Stochastic Sensing of Chloride Anions Using an α-Hemolysin Pore with semiaza-Bambusuril Adapter.

Pores containing molecular adapters provide internal selective binding sites, thereby allowing the stochastic sensing of analytes. Herein, we demonstrate that semiaza-bambusuril (BU) acts as a non-covalent molecular adapter when lodged within the lumen of the wild-type α-hemolysin (WT-αHL) protein pore. Because the bambusurils are recognized as anion receptors, the anion binding site within the adapter-nanopore complex allows the detection of chloride anions, thus converting a non-selective pore into an anion sensor.

Selective Perchlorate Sensing Using Electrochemical Impedance Spectroscopy with Self-Assembled Monolayers of semiaza-Bambusurils.

In the last two decades, perchlorate salts have been identified as environmental pollutants and recognized as potential substances affecting human health. We describe self-assembled monolayers (SAMs) of novel semiaza-bambus[6]urils (semiaza-BUs) equipped with thioethers or disulfide (dithiolane) functionalities as surface-anchoring groups on gold electrodes. Cyclic voltammetry (CV) with Fe(CN)6 3-/4- as a redox probe, together with X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and ellipsometry, were employed to characterize the interactions at the interface between the anchoring groups and the metal substrate. Data showed that the anion receptors' packing on the gold strongly depends on the anchoring group. As a result, SAMs of BUs with lipoic amide side chains show a concentration-dependent layer thickness. The BU SAMs are extremely stable on repeated electrochemical potential scans and can selectively recognize perchlorate anions. Our electrochemical impedance spectroscopy (EIS) studies indicated that semiaza-BU equipped with the lipoic amide side chains binds perchlorate (2-100 mM) preferentially over other anions such as F- , Cl- , I- , AcO- , H2 PO4 - , HPO4 2- , SO4 2- , NO2 - , NO3 - , or CO3 2- . The resistance performance is 10 to 100 times more efficient than SAMs containing all other tested anions.

semiaza-Bambusurils are anion-specific transmembrane transporters.

semiaza-Bambus[6]urils efficiently transport anions across lipid membranes. A systematic modification of their lipophilic side chains to include various alkyl groups and thioethers reveals that the most efficient chloride transporters are those that agree with Lipinski's rule-of-lipophilicity, exhibiting clog Po/w values close to 5. Furthermore, vesicle anion-transport assays show that the new anion-transporters are independent of the cation identity but exhibit high anion selectivity, NO3- > Br- > Cl- > SO42-, in agreement with the Hofmeister series. These findings will allow for the design of highly specific anion transporters for biomedical applications, particularly for managing anion channelopathies.

Metal-Free Supramolecular Catalytic Hydrolysis of Ammonia Borane through Cucurbituril Nanocavitands.

Ammonia borane (AB) is considered a potential "on-board" hydrogen storage material. However, its implementation as a hydrogen reservoir in fuel cells is lacking due to the extremely slow release of hydrogen at room-temperature hydrolysis. In this study, a metal-free supramolecular strategy is demonstrated at room temperature to increase the hydrolysis rate and yield of hydrogen along with significant reduction in ammonia release by using cucurbit[5/8]uril (CB5/CB8) nanocavitands as catalysts. The complex of AB with CB stabilizes the ammonium ion at the host portals, which reduces ammonia release and enhances hydrogen yield. The complexation brings down the activation energy of hydrolysis from 103.8 to ∼27.5 kJ mol-1 (for CB5), a value close to the Pt/Pd nanoparticle-based catalysts reported so far. The high catalytic performance and reusability of CB catalysts at very low concentration make AB a promising supramolecular alternative for a sustainable "on-board" energy source.

Cooperative enhancement of antibacterial activity of sanguinarine drug through p-sulfonatocalix[6]arene functionalized silver nanoparticles.

