1), whereas owing to its longest d π-π (3.68 Å) and a negligible TTFTC˙+ population, neutral Cs-MOF 4 exhibited the widest band gap (2.15 eV) and the lowest electrical conductivity (1.8 × 10-7 S cm-1). The freshly prepared but not optimally oxidized K-MOF 2 and Rb-MOF 3 initially displayed intermediate band gaps and conductivity, however, upon prolonged aerobic oxidation, which raised the TTFTC˙+ population to saturation levels (∼25 and 10%, respectively), the resulting 2-ox and 3-ox displayed much narrower band gaps (∼1.35 eV) and higher electrical conductivity (6.6 × 10-5 and 4.7 × 10-5 S cm-1, respectively). The computational studies indicated that charge movement in these MOFs occurred predominantly through the π-stacked ligands, while the experimental results displayed the combined effects of π-π-interactions, TTFTC˙+ population, and TTFTC/TTFTC˙+ IVCT interaction on their electronic and optical properties, demonstrating that IVCT interactions between the mixed-valent ligands could be exploited as an effective design strategy to develop electrically conducting MOFs.

Electrically Conductive 3D Metal-Organic Framework Featuring π-Acidic Hexaazatriphenylene Hexacarbonitrile Ligands with Anion-π Interaction and Efficient Charge-Transport Capabilities.

Semiconducting metal-organic frameworks (MOFs) show great potential to foster myriad advanced electronics and energy technologies, but they must possess adequate charge-carrier concentration and efficient charge-transport pathways in order to display useful electrical conductivity. A new intrinsically conducting 3D framework [Ag2(HATHCN)(CF3SO3)2]n was constructed by employing a highly π-acidic 1,4,5,8,9,12-hexaazatriphenylene-2,3,6,7,10,11-hexacarbonitrile (HATHCN) ligand, which assumed a paramagnetic HATHCN•- radical anion character by acquiring electron density from the TfO- anions involved in the anion-π interaction and facilitated charge movement along the staircase-like [-Ag+-HATHCN-]∞ chains having ample Ag4d+-N2p orbital overlap in the valence band region. As a result, the MOF displayed a narrow band gap (1.35 eV) and promising electrical conductivity (7.3 × 10-4 S/cm, 293 K) that ranked very high among those recorded for 3D MOFs. This work presents a new strategy to construct intrinsically conductive 3D frameworks by exploiting the dual metal coordination and anion-π interaction capabilities of a highly π-acidic HATHCN ligand.

The Advent of Electrically Conducting Double-Helical Metal-Organic Frameworks Featuring Butterfly-Shaped Electron-Rich π-Extended Tetrathiafulvalene Ligands.

To diversify metal-organic framework (MOF) structures beyond traditional Euclidean geometries and to create new charge-delocalization pathways beneficial for electrical conductivity, we constructed a novel double-helical MOF (dhMOF) by introducing a new butterfly-shaped electron-rich π-extended tetrathiafulvalene ligand equipped with four benzoate groups (ExTTFTB). The face-to-face oriented convex ExTTFTB ligands connected by Zn2(COO)4 paddlewheel nodes formed ovoid cavities suitable for guest encapsulation, while π-π-interaction between the ExTTFTB ligands of neighboring strands helped create new charge-delocalization pathways in iodine-mediated partially oxidized dhMOF. Iodine vapor diffusion led to oxidation of half of the ExTTFTB ligands in each double-helical strand to ExTTFTB•+ radical cations, which putatively formed intermolecular ExTTFTB/ExTTFTB•+ π-donor/acceptor charge-transfer chains with the neutral ExTTFTB ligands of an adjacent strand, creating supramolecular wire-like charge-delocalization pathways along the helix seams. In consequence, the electrical conductivity of dhMOF surged from 10-8 S/m up to 10-4 S/m range after iodine treatment. Thus, the introduction of the electron-rich ExTTFTB ligand with a distinctly convex π-surface not only afforded a novel double-helical MOF architecture featuring ovoid cavities and unique charge-delocalization pathways but also, more importantly, delivered a new tool and design strategy for future development of electrically conducting stimuli-responsive MOFs.

