Guest Encapsulation Alters the Thermodynamic Landscape of a Coordination Host.

The architecture of self-assembled host molecules can profoundly affect the properties of the encapsulated guests. For example, a rigid cage with small windows can efficiently protect its contents from the environment; in contrast, tube-shaped, flexible hosts with large openings and an easily accessible cavity are ideally suited for catalysis. Here, we report a "Janus" nature of a Pd6L4 coordination host previously reported to exist exclusively as a tube isomer (T). We show that upon encapsulating various tetrahedrally shaped guests, T can reconfigure into a cage-shaped host (C) in quantitative yield. Extracting the guest affords empty C, which is metastable and spontaneously relaxes to T, and the T⇄C interconversion can be repeated for multiple cycles. Reversible toggling between two vastly different isomers paves the way toward controlling functional properties of coordination hosts "on demand".

Disequilibrating azobenzenes by visible-light sensitization under confinement.

Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E-to-Z isomerization by using light of a desired color, including red. DESC relies on a combination of a macrocyclic host and a photosensitizer, which act together to selectively bind and sensitize E-azobenzenes for isomerization. The Z isomer lacks strong affinity for and is expelled from the host, which can then convert additional E-azobenzenes to the Z state. In this way, the host-photosensitizer complex converts photon energy into chemical energy in the form of out-of-equilibrium photostationary states, including ones that cannot be accessed through direct photoexcitation.

Photocleavable Anionic Glues for Light-Responsive Nanoparticle Aggregates.

Integrating light-sensitive molecules within nanoparticle (NP) assemblies is an attractive approach to fabricate new photoresponsive nanomaterials. Here, we describe the concept of photocleavable anionic glue (PAG): small trianions capable of mediating interactions between (and inducing the aggregation of) cationic NPs by means of electrostatic interactions. Exposure to light converts PAGs into dianionic products incapable of maintaining the NPs in an assembled state, resulting in light-triggered disassembly of NP aggregates. To demonstrate the proof-of-concept, we work with an organic PAG incorporating the UV-cleavable o-nitrobenzyl moiety and an inorganic PAG, the photosensitive trioxalatocobaltate(III) complex, which absorbs light across the entire visible spectrum. Both PAGs were used to prepare either amorphous NP assemblies or regular superlattices with a long-range NP order. These NP aggregates disassembled rapidly upon light exposure for a specific time, which could be tuned by the incident light wavelength or the amount of PAG used. Selective excitation of the inorganic PAG in a system combining the two PAGs results in a photodecomposition product that deactivates the organic PAG, enabling nontrivial disassembly profiles under a single type of external stimulus.

Supramolecular Semiconductivity through Emerging Ionic Gates in Ion-Nanoparticle Superlattices.

The self-assembly of nanoparticles driven by small molecules or ions may produce colloidal superlattices with features and properties reminiscent of those of metals or semiconductors. However, to what extent the properties of such supramolecular crystals actually resemble those of atomic materials often remains unclear. Here, we present coarse-grained molecular simulations explicitly demonstrating how a behavior evocative of that of semiconductors may emerge in a colloidal superlattice. As a case study, we focus on gold nanoparticles bearing positively charged groups that self-assemble into FCC crystals via mediation by citrate counterions. In silico ohmic experiments show how the dynamically diverse behavior of the ions in different superlattice domains allows the opening of conductive ionic gates above certain levels of applied electric fields. The observed binary conductive/nonconductive behavior is reminiscent of that of conventional semiconductors, while, at a supramolecular level, crossing the "band gap" requires a sufficient electrostatic stimulus to break the intermolecular interactions and make ions diffuse throughout the superlattice's cavities.

Altering the Properties of Spiropyran Switches Using Coordination Cages with Different Symmetries.