The amelioration of antibacterial efficacy along with the reduced minimum inhibitory concentration (MIC) of sanguinarine (SGR) drug have been demonstrated through the uptake of SGR by p-sulfonatocalix[6]arene functionalized silver nanoparticles. The large upward pKa shift and enhanced stability of SGR resulting from the favorable supra-nanomolecular strategy are deciphered into an improved antibacterial drug against different pathogenic micro-organisms including multi drug resistant bacteria.

Redox-mediated Negative Differential Resistance (NDR) Behavior in Perylenediimide Derivative: A Supramolecular Approach.

Deaggregated perylenediimide (PDI) derivatives exhibit exceptionally high quantum yields, photostability and appropriate molecular features for organic electronics. This work demonstrates a metal-dye-metal framework with a large and stable negative differential resistance (NDR) at ambient conditions, built using a supramolecular strategy. The deaggregation achieved through the encapsulation of the bay-substituted phenyl groups of aggregated (l/d)-Phe-PDI dyes by the ß-CD macrocyclic host is validated through detailed spectroscopic and imaging techniques. The host-guest interaction resulted in a dramatic enhancement in the emission yield from 0.28 to 0.90. In the thin film deposits, the ß-CD/(l/d)-Phe-PDI complex displayed well-connected sheet-like morphology, whereas the uncomplexed (l/d)-Phe-PDI dye remained as scattered lumps. The large and reversible I-V characteristics displaying strong NDR behavior is attributed to the oxidation/reduction processes involving the rigid π-rich PDI core and is stable at least for about six months at ambient conditions, a promising system for organic electronics applications.

Supramolecular Assembly Induced Emission of Thiazole Orange with Sulfobutylether ß-cyclodextrin: A Stimuli-Responsive Fluorescence Sensor for Tyramine.

Modulation and control of stimuli responsive features of molecular assemblies in organized assemblies/cavitand macrocycles have received immense attention in many areas. In this study, we have established the formation of a discrete molecular assembly of thiazole orange (TO) dyes at the portals of the sulfobutylether ß-cyclodextrin (SBE7 ßCD) macrocycle leading to the evolution of a strong and distinct emission band from aggregated TO. The supramolecular assembly promoted portal aggregation of TO in its 1 : 4 (SBE7 ßCD : TO) composition, characterized by absorption, fluorescence, circular dichroism, ITC and 1 H NMR measurements, was probed to be selectively responsive to tyramine among other biogenic amines/neurotransmitters. For the first time, the different extent of emission quenching of SBE7 ßCD : TO assembly in the presence of biogenic amines/neurotransmitters is translated to achieve a selective on-off fluorescence sensor for the detection of tyramine against other neurotransmitters with a limit-of-detection (LOD) as low as ∼575 nM (79 ppb). The emission features of the assembly with changes in temperature is found to be highly reproducible even after several temperature cycles and is promising to design an optical supramolecular thermometer in the ambient temperature range.

Supramolecular Nanorods of (N-Methylpyridyl) Porphyrin With Captisol: Effective Photosensitizer for Anti-bacterial and Anti-tumor Activities.

Porphyrins, especially the 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin (TMPyP), are well-accepted as photosensitizers due to strong absorption from visible to near-infrared region, good singlet oxygen quantum yields as well as chemical versatility, all of which can be further modulated through planned supramolecular strategies. In this study, we report the construction of supramolecular nanorods of TMPyP dye/drug with captisol [sulfobutylether-ß-cyclodextrin (SBE7ßCD)] macrocycle through host-guest interaction. The availability of four cationic N-methylpyridyl groups favors multiple binding interaction with the captisol host, building an extended supramolecular assembly of captisol and TMPyP. In addition to the spectroscopic characterizations for the assembly formation, the same has been pictured in SEM and FM images as nanorods of ~10 µm in length or more. Complexation of TMPyP has brought out beneficial features over the uncomplexed TMPyP dye; enhanced singlet oxygen yield, improved photostability, and better photosensitizing effect, all supportive of efficient photodynamic therapy activity. The Captisol:TMPyP complex displayed enhanced antibacterial activity toward E. coli under white light irradiation as compared to TMPyP alone. Cell viability studies performed in lung carcinoma A549 cells with light irradiation documented increased cytotoxicity of the complex toward the cancer cells whereas reduced dark toxicity is observed toward normal CHO cells. All these synergistic effects of supramolecular nanorods of Captisol-TMPyP complex make the system an effective photosensitizer and a superior antibacterial and antitumor agent.

