Tunable Electrochemical Entropy through Solvent Ordering by a Supramolecular Host.

The objective of this project is to use solvophobic interactions to guide conformational changes of molecular containers constructed with cholic acid as a building block. This dissertation describes 1) conformationally controllable amphiphilic molecules with solvent-responsiveness and/or photo-responsiveness, and their applications as supramolecular hosts and catalysts, 2) inclusion compounds of βaminocholic acid with high guest/host (=4/1) ratio, and 3) an efficient synthetic method to make multivalent water-soluble calixarenes with click chemistry. Amphiphilic “molecular baskets” with multiple facially amphiphilic cholates could aggregate intramolecularly to form a micelle-like conformer in polar solvents and a reversed-micelle-like one in nonpolar solvents. The stability of the reversed micelle-like conformers were influenced by the preorganization of the scaffold, the difference in solvophobicity between the α and the β faces of the cholate, and the spacers between the cholates and the scaffold. Microphase-separation of solvents was found to occur within the baskets. The environmentally responsive baskets could act as a novel supramolecular host to bind hydrophilic guests in nonpolar solvent mixtures and hydrophobic guests in polar solvents. Solvent-responsiveness could be easily coupled with photoresponsiveness by the introduction of azobenzene-spacers. A porphyrin could be used as the scaffold as well. Binding studies of the basket with the Zn-porphyrin scaffold indicated that the conformational change could be utilized to tune the substrate-selectivity of the metalloporphyrin. The basket with a Fe-porphyrin scaffold could act as a solventtunable supramolecular catalyst.

Macrocycles up to 15 members with different heteroatoms (N, O, and S) and dendrimeric functionalized branches were assembled, resulting in unique "collective" supramolecular hosts with several active sites for transition metal ions complexation. The nature of the interactions between these kinds of systems and metal ions of the first transition series (Fe, Ni, Cu, Zn) was evaluated by calculations of the binding energies at the B3LYP/LACVP* level of theory, resulting in a preference of metal ions for macrocyclic cavity in terms of complexation; however, there is a favorable contribution in energy due to the cooperative effect of dendrimeric branches (DBs) in the inclusion process by means of long-range interactions between metal ions and the heteroatoms present in DBs. According to calculated binding energies, even when the complexation in the middle of DBs appears as a less favored situation, still competes with the complexation occurred in several known macrocycles traditionally used in the formation of inclusion complexes. The capability of macrocycles as host entities is related to some criteria like: (1) the compatibility in orbital symmetry between host and guest molecules; (2) the cavity dimensions and the negative charge inside; and (3) the hardness-softness affinity between host and guest molecules. When DBs are included in host systems, their flexibility seems to be very important, in addition to localized negative charge, which permits the occurrence of long-range interactions.

The metal complexes, [M(Hdammthiol)(2)]Cl·3H(2)O [M = Cr(III) (1), Fe(III) (2)] [where H(2)dammthiol is the thiol form of the ligand, diacetylmonoxime morpholine N-thiohydrazone] were synthesized by metal template reactions of diacetylemonoxime with morpholine N-thiohydrazide in the presence of CrCl(3)·6H(2)O and FeCl(3)·6H(2)O. Both the complexes (1 and 2) were characterized by single crystal X-ray crystallography, spectroscopic (IR and UV-vis), Mössbauer and TGA analyses. The single crystal X-ray studies of both complexes show that the supramolecular hosts, constructed by the discrete mononuclear complexes, form supramolecular channels along the c-axis which are filled up by water-chloride clusters. In both complexes, the 1D water-chloride chain with chair-like architecture within the supramolecular hosts presents novelty. The magnetic measurement study of Fe(III) complex shows a spin crossover from S = 1/2 at 2.5 K to S = 5/2 at 300 K. At very low temperature, the presence of strong cooperative hydrogen bonding interactions stabilizes the S = 1/2 state.

Crystal engineering of three-component crystals with guest-dependent photoluminescence switching, including (i) crystallization-induced emission enhancement, (ii) intermolecular charge-transfer emission, and (iii) room-temperature phosphorescence under ultraviolet irradiation, was demonstrated. This strategy was based on the confinement of aromatic guests in a supramolecular host (denoted as EBPDI-TPFB) composed of 5,5'-(ethyne-1,2-diyl)bis(2-pyridin-3-yl-isoindoline-1,3-dione (EBPDI) with two tris(pentafluorophenyl)borane (TPFB) molecules linked by B-N dative bonds that acted as Lewis pairs. The single-crystal X-ray structures of complexes with eight different guests were collected, revealing that the size and/or shape of the supramolecular host EBPDI-TPFB was modulated by the included guest molecules. The excellent guest inclusion ability of EBPDI-TPFB allowed systematic photoluminescence regulation of the complexes, which exhibited multicolor emissions in the crystalline state. Photoluminescence switching characteristics of the complexes were observed upon removing the guests or mechanical grinding of the crystals. These results indicated that using the host-guest chemistry of multicomponent crystals not only facilitates crystallization, but also can reveal hidden optical functions by combining molecules of interest, which should contribute to the fields of physical chemistry and materials science.

Host-guest interaction into the cage of a supramolecular iron-organic complex – Is the process enthalpically or entropically- driven?

Synchronous fluorescence based biosensor for albumin determination by cooperative binding of fluorescence probe in a supra-biomolecular host–protein assembly

The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescence-based method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host-dye reporter pair are encapsulated inside phospholipid vesicles. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host-dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.