Molecular confinement effects can profoundly alter the physicochemical properties of the confined species. A plethora of organic molecules were encapsulated within the cavities of supramolecular hosts, and the impact of the cavity size and polarity was widely investigated. However, the extent to which the properties of the confined guests can be affected by the symmetry of the cage─which dictates the shape of the cavity─remains to be understood. Here we show that cage symmetry has a dramatic effect on the equilibrium between two isomers of the encapsulated spiropyran guests. Working with two Pd-based coordination cages featuring similarly sized but differently shaped hydrophobic cavities, we found a highly selective stabilization of the isomer whose shape matches that of the cavity of the cage. A Td-symmetric cage stabilized the spiropyrans' colorless form and rendered them photochemically inert. In contrast, a D2h-symmetric cage favored the colored isomer, while maintaining reversible photoswitching between the two states of the encapsulated spiropyrans. We also show that the switching kinetics strongly depend on the substitution pattern on the spiropyran scaffold. This finding was used to fabricate a time-sensitive information storage medium with tunable lifetimes of the encoded messages.

Ternary host-guest complexes with rapid exchange kinetics and photoswitchable fluorescence.

Confinement within molecular cages can dramatically modify the physicochemical properties of the encapsulated guest molecules, but such host-guest complexes have mainly been studied in a static context. Combining confinement effects with fast guest exchange kinetics could pave the way toward stimuli-responsive supramolecular systems-and ultimately materials-whose desired properties could be tailored "on demand" rapidly and reversibly. Here, we demonstrate rapid guest exchange between inclusion complexes of an open-window coordination cage that can simultaneously accommodate two guest molecules. Working with two types of guests, anthracene derivatives and BODIPY dyes, we show that the former can substantially modify the optical properties of the latter upon noncovalent heterodimer formation. We also studied the light-induced covalent dimerization of encapsulated anthracenes and found large effects of confinement on reaction rates. By coupling the photodimerization with the rapid guest exchange, we developed a new way to modulate fluorescence using external irradiation.

Polarization-sensitive optoionic membranes from chiral plasmonic nanoparticles.

Optoelectronic effects differentiating absorption of right and left circularly polarized photons in thin films of chiral materials are typically prohibitively small for their direct photocurrent observation. Chiral metasurfaces increase the electronic sensitivity to circular polarization, but their out-of-plane architecture entails manufacturing and performance trade-offs. Here, we show that nanoporous thin films of chiral nanoparticles enable high sensitivity to circular polarization due to light-induced polarization-dependent ion accumulation at nanoparticle interfaces. Self-assembled multilayers of gold nanoparticles modified with L-phenylalanine generate a photocurrent under right-handed circularly polarized light as high as 2.41 times higher than under left-handed circularly polarized light. The strong plasmonic coupling between the multiple nanoparticles producing planar chiroplasmonic modes facilitates the ejection of electrons, whose entrapment at the membrane-electrolyte interface is promoted by a thick layer of enantiopure phenylalanine. Demonstrated detection of light ellipticity with equal sensitivity at all incident angles mimics phenomenological aspects of polarization vision in marine animals. The simplicity of self-assembly and sensitivity of polarization detection found in optoionic membranes opens the door to a family of miniaturized fluidic devices for chiral photonics.

Coexistence of 1 : 1 and 2 : 1 inclusion complexes of indigo carmine.

We show that the optical properties of indigo carmine can be modulated by encapsulation within a coordination cage. Depending on the host/guest molar ratio, the cage can predominantly encapsulate either one or two dye molecules. The 1 : 1 complex is fluorescent, unique for an indigo dye in an aqueous solution. We have also found that binding two dye molecules stabilizes a previously unknown conformation of the cage.

Self-Complementary Zwitterionic Peptides Direct Nanoparticle Assembly and Enable Enzymatic Selection of Endocytic Pathways.

Supramolecular self-assembly in biological systems holds promise to convert and amplify disease-specific signals to physical or mechanical signals that can direct cell fate. However, it remains challenging to design physiologically stable self-assembling systems that demonstrate tunable and predictable behavior. Here, the use of zwitterionic tetrapeptide modalities to direct nanoparticle assembly under physiological conditions is reported. The self-assembly of gold nanoparticles can be activated by enzymatic unveiling of surface-bound zwitterionic tetrapeptides through matrix metalloprotease-9 (MMP-9), which is overexpressed by cancer cells. This robust nanoparticle assembly is achieved by multivalent, self-complementary interactions of the zwitterionic tetrapeptides. In cancer cells that overexpress MMP-9, the nanoparticle assembly process occurs near the cell membrane and causes size-induced selection of cellular uptake mechanism, resulting in diminished cell growth. The enzyme responsiveness, and therefore, indirectly, the uptake route of the system can be programmed by customizing the peptide sequence: a simple inversion of the two amino acids at the cleavage site completely inactivates the enzyme responsiveness, self-assembly, and consequently changes the endocytic pathway. This robust self-complementary, zwitterionic peptide design demonstrates the use of enzyme-activated electrostatic side-chain patterns as powerful and customizable peptide modalities to program nanoparticle self-assembly and alter cellular response in biological context.