Ultra-Bright Rhodamines with Sulfobutylether-ß-Cyclodextrin: A Viable Supramolecular Dye Laser in Aqueous Medium.

Although aqueous dye lasers are much sought after, they have been of no practical use, as laser dyes show a strong tendency for aggregation in water, thus diminishing their optical output. Contributing towards this shortcoming, we studied the noncovalent interactions of two prominent laser dyes, namely, rhodamine 6G and rhodamine B, with a water soluble macrocyclic host, sulfobutylether-ß-cyclodextrin (SBE7 ßCD). Spectral changes in the absorption and fluorescence behavior of dyes in presence of the SBE7 ßCD host indicated adequate complex formation between dye and host (K∼104  M-1 ). A combination of various photophysical parameters evaluated from measurements such as Job plot, changes in the fluorescence lifetime/anisotropy values, and favorable thermodynamic parameters from isothermal titration calorimetric measurements adjudicated a 1 : 1 stoichiometric complex formation between dye and SBE7 ßCD host. Consequently, SBE7 ßCD prevents dye aggregation/adsorption and present rhodamine dyes in their monomeric forms with enhanced fluorescence yield and brightness. These vital parameters were utilized to optimize and demonstrate cost-effective supramolecular broad-band and narrow-band aqueous dye laser systems with improved lasing efficiencies (∼25 % higher for the SBE7 ßCD : RhB system and ∼10 % higher for SBE7 ßCD : Rh6G system), better beam profile, and enhanced durability compared to the respective dyes in optically matched ethanol solutions.

pH-responsive molecular assemblies of pyridylbutadiene derivative with cucurbit[7]uril.

The interaction between red-emitting pyridinium derivative [4-((1E,3E)-4-(4-(dimethylamino)phenyl)buta-1,3-dien-1-yl)-1-methylpyridin-1-ium] (DABP) and cucurbit[7]uril was investigated using optical absorption, steady-state and time-resolved fluorescence and anisotropy measurements. The changes in the UV/Vis absorption, fluorescence spectral characteristics and lifetime, with a change in pH, reveal efficient binding of CB7 to the dye molecule. The cucurbit[7]uril encapsulated DABP brings ∼1.5 units upward pK a shift. The formation of supramolecular assemblies with 1 : 1 and 2 : 1 host-guest stoichiometries with CB7 at different pH conditions have been verified from 1H NMR, isothermal titration calorimetric studies and geometry optimization calculations. CB7-dye complexation and the ensuing morphological changes were revealed by SEM, AFM and optical microscopy images. This pH-responsive supramolecular assemblies of red-emitting DABP dye can find potential applications in biological imaging, optical pH-sensor and the construction of building blocks for the supramolecular architectures.

Stimuli-Responsive Cucurbit[7]uril-Mediated BSA Nanoassembly for Uptake and Release of Doxorubicin.

We report the construction of a non-toxic nanoassembly of bovine serum albumin (BSA) protein and the cucurbit[7]uril macrocycle as well as its stimuli-responsive breakage with adamantylamine or pH, which restores the protein structure and recognition properties. The assembly showed efficient loading and controlled release of a standard drug, doxorubicin (DOX), and the same was validated in live cells. The cell viability studies documented that the DOX-loaded assembly mask the cytotoxicity of DOX and the toxicity can be revived at the target on demand, triggering its therapeutic activation. This is found to be more effective in the cancer cells. In addition, such host-assisted protein assemblies are also highly promising for stabilizing/protecting the native protein structure, a viable approach to prevent/inhibit protein misfolding and aggregation.