Self-assembled Coordination Cages Research Articles

Physical Isolation of Single Protein Molecules within Well-Defined Coordination Cages to Enhance Their Stability.

Encapsulation of a single protein within a confined space can lead to distinct properties compared to bulk solutions, but controlling the number of encapsulated proteins and their environment remains challenging. This study demonstrates the encapsulation of single proteins within well-defined, tunable cavities of self-assembled coordination cages, thereby enhancing protein stability. Within uniform cavities of size-tunable coordination cages, 15 different proteins of varying sizes (3-6 nm in diameter) and properties (e.g., isoelectric points and hydrophobicity) were successfully confined. Various analytical techniques confirmed that the proteins maintained their secondary structures and enzymatic activities under denaturing conditions such as exposure to organic solvents, heat, and buffers. These findings suggest that such coordination cages have the potential to serve as synthetic hosts for precisely controlling protein functions within their customizable cavities.

N-Heteroatom Engineered Nonporous Amorphous Self-Assembled Coordination Cages for Capture and Storage of Iodine.

Radioactive iodine isotopes from nuclear-related activities, present substantial risks to human health and the environment. Developing effective materials for the capture and storage of these hazardous molecules is paramount. Traditionally, nonporous solids were historically considered ineffective for adsorbing target species. In this study, we investigate the potential of four nonporous, amorphous, self-assembled coordination cages (C1, C2, C3, and C4) featuring varying numbers of nitrogen atoms within the core (pyridyl/triazine unit) and specific cavity sizes for iodine adsorption. These coordination cages demonstrate remarkable adsorption abilities for iodine in both vapor and solution phases, facilitated by enhanced electron-pair interactions. The cages exhibit high uptake capacities of up to 3.16 g g-1 at 75 °C, the highest among metal-organic cages and up to 434.29 mg g-1 in solution, highlighting the efficiency of these materials across different phases. Even at ambient temperature, they show significant iodine capture efficiency, with a maximum value of 1.5 g g-1. Furthermore, these robust materials can be recycled, enduring at least five reusable cycles without apparent fatigue. Overall, our findings present a "N-heteroatom engineering" approach for the development of recyclable amorphous containers for the capture and storage of iodine, contributing to the mitigation of nuclear-related risks.

Chiral Induction in a Self-Assembled Pd4 Coordination Cage with Chiral Guests.

The dynamic interplay of coordination bonds within metal-organic cages offers a unique avenue for structural evolution in response to external stimuli, presenting a promising strategy for the construction of chiral assemblies. This adaptability is crucial for the selective synthesis of homochiral assemblies and advancement of asymmetric catalysis. In this study, we report the self-assembly of an achiral square-planar Pd(II) acceptor with a C2-symmetric tetrapyridyl donor resulted in the formation of a racemic mixture of the chiral octahedral cage Pd4L2. The existence of this racemic mixture was confirmed using circular dichroism spectroscopy as well as single crystal X-ray diffraction analysis. We encoded chiral information into the asymmetric cavity of the cage by encapsulating chiral aromatic guests through efficient π-π stacking and hydrophobic interactions in aqueous media. The inclusion of a chiral guest induces a preference for one enantiomeric conformation of the cage over the other, effectively shifting the equilibrium towards a single, enantiopure host-guest complex. While the concept of chiral guest recognition by a chiral host is well-established, this work constitutes a remarkable example of guest-mediated chirality transfer leading to the formation of a single enantiopure coordination complex from achiral building blocks.

Cage-To-Cage Transformations in Self-Assembled Coordination Cages Using "Acid/Base" or "Guest Binding-Induced Strain" as Stimuli.

Controlling supramolecular systems between different functional forms by utilizing acids/bases as stimuli is a formidable challenge, especially where labile coordination bonds are involved. A pair of acid/base responsive, interconvertible 1,5-enedione/pyrylium based Pd2L4-type cages are prepared that exhibit differential guest binding abilities towards disulfonates of varied sizes. A three-state switch has been achieved, where (i) a weakly coordinating base induced cage-to-cage transformation in the first step, (ii) a strongly coordinating base triggered cage disassembly as the second step, and (iii) the third step shows acid(strong) promoted generation of initial cage, thereby completing the cycle. To our surprise, binding of a specific disulfonate guest facilitated cage-to-cage transformations by inducing strain on the cage assembly thereby opening the labile pyrylium rings of the cage. Through a competitive guest binding study, we demonstrated the superior guest binding capability of the octacationic pyrylium-based cage over a similar-sized tetracationic cage. These results provide a reliable approach to reversibly modulate the guest binding properties of acid/base-responsive self-assembled coordination cages.