Thiazolothiazole-Based Luminescent Metal-Organic Frameworks with Ligand-to-Ligand Energy Transfer and Hg2+-Sensing Capabilities.

Photoinduced electron and energy transfer through preorganized chromophore, donor, and acceptor arrays are key to light-harvesting capabilities of photosynthetic plants and bacteria. Mimicking the design principles of natural photosystems, we constructed a new luminescent pillared paddle wheel metal-organic framework (MOF), Zn2(NDC)2(DPTTZ), featuring naphthalene dicarboxylate (NDC) struts that served as antenna chromophores and energy donors and N,N'-di(4-pyridyl)thiazolo-[5,4-d]thiazole (DPTTZ) pillars as complementary energy acceptors and light emitters. Highly ordered arrangement and good overlap between the emission and absorption spectra of these two complementary energy donor and acceptor units enabled ligand-to-ligand Förster resonance energy transfer, allowing the MOF to display exclusively DPTTZ-centric blue emission (410 nm) regardless of the excitation of either chromophore at different wavelengths. In the presence of Hg2+, a toxic heavy metal ion, the photoluminescence (PL) of Zn2(NDC)2(DPTTZ) MOF underwent significant red-shift to 450 nm followed by quenching, whereas other transition metal ions (Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Cd2+) caused only fluorescence quenching but no shift. The free DPTTZ ligand also displayed similar, albeit less efficient, fluorescence changes, suggesting that the heavy atom effect and coordination of Hg2+ and other transition metal ions with the DPTTZ ligands were responsible for the fluorescence changes in the MOF. When exposed to a mixture of different metal ions, including Hg2+, the MOF still displayed the Hg2+-specific fluorescence signal, demonstrating that it could detect Hg2+ in the presence of other metal ions. The powder X-ray diffraction studies verified that the framework remained intact after being exposed to Hg2+ and other transition metal ions, and its original PL spectrum was restored upon washing. These studies demonstrated the light-harvesting and Hg2+ sensing capabilities of a new bichromophoric luminescent MOF featuring a seldom-used photoactive ligand, which will likely spark an explosion of TTZ-based MOFs for various optoelectronic applications in near future.

Efficient MOF-Sensitized Solar Cells Featuring Solvothermally Grown [100]-Oriented Pillared Porphyrin Framework-11 Films on ZnO/FTO Surfaces.

Owing to their abilities to assemble and organize a large number of redox and photoactive components in highly ordered periodic fashion, crystalline porous metal-organic frameworks (MOFs) have the potential to execute myriad complex functions, including charge transport and light to electrical energy conversion when the required conditions are fulfilled. Herein, we demonstrate an unprecedented spontaneous solvothermal growth of precisely [100]-oriented pillared porphyrin framework-11 (PPF-11) films featuring vertically aligned Zn-tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) walls and horizontally aligned 2,2'-dimethyl-4,4'-bipyridine beams attached to annealed ZnO-fluorine-doped tin oxide (FTO) surfaces and their remarkable photovoltaic performance in liquid-junction solar cells. The [100]-oriented PPF-11/ZnO-FTO photoanodes displayed excellent photovoltaic response (short-circuit current ( JSC): 4.65 mA/cm2, open-circuit voltage ( VOC): 470 mV, power conversion efficiency: 0.86%) that easily outperformed all control devices as well as previously reported porphyrin and Ru(bpy)32+-based visible light-harvesting MOFs with 10-1000 times greater photocurrent density and 2-375 times higher efficiency. The superior photovoltaic behavior of [100]-oriented PPF-11/ZnO films compared to epitaxially grown MOF thin films on insulating self-assembled monolayers and drop-cast PPF films with different orientations can be attributed to several factors, including better charge separation, transport, and injection capabilities of the former. The noncatenated PPF-11 was able to host electron-deficient C60 guests, filling in nearly half of its cavities and engage them in ZnTCPP/C60 charge-transfer interaction. However, the C60-doped PPF-11/ZnO films displayed much weaker photovoltaic response than undoped [100]-oriented PPF-11/ZnO films presumably due to exclusion of I-/I3- electrolyte from the C60-occupied cavities and the inability of isolated C60 guests to support long-range charge movement.