New supramolecular complexes [(Me 3 Sn)(Ph 3 Sn) 2 Fe(CN) 6 ] (I) and [(n-Bu 3 Sn)(Ph 3 Sn) 2 Fe(CN) 6 ] (II) are readily accessible by straightforward self-assembly of [Fe(CN) 6 ] 3− and hydrated R 3 Sn+/R′ 3 Sn + ions (R = Ph, and R′ = Me or n-Bu). The structural characterization of (I) and (II) is compared with well-documented supramolecular complex containing only Ph 3 Sn + unit, [(Ph 3 Sn) 3 Fe(CN) 6 ]. These novel compounds have wide internal cavities capable of encapsulating voluminous organic compounds, and they behave as host acceptors forming charge transfer complexes (CTC). Thiophene compounds acting as guest donor species are encapsulated within the cavities of the three-dimensional (3D) supramolecular hosts. The structure and physical properties of these hosts and host–guest systems were studied by X-ray powder diffraction, IR, UV/Vis., and magnetic measurements.

Signal transductionmechanisms are key to living systems. Cellsrespond to signals by changing catalytic activity of enzymes. Thissignal responsive catalysis is crucial in the regulation of (bio)chemicalreaction networks (CRNs). Inspired by these networks, we report anartificial signal responsive system that shows signal-induced temporarycatalyst activation. We use an unstable signal to temporarily activatean out of equilibrium CRN, generating transient host–guestcomplexes to control catalytic activity. Esters with favorable bindingtoward the cucurbit[7]uril (CB[7]) supramolecular host are used astemporary signals to form a transient complex with CB[7], replacinga CB[7]-bound guest. The esters are hydrolytically unstable, generatingacids and alcohols, which do not bind to CB[7], leading to guest reuptake.We demonstrate the feasibility of the concept using signal-controlledtemporary dye release and reuptake. The same signal controlled systemwas then used to tune the reaction rate of aniline catalyzed hydrazoneformation. Varying the ester structure and concentration gave accessto different catalyst liberation times and free catalyst concentration,regulating the overall reaction rate. With temporary signal controlledtransient complex formation we can tune the kinetics of a second chemicalreaction, in which the signal does not participate. This system showspromise for building more complex nonbiological networks, to ultimatelyarrive at signal transduction in organic materials.

Dynamic regulation of chemical reactivity is important in many complex chemical reaction networks, such as cascade reactions and signal transduction processes. Signal responsive catalysts could play a crucial role in regulating these reaction pathways. Recently, supramolecular encapsulation was reported to regulate the activities of artificial catalysts. We present a host‐guest chemistry strategy to modulate the activity of commercially available synthetic organocatalysts. The molecular container cucurbit[7]uril was successfully applied to change the activity of four different organocatalysts and one initiator, enabling up‐ or down‐regulation of the reaction rates of four different classes of chemical reactions. In most cases CB[7] encapsulation results in catalyst inhibition, however in one case catalyst activation by binding to CB[7] was observed. The mechanism behind this unexpected behavior was explored by NMR binding studies and p K a measurements. The catalytic activity can be instantaneously switched during operation, by addition of either supramolecular host or competitive binding molecules, and the reaction rate can be predicted with a kinetic model. Overall, this signal responsive system proves a promising tool to control catalytic activity.

Cucurbit[7]uril (CB7), a supramolecular host, is employed to control the pathway of photolysis of an aryl azide in an aqueous medium. Normally, photolysis of aryl azides in bulk water culminates predominantly in the formation of azepine derivatives via intramolecular rearrangement. Remarkably, however, when this process unfolds within the protective confinement of the CB7 cavity, it results in a carboline derivative, as a consequence of a C─H amination reaction. The resulting carboline caged by CB7 reveals long-lived room temperature phosphorescence (RTP) in the solid state, with lifetimes extending up to 2.1 s. These findings underscore the potential of supramolecular hosts to modulate the photolysis of aryl azides and to facilitate novel phosphorescent materials.

Tetradentate bis(pyridyltriazole) ligands containing aromatic spacers of different sizes react with Cu(2+) to produce metallo-supramolecular hosts that bind 1,4-diazabicyclo[2.2.2]octane molecules internally.

A series of water insoluble poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] amphiphilic copolymers was synthesized and their solubility properties in the presence of different supramolecular host molecules were investigated. The resulting polymer-cavitand assemblies exhibited a thermoresponsive behavior that could be modulated by variation of the copolymer composition and length. Interestingly, the large number of hydrophobic nonyl units across the polymer chain induced the formation of kinetically-trapped nanoparticles in solution. These nanoparticles further agglomerate into larger aggregates at a temperature that is dependent on the polymer composition and the cavitand type and concentration. The present research expands the understanding on the supramolecular interactions between water insoluble copolymers and supramolecular host molecules.

Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.

A new and innovative class of calixarene-based polymers emerged as adsorbents for a variety of compounds and ions in solution and vapor media. These materials take advantage of the modifiable rims and hydrophobic cavities of the calixarene monomers, in addition to the porous nature of the polymeric matrix. With main-chain calixarenes' function as supramolecular hosts and the polymers' high surface areas, polycalixarenes can effectively encapsulate target analytes. This feature is particularly useful for environmental remediation as dangerous and toxic molecules reversibly bind to the macrocyclic cavity, which facilitates their removal and enables repeated use of the polymeric sorbent. This Spotlight touches on the unique characteristics of the calixarene monomers and discusses the synthetic methods of our reported calixarene-based porous polymers, including Sonogashira-Hagihara coupling, and diazo and imine bond formation. It then discusses the promising applications of these materials in adsorbing dyes, micropollutants, iodine, mercury, paraquat, and perfluorooctanoic acid (PFOA) from water. In most cases, these reports cover materials that outperform others in terms of recyclability, rates of adsorption, or uptake capacities of specific pollutants. Finally, this Spotlight addresses the current challenges and future aspects of utilizing porous polymers in pollution treatment.