Distinct selectivity inside self-assembled coordination cages.

Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a guest molecule(s) with a certain orientation and conformation. In this review, we try to illustrate how self-assembled coordination cages could achieve this goal. Two representative cage hosts, namely, self-assembled Pd(II)-ligand octahedral coordination cages ([Pd6L4]12+) and self-assembled Ga(III)-ligand tetrahedral coordination cages ([Ga4L6]12-) are selected as the pilot hosts that this mini review covers. Representative works in this area are presented here in brief.

Programmable Monodisperse Glyco-Multivalency Using Self-Assembled Coordination Cages as Scaffolds.

The multivalent presentation of glycans leads to enhanced binding avidity to lectins due to the cluster glycoside effect. Most materials used as scaffolds for multivalent glycan arrays, such as polymers or nanoparticles, have intrinsic dispersity: meaning that in any sample, a range of valencies are presented and it is not possible to determine which fraction(s) are responsible for binding. The intrinsic dispersity of many multivalent glycan scaffolds also limits their reproducibility and predictability. Here we make use of the structurally programmable nature of self-assembled metal coordination cages, with polyhedral metal-ion cores supporting ligand arrays of predictable sizes, to assemble a 16-membered library of perfectly monodisperse glycoclusters displaying valencies from 2 to 24 through a careful choice of ligand/metal combinations. Mono- and trisaccharides are introduced into these clusters, showing that the synthetic route is tolerant of biologically relevant glycans, including sialic acids. The cluster series demonstrates increased binding to a range of lectins as the number of glycans increases. This strategy offers an alternative to current glycomaterials for control of the valency of three-dimensional (3-D) glycan arrays, and may find application across sensing, imaging, and basic biology.

A Template-Free Pd2 L4 Cage with up to Nanomolar Affinity for Chloride in Aqueous Solutions.

Invited for the cover of this issue is the group of Dillip Kumar Chand at the Indian Institute of Technology Madras. The image depicts the efficient chloride binding ability of a designer self-assembled coordination cage in water. The binding occurs selectively even in presence of models of biologically abundant anionic systems. Read the full text of the article at 10.1002/chem.202300891.

Front Cover: A Template‐Free Pd2L4 Cage with up to Nanomolar Affinity for Chloride in Aqueous Solutions (Chem. Eur. J. 33/2023)

A supramolecular halide catcher catches chloride exclusively from an aqueous solution containing the biologically most abundant essential anions. Multiple noncovalent interactions are involved in the deep enclosure of the designer self-assembled coordination cage for chloride binding. Impressively, chloride is captured with up to nanomolar affinity in aqueous solutions. More information can be found in the Research Article by D. K. Chand and co-workers (DOI: 10.1002/chem.202300891).

Nonaqueous Emulsion Polycondensation Enabled by a Self-Assembled Cage-like Surfactant.

Nonaqueous emulsions are crucial for a range of applications based on water‐sensitive systems such as controlled polymerizations requiring anhydrous reaction conditions and the stabilization of readily hydrolyzable reagents or pharmacologically active components. However, defined molecular surfactants to stabilize such nonaqueous emulsions are scarce. We introduce a self‐assembled coordination cage, decorated with cholesterol functionalities, to serve as a molecular surfactant for various oil‐in‐oil emulsions of immiscible organic solvents. While the positively charged cage forms the amphiphile's polar moiety, the non‐polar cholesterol appendices can bend in a common direction to stabilize the emulsion. Templated by the droplets, polycondensation reactions were carried out to produce microstructured polyurethane and polyurea materials of different particle sizes and morphologies. Further, the amphiphilic cage can encapsulate a guest molecule and the resulting host‐guest assembly was also examined as a surfactant. In addition, the aggregation behavior of the amphiphilic cage in an aqueous medium was examined.

Photoinduced host-to-guest electron transfer in a self-assembled coordination cage.

A [Pd2L4] coordination cage, assembled from electron-rich phenothiazine-based ligands and encapsulating an electron-deficient anthraquinone-based disulfonate guest, is reported. Upon excitation at 400 nm, transient absorption spectroscopy unveils photoinduced electron transfer from the host's chromophores to the guest, as indicated by characteristic spectral features assigned to the oxidized donor and reduced acceptor. The structure of the host-guest complex was characterized by NMR spectroscopy, mass spectrometry and single-crystal X-ray analysis. Spectroelectrochemical experiments and DFT calculations both agree with the proposed light-induced charge separation. A kinetic analysis of the involved charge transfer channels reveals, besides a guest-independent LMCT path, 44% efficiency for the host-guest charge transfer (HGCT).