Encapsulation within a coordination cage modulates the reactivity of redox-active dyes.

Confining molecules within well-defined nanosized spaces can profoundly alter their physicochemical characteristics. For example, the controlled aggregation of chromophores into discrete oligomers has been shown to tune their optical properties whereas encapsulation of reactive species within molecular hosts can increase their stability. The resazurin/resorufin pair has been widely used for detecting redox processes in biological settings; yet, how tight confinement affects the properties of these two dyes remains to be explored. Here, we show that a flexible PdII6L4 coordination cage can efficiently encapsulate both resorufin and resazurin in the form of dimers, dramatically modulating their optical properties. Furthermore, binding within the cage significantly decreases the reduction rate of resazurin to resorufin, and the rate of the subsequent reduction of resorufin to dihydroresorufin. During our studies, we also found that upon dilution, the PdII6L4 cage disassembles to afford PdII2L2 species, which lacks the ability to form inclusion complexes - a process that can be reversed upon the addition of the strongly binding resorufin/resazurin guests. We expect that the herein disclosed ability of a water-soluble cage to reversibly modulate the optical and chemical properties of a molecular redox probe will expand the versatility of synthetic fluorescent probes in biologically relevant environments.

Electrostatic co-assembly of nanoparticles with oppositely charged small molecules into static and dynamic superstructures.

Coulombic interactions can be used to assemble charged nanoparticles into higher-order structures, but the process requires oppositely charged partners that are similarly sized. The ability to mediate the assembly of such charged nanoparticles using structurally simple small molecules would greatly facilitate the fabrication of nanostructured materials and harnessing their applications in catalysis, sensing and photonics. Here we show that small molecules with as few as three electric charges can effectively induce attractive interactions between oppositely charged nanoparticles in water. These interactions can guide the assembly of charged nanoparticles into colloidal crystals of a quality previously only thought to result from their co-crystallization with oppositely charged nanoparticles of a similar size. Transient nanoparticle assemblies can be generated using positively charged nanoparticles and multiply charged anions that are enzymatically hydrolysed into mono- and/or dianions. Our findings demonstrate an approach for the facile fabrication, manipulation and further investigation of static and dynamic nanostructured materials in aqueous environments.

Morphology control in crystalline nanoparticle-polymer aggregates.

Self-assembly of nanoparticles can be mediated by polymers, but has so far led almost exclusively to nanoparticle aggregates that are amorphous. Here, we employed Coulombic interactions to generate a range of composite materials from mixtures of charged nanoparticles and oppositely charged polymers. The assembly behavior of these nanoparticle/polymer composites depends on their order of addition: polymers added to nanoparticles give rise to stable aggregates, but nanoparticles added to polymers disassemble the initially formed aggregates. The amorphous aggregates were transformed into crystalline ones by transiently increasing the ionic strength of the solution. The morphology of the resulting crystals depended on the length of the polymer: short polymer chains mediated the self-assembly of nanoparticles into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer assemblies, within which the crystalline order of nanoparticles was retained.

Light-Responsive Dynamic DNA-Origami-Based Plasmonic Assemblies.

DNA nanotechnology offers a versatile toolbox for precise spatial and temporal manipulation of matter on the nanoscale. However, rendering DNA-based systems responsive to light has remained challenging. Herein, we describe the remote manipulation of native (non-photoresponsive) chiral plasmonic molecules (CPMs) using light. Our strategy is based on the use of a photoresponsive medium comprising a merocyanine-based photoacid. Upon exposure to visible light, the medium decreases its pH, inducing the formation of DNA triplex links, leading to a spatial reconfiguration of the CPMs. The process can be reversed simply by turning the light off and it can be repeated for multiple cycles. The degree of the overall chirality change in an ensemble of CPMs depends on the CPM fraction undergoing reconfiguration, which, remarkably, depends on and can be tuned by the intensity of incident light. Such a dynamic, remotely controlled system could aid in further advancing DNA-based devices and nanomaterials.