Cation-Assisted Reversible Folding and Anion Binding by a Naphthalenediimide-Based Ditopic Ion-Pair Receptor.

A novel heteroditopic ion-pair receptor was synthesized by tethering two π-acidic naphthalenediimide units with a tridentate bisimine linker. Upon chelating a ZnII or CdII ion with the linker, it adopts a U-conformation allowing the parallel NDI arms to sandwich charge-diffuse anions, and two such folded receptor molecules interlock with each other forming an [R3·MII·R3·X-] ion-pair complex. Extraction of the guest cation with a tetraazacrown ether returns the receptor to its original unfolded form.

Structural and Optical Properties of Nanocrystalline TiO2 with Multiwalled Carbon Nanotubes and Its Photovoltaic Studies Using Ru(II) Sensitizers.

In this study, the in situ sol-gel method has been deployed to prepare the titanium dioxide/multiwalled carbon nanotubes (TiO2/MWCNTs) nanocomposite (NCs) powders with varying content of MWCNTs (0.01-1.0 wt %), to construct the dye-sensitized solar cells (DSSCs). First, binder-free NCs were deposited on a transparent-conducting F:SnO2 (FTO) glass substrate by a doctor-blade technique and then anchored with Ru(II)-based dyes to either N719 or ruthenium phthalocyanine (RuPc). The structural and optical properties and interconnectivity of the materials within the composite are investigated thoroughly by various spectral techniques (XRD, XPS, Raman, FT-IR, and UV-vis), electron microscopy (HRTEM), and BET analysis. The experimental results suggest that the ratio of MWCNTs and TiO2 in NCs, morphology, and their interconnectivity influenced their structural, optical, and photovoltaic properties significantly. Finally, the photovoltaic performances of the assembled DSSCs with different content of MWCNTs to TiO2 films anchored with two different dyes were tested under one sun irradiation (100 mW/cm2). The measured current-voltage (IV) curve and incident photon-to-current conversion efficiency (IPCE) spectra of TiO2/0.1 wt % MWCNTs (T@0.1 C) for N719 dye show three times more power conversion efficiency (η = 6.21%) which is opposed to an efficiency (η = 2.07%) of T@0.1 C for RuPc dye under the same operating conditions.

Lowering Band Gap of an Electroactive Metal-Organic Framework via Complementary Guest Intercalation.

A new honeycomb-shaped electroactive metal-organic framework (MOF) has been constructed from an electron deficient naphthalenediimide (NDI) ligand equipped with two terminal salicylic acid groups. π-Intercalation of electron-rich planar tetrathiafulvalene (TTF) guests between the NDI ligands stacked along the walls lowers the electronic band gap of the material by ca. 1 eV. An improved electron delocalization through the guest-mediated π-donor/acceptor stacks is attributed to the diminished band gap of the doped material, which forecasts an improved electrical conductivity.

Fluoride-induced reduction of Ag(I) cation leading to formation of silver mirrors and luminescent Ag-nanoparticles.

In aprotic solvents, Lewis basic F(-) anion reduces Lewis acidic Ag(I) cation to Ag(0), forming metallic silver mirrors on the inner surfaces of reaction vessels and luminescent Ag-nanoparticles (AgNPs) in supernatant solutions, which emit blue light upon UV irradiation. The F(-)-induced formation of silver mirrors and AgNPs was confirmed through X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), fluorescence spectroscopy, and mass spectrometry, whereas the Ag(I)-induced oxidation of F(-) to F radical, followed by its conversion to HF2(-) via H-abstraction and H-bonding, was evident from (19)F NMR spectroscopy. This redox reaction is deactivated in water, as the reducing power of hydrated F(-) diminishes drastically. Less Lewis basic Cl(-), Br(-), and I(-) ions do not reduce Ag(I) to Ag(0), instead they can only form Ag(I) halide precipitates irrespective of protic or aprotic solvents. The Ag-coated surfaces, luminescent AgNPs, and F radicals produced by this unprecedented redox reaction could be exploited as electrodes, light-emitting materials, and radical initiators, respectively.