A self-assembled coordination cage enhances the reactivity of confined amides via mechanical bond-twisting.

Self-assembled coordination cages composed of metal cations and ligands can enhance the hydrolysis of non-covalently trapped amides in mild conditions as demonstrated in recent experiments. Here, we reveal the mechanism that accelerates base-catalyzed amide hydrolysis inside the octahedral coordination cage, by means of a quantum mechanics/molecular mechanics/polarizable continuum model. The calculated activation barrier of the nucleophilic OH- addition to a planar diaryl amide drastically decreases in the cage because of mechanical bond-twisting due to host-guest π-stacking. By contrast, the OH- addition to an N-acylindole, which possesses a twisted amide bond in bulk water, is not enhanced in the cage. Even though the cage hinders OH- collisions with the confined amide, the cage can twist the dihedral angle of the planar amide so as to mimic the transition state of OH- addition.

Controlling the Complexity and Interconversion Mechanisms in Self-Assembled [Fe2 L3 ]4+ Helicates and [Fe4 L6 ]8+ Cages.

Self-assembled coordination cages and metal-organic frameworks have relied extensively on symmetric ligands in their formation. Here we have prepared a relatively simple system employing an unsymmetric ligand that results in two distinct self-assembled structures, a [Fe2 L3 ]4+ helicate and a [Fe4 L6 ]8+ cage composed of 10 interconverting diastereomers and their enantiomers. We show that the steric profile of the ligand controls the complexity, thermodynamics and kinetics of interconversion of the system.

Molecular Confinement Effects by Self-Assembled Coordination Cages

Abstract When substrates are confined in an isolated cavity, they experience circumstances that are distinctly different from those in a bulk solution. Molecular self-assembly has widened the potential of molecular confinement by offering synthetic cavities on the nanometer-scale and allowing chemists to treat molecular aggregates and larger molecules in the cavities. In this account, we introduce the molecular confinement effects of self-assembled cages as a strategy to discover new or hidden properties and reactivities from the confined substrates in the cages. By confining molecules, the cavity can gather, arrange, fold, compress, and twist the molecules. The molecular confinement thus becomes a powerful strategy to draw new aspects of molecules.

Long-Lived C60 Radical Anion Stabilized Inside an Electron-Deficient Coordination Cage.

Fullerene C60 and its derivatives are widely used in molecular electronics, photovoltaics, and battery materials, because of their exceptional suitability as electron acceptors. In this context, single-electron transfer on C60 generates the C60• - radical anion. However, the short lifetime of free C60• - hampers its investigation and application. In this work, we dramatically stabilize the usually short-lived C60• - species within a self-assembled M2L4 coordination cage consisting of a triptycene-based ligand and Pd(II) cations. The electron-deficient cage strongly binds C60 by providing a curved inner π-surface complementary to the fullerene's globular shape. Cyclic voltammetry revealed a positive potential shift for the first reduction of encapsulated C60, which is indicative of a strong interaction between confined C60• - and the cationic cage. Photochemical one-electron reduction with 1-benzyl-1,4-dihydronicotinamide allows selective and quantitative conversion of the confined C60 molecule in millimolar acetonitrile solution at room temperature. Radical generation was confirmed by nuclear magnetic resonance, electron paramagnetic resonance, ultraviolet-visible-near-infrared spectroscopy and electrospray ionization mass spectrometry. The lifetime of C60• - within the cage was determined to be so large that it could still be detected after one month under an inert atmosphere.

Increasing structural and functional complexity in self-assembled coordination cages.

Progress in metallo-supramolecular chemistry creates potential to synthesize functional nano systems and intelligent materials of increasing complexity. In the past four decades, metal-mediated self-assembly has produced a wide range of structural motifs such as helicates, grids, links, knots, spheres and cages, with particularly the latter ones catching growing attention, owing to their nano-scale cavities. Assemblies serving as hosts allow application as selective receptors, confined reaction environments and more. Recently, the field has made big steps forward by implementing dedicated functionality, e.g. catalytic centres or photoswitches to allow stimuli control. Besides incorporation in homoleptic systems, composed of one type of ligand, desire arose to include more than one function within the same assembly. Inspiration comes from natural enzymes that congregate, for example, a substrate recognition site, an allosteric regulator element and a reaction centre. Combining several functionalities without creating statistical mixtures, however, requires a toolbox of sophisticated assembly strategies. This review showcases the implementation of function into self-assembled cages and devises strategies to selectively form heteroleptic structures. We discuss first examples resulting from a combination of both principles, namely multicomponent multifunctional host–guest complexes, and their potential in application in areas such as sensing, catalysis, and photo-redox systems.