Modulating the Optical Properties of BODIPY Dyes by Noncovalent Dimerization within a Flexible Coordination Cage.

Aggregation of organic molecules can drastically affect their physicochemical properties. For instance, the optical properties of BODIPY dyes are inherently related to the degree of aggregation and the mutual orientation of BODIPY units within these aggregates. Whereas the noncovalent aggregation of various BODIPY dyes has been studied in diverse media, the ill-defined nature of these aggregates has made it difficult to elucidate the structure-property relationships. Here, we studied the encapsulation of three structurally simple BODIPY derivatives within the hydrophobic cavity of a water-soluble, flexible PdII6L4 coordination cage. The cavity size allowed for the selective encapsulation of two dye molecules, irrespective of the substitution pattern on the BODIPY core. Working with a model, a pentamethyl-substituted derivative, we found that the mutual orientation of two BODIPY units in the cage's cavity was remarkably similar to that in the crystalline state of the free dye, allowing us to isolate and characterize the smallest possible noncovalent H-type BODIPY aggregate, namely, an H-dimer. Interestingly, a CF3-substituted BODIPY, known for forming J-type aggregates, was also encapsulated as an H-dimer. Taking advantage of the dynamic nature of encapsulation, we developed a system in which reversible switching between H- and J-aggregates can be induced for multiple cycles simply by addition and subsequent destruction of the cage. We expect that the ability to rapidly and reversibly manipulate the optical properties of supramolecular inclusion complexes in aqueous media will open up avenues for developing detection systems that operate within biological environments.

Molecular Photoswitching in Confined Spaces.

In nature, light is harvested by photoactive proteins to drive a range of biological processes, including photosynthesis, phototaxis, vision, and ultimately life. Bacteriorhodopsin, for example, is a protein embedded within archaeal cell membranes that binds the chromophore retinal within its hydrophobic pocket. Exposure to light triggers regioselective photoisomerization of the confined retinal, which in turn initiates a cascade of conformational changes within the protein, triggering proton flux against the concentration gradient, providing the microorganisms with the energy to live. We are inspired by these functions in nature to harness light energy using synthetic photoswitches under confinement. Like retinal, synthetic photoswitches require some degree of conformational flexibility to isomerize. In nature, the conformational change associated with retinal isomerization is accommodated by the structural flexibility of the opsin host, yet it results in steric communication between the chromophore and the protein. Similarly, we strive to design systems wherein isomerization of confined photoswitches results in steric communication between a photoswitch and its confining environment. To achieve this aim, a balance must be struck between molecular crowding and conformational freedom under confinement: too much crowding prevents switching, whereas too much freedom resembles switching of isolated molecules in solution, preventing communication.In this Account, we discuss five classes of synthetic light-switchable compounds-diarylethenes, anthracenes, azobenzenes, spiropyrans, and donor-acceptor Stenhouse adducts-comparing their behaviors under confinement and in solution. The environments employed to confine these photoswitches are diverse, ranging from planar surfaces to nanosized cavities within coordination cages, nanoporous frameworks, and nanoparticle aggregates. The trends that emerge are primarily dependent on the nature of the photoswitch and not on the material used for confinement. In general, we find that photoswitches requiring less conformational freedom for switching are, as expected, more straightforward to isomerize reversibly under confinement. Because these compounds undergo only small structural changes upon isomerization, however, switching does not propagate into communication with their environment. Conversely, photoswitches that require more conformational freedom are more challenging to switch under confinement but also can influence system-wide behavior.Although we are primarily interested in the effects of geometric constraints on photoswitching under confinement, additional effects inevitably emerge when a compound is removed from solution and placed within a new, more crowded environment. For instance, we have found that compounds that convert to zwitterionic isomers upon light irradiation often experience stabilization of these forms under confinement. This effect results from the mutual stabilization of zwitterions that are brought into close proximity on surfaces or within cavities. Furthermore, photoswitches can experience preorganization under confinement, influencing the selectivity and efficiency of their photoreactions. Because intermolecular interactions arising from confinement cannot be considered independently from the effects of geometric constraints, we describe all confinement effects concurrently throughout this Account.