Dye-sensitized solar cells based on multichromophoric supramolecular light-harvesting materials.

Multichromophoric dye-sensitized solar cells (DSSCs) comprised of a supramolecular zinc-phthalocyanineperyleneimide (ZnPc···PMI) dyad convert light to electrical energy with much higher power conversion efficiency (PCE = 2.3%) and incident-photon-to-current-efficiency (IPCE = ca. 40%) than the devices made of individual dyes.

Anion-directed assembly of a non-interpenetrated square-grid metal-organic framework with nanoscale porosity.

A non-interpenetrated square grid metal-organic framework (MOF) comprised of octahedral Zn(II) ions and linear N,N'-di(4-pyridyl)-1,4,5,8-naphthalenediimide (DPNDI) ligands was formed in the presence of noncoordinating perchlorate counterions that occupied the cavities of the porous network by forming CH···anion hydrogen bonds with DPNDI ligands, whereas a linear coordination polymer was obtained when Zn(II)-coordinated nitrate ions were present as counterions.

Tunable electronic interactions between anions and perylenediimide.

Over the past decade anion-π interaction has emerged as a new paradigm of supramolecular chemistry of anions. Taking advantage of the electronic nature of anion-π interaction, we have expanded its boundaries to charge-transfer (CT) and formal electron transfer (ET) events by adjusting the electron-donating and accepting abilities of anions and π-acids, respectively. To establish that ET, CT, and anion-π interactions could take place between different anions and π-acids as long as their electronic and structural properties are conducive, herein, we introduce 3,4,9,10-perylenediimide (PDI-1) that selectively undergoes thermal ET from strong Lewis basic hydroxide and fluoride anions, but remains electronically and optically silent to poor Lewis basic anions, as ET and CT events are turned OFF. These interactions have been fully characterized by UV/Vis, NMR, and EPR spectroscopies. These results demonstrate the generality of anion-induced ET events in aprotic solvents and further refute a notion that strong Lewis basic hydroxide and fluoride ions can only trigger nucleophilic attack to form covalent bonds instead of acting as sacrificial electron donors to π-acids under appropriate conditions.

Controllable self-assembly of amphiphilic macrocycles into closed-shell and open-shell vesicles, nanotubes, and fibers.

Depending on functional groups, amphiphilic hexaamide macrocycles self-assemble into closed-shell and open-shell vesicles in polar solvents. In the presence of water, open-shell vesicles morph into closed-shell vesicles, whereas acidification of the medium transforms vesicles into nanotubes and fibers.

Multichromophoric dye-sensitized solar cells based on supramolecular zinc-porphyrin···perylene-imide dyads.

Multichromophoric dye-sensitized solar cells (DSCs) based on self-assembled zinc-porphyrin···peryleneimide dyads on TiO(2) films display more efficient light-to-electrical energy conversion than DSCs based on individual dyes. Higher efficiency of multichromophoric dyes can be attributed to co-sensitization as well as vectorial electron transfer that lead to better electron-hole separation in the device.

Microsecond dye regeneration kinetics in efficient solid state dye-sensitized solar cells using a photoelectrochemically deposited PEDOT hole conductor.

Microsecond dye-regeneration kinetics was observed in efficient solid state dye-sensitized solar cells using photoelectrochemically deposited poly(3,4-ethylenedioxythiophene (PEDOT) hole conductors using transient absorption spectroscopy. The dye-regeneration rate is orders of magnitude slower than the case using the I(-)/I(3)(-) redox couple or commonly used small molecule hole conductor and is attributed to the low dye to PEDOT ratio within the films.