Steric control of sorting regimes in self-assembled cages.

Control of self-sorting regimes is achieved through adjustment of steric interactions in self-assembled coordination cages. The self-assembly regime of dynamic mixtures of heteroleptic cages is followed by HPLC to show that statistical or biased distributions can be selectively obtained, including isolation of a single heteroleptic species.

Hydrolysis of Twisted Amides inside a Self-Assembled Coordination Cage

Mechanical twisting of amides is anticipated to enhance their reactivity considerably. Recent work published in Nature Chemistry by Fujita and co-workers demonstrates that reactive non-planar amide conformers can be bound inside a self-assembled coordination cage. The twisted amides are stabilized by the rigid cavity of the cage and are thus up to 14 times more reactive toward hydrolysis under basic conditions.

Enhanced reactivity of twisted amides inside a molecular cage.

When an amide group is distorted from its planar conformation, the conjugation between the nitrogen lone pair and the π* orbital of the carbonyl is disrupted and the reactivity towards nucleophiles is enhanced. Although there are several reports on the synthesis of activated twisted amides, amide activation through mechanical twisting is much less common. Here, we report twisted amides that are stabilized through their inclusion in a self-assembled coordination cage. When secondary aromatic amides are included in a Td-symmetric cage, the cis-twisted conformation is favoured over the trans-planar one-as evidenced by single-crystal X-ray diffraction analysis-revealing that the amide can twist by up to 34°. As a consequence of this distortion, the hydrolysis of amides is significantly accelerated upon inclusion.

Self-assembled conjoined-cages

A self-assembled coordination cage usually possesses one well-defined three-dimensional (3D) cavity whereas infinite number of 3D-cavities are crafted in a designer metal-organic framework. Construction of a discrete coordination cage possessing multiple number of 3D-cavities is a challenging task. Here we report the peripheral decoration of a trinuclear [Pd3L6] core with one, two and three units of a [Pd2L4] entity for the preparation of multi-3D-cavity conjoined-cages of [Pd4(La)2(Lb)4], [Pd5(Lb)4(Lc)2] and [Pd6(Lc)6] formulations, respectively. Formation of the tetranuclear and pentanuclear complexes is attributed to the favorable integrative self-sorting of the participating components. Cage-fusion reactions and ligand-displacement-induced cage-to-cage transformation reactions are carried out using appropriately chosen ligand components and cages prepared in this work. The smaller [Pd2L4] cavity selectively binds one unit of NO3−, F−, Cl− or Br− while the larger [Pd3L6] cavity accommodates up to four DMSO molecules. Designing aspects of our conjoined-cages possess enough potential to inspire construction of exotic molecular architectures.

Palladium(II)-Based Self-Assembled Heteroleptic Coordination Architectures: A Growing Family.

Metal-driven self-assembly is one of the most effective approaches to lucidly design a large range of discrete 2D and 3D coordination architectures/complexes. Palladium(II)-based self-assembled coordination architectures are usually prepared by using suitable metal components, in either a partially protected form (PdL') or typical form (Pd; charges are not shown), and designed ligand components. The self-assembled molecules prepared by using a metal component and only one type of bi- or polydentate ligand (L) can be classified in the homoleptic series of complexes. On the other hand, the less explored heteroleptic series of complexes are obtained by using a metal component and at least two different types of non-chelating bi- or polydentate ligands (such as La and Lb ). Methods that allow the controlled generation of single, discrete heteroleptic complexes are less understood. A survey of palladium(II)-based self-assembled coordination cages that are heteroleptic has been made. This review article illustrates a systematic collection of such architectures and credible justification of their formation, along with reported functional aspects of the complexes. The collected heteroleptic assemblies are classified here into three sections: 1) [(PdL')m (La )x (Lb )y ]-type complexes, in which the denticity of La and Lb is equal; 2) [(PdL')m (La )x (Lb )y ]-type complexes, in which the denticity of La and Lb is different; and 3) [Pdm (La )x (Lb )y ]-type complexes, in which the denticity of La and Lb is equal. Representative examples of some important homoleptic architectures are also provided, wherever possible, to set a background for a better understanding of the related heteroleptic versions. The purpose of this review is to pave the way for the construction of several unique heteroleptic coordination assemblies that might exhibit emergent supramolecular functions.