Light-Driven Proton Transfer for Cyclic and Temporal Switching of Enzymatic Nanoreactors.

Temporal activation of biological processes by visible light and subsequent return to an inactive state in the absence of light is an essential characteristic of photoreceptor cells. Inspired by these phenomena, light-responsive materials are very attractive due to the high spatiotemporal control of light irradiation, with light being able to precisely orchestrate processes repeatedly over many cycles. Herein, it is reported that light-driven proton transfer triggered by a merocyanine-based photoacid can be used to modulate the permeability of pH-responsive polymersomes through cyclic, temporally controlled protonation and deprotonation of the polymersome membrane. The membranes can undergo repeated light-driven swelling-contraction cycles without losing functional effectiveness. When applied to enzyme loaded-nanoreactors, this membrane responsiveness is used for the reversible control of enzymatic reactions. This combination of the merocyanine-based photoacid and pH-switchable nanoreactors results in rapidly responding and versatile supramolecular systems successfully used to switch enzymatic reactions ON and OFF on demand.

Improving Fatigue Resistance of Dihydropyrene by Encapsulation within a Coordination Cage.

Photochromic molecules undergo reversible isomerization upon irradiation with light at different wavelengths, a process that can alter their physical and chemical properties. For instance, dihydropyrene (DHP) is a deep-colored compound that isomerizes to light-brown cyclophanediene (CPD) upon irradiation with visible light. CPD can then isomerize back to DHP upon irradiation with UV light or thermally in the dark. Conversion between DHP and CPD is thought to proceed via a biradical intermediate; bimolecular events involving this unstable intermediate thus result in rapid decomposition and poor cycling performance. Here, we show that the reversible isomerization of DHP can be stabilized upon confinement within a PdII6L4 coordination cage. By protecting this reactive intermediate using the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product obtainable from traditionally low-yielding organic reactions.

Molecular Factors Controlling the Isomerization of Azobenzenes in the Cavity of a Flexible Coordination Cage.

Photoswitchable molecules are employed for many applications, from the development of active materials to the design of stimuli-responsive molecular systems and light-powered molecular machines. To fully exploit their potential, we must learn ways to control the mechanism and kinetics of their photoinduced isomerization. One possible strategy involves confinement of photoresponsive switches such as azobenzenes or spiropyrans within crowded molecular environments, which may allow control over their light-induced conversion. However, the molecular factors that influence and control the switching process under realistic conditions and within dynamic molecular regimes often remain difficult to ascertain. As a case study, here we have employed molecular models to probe the isomerization of azobenzene guests within a Pd(II)-based coordination cage host in water. Atomistic molecular dynamics and metadynamics simulations allow us to characterize the flexibility of the cage in the solvent, the (rare) guest encapsulation and release events, and the relative probability/kinetics of light-induced isomerization of azobenzene analogues in these host-guest systems. In this way, we can reconstruct the mechanism of azobenzene switching inside the cage cavity and explore key molecular factors that may control this event. We obtain a molecular-level insight on the effects of crowding and host-guest interactions on azobenzene isomerization. The detailed picture elucidated by this study may enable the rational design of photoswitchable systems whose reactivity can be controlled via host-guest interactions.

Chemical reactivity under nanoconfinement.

Confining molecules can fundamentally change their chemical and physical properties. Confinement effects are considered instrumental at various stages of the origins of life, and life continues to rely on layers of compartmentalization to maintain an out-of-equilibrium state and efficiently synthesize complex biomolecules under mild conditions. As interest in synthetic confined systems grows, we are realizing that the principles governing reactivity under confinement are the same in abiological systems as they are in nature. In this Review, we categorize the ways in which nanoconfinement effects impact chemical reactivity in synthetic systems. Under nanoconfinement, chemical properties can be modulated to increase reaction rates, enhance selectivity and stabilize reactive species. Confinement effects also lead to changes in physical properties. The fluorescence of light emitters, the colours of dyes and electronic communication between electroactive species can all be tuned under confinement. Within each of these categories, we elucidate design principles and strategies that are widely applicable across a range of confined systems, specifically highlighting examples of different nanocompartments that influence reactivity in similar ways.