Metallosupramolecular Architectures Research Articles

In vitro anticancer activity of a head-to-toe constructed heterobimetallic [CoFeL]2+ metallocylinder

ABSTRACT [M2L3]-type metallo-supramolecular architectures (MSAs) are widely explored for their biological activity, whereas data on non-symmetric, heterobimetallic [MM’L3] structures is comparatively rare. [M2L3] compounds are known to form helicates and/or mesocates. Here, we report the self-assembly of a discrete non-symmetrical, heterobimetallic MSA by combination of an amine-functionalised cobalt(III)-tris((picolinamido)ethyl)amine (PICTREN) base unit with FeCl2 and 2,2’-bipyridine-5-carboxaldehyde. NMR spectroscopy in tandem with computational studies revealed the formation of a mesocate rather than a helicate. The ability of the heteromesocate to bind to DNA was examined by gel electrophoresis with pUC19 plasmid DNA, which showed DNA binding although longer incubation periods were required than found for a known DNA-interacting helicate. The mesocate displayed promising antiproliferative activity in cancer cells, including a cisplatin-resistant cell line, with IC50 values in the 17–26 μM range. Lower biological activity of the mesocate compared to a metallocylinder reference and cisplatin may be explained by differences in the DNA interactions. This work further supports efforts to establish methods with which to construct heterobimetallic complexes, establishing the utility of the self-assembly method in [M2L3]-type assemblies using the cobalt(III)-PICTREN platform as a robust building block towards more complex assemblies of the [MM’L]-type.

Pt(II)/Pd(II)-Based Metallosupramolecular Architectures as Light Harvesting Systems and their Applications.

The development of artificial light-harvesting systems mimicking the natural photosynthesis method is an ever-growing field of research. Numerous systems such as polymers, metal complexes, POFs, COFs, supramolecular frameworks etc. have been fabricated to accomplish more efficient energy transfer and storage. Among them, the supramolecular coordination complexes (SCCs) formed by non-covalent metal-ligand interaction, have shown the capacity to not only undergo single and multistep energy migration but also to utilize the harvested energy for a wide variety of applications such as photocatalysis, tunable emissive systems, encrypted anti-counterfeiting materials, white light emitters etc. This review sheds light on the light-harvesting behavior of both the 2D metallacycles and 3D metallacages where design ingenuity has been executed to afford energy harvesting by both donor ligands as well as metal acceptors.

Pt(II)/Pd(II)‐Based Metallosupramolecular Architectures as Light Harvesting Systems and their Applications

AbstractThe development of artificial light‐harvesting systems mimicking the natural photosynthesis method is an ever‐growing field of research. Numerous systems such as polymers, metal complexes, POFs, COFs, supramolecular frameworks etc. have been fabricated to accomplish more efficient energy transfer and storage. Among them, the supramolecular coordination complexes (SCCs) formed by non‐covalent metal‐ligand interaction, have shown the capacity to not only undergo single and multistep energy migration but also to utilize the harvested energy for a wide variety of applications such as photocatalysis, tunable emissive systems, encrypted anti‐counterfeiting materials, white light emitters etc. This review sheds light on the light‐harvesting behavior of both the 2D metallacycles and 3D metallacages where design ingenuity has been executed to afford energy harvesting by both donor ligands as well as metal acceptors.

Heterometallic cages: synthesis and applications.

High symmetry metallosupramolecular architectures (MSAs) have been exploited for a range of applications including molecular recognition, catalysis and drug delivery. Recently there have been increasing efforts to enhance those applications by generating reduced symmetry MSAs. While there are several emerging methods for generating lower symmetry MSAs, this tutorial review examines the general methods used for synthesizing heterometallic MSAs with a particular focus on heterometallic cages. Additionally, the intrinsic properties of the cages and their potential emerging applications as host-guest systems and reaction catalysts are described.

Towards building blocks for metallosupramolecular structures: non-symmetrically-functionalised ferrocenyl compounds.

Metallosupramolecular architectures formed from metal ions and bridging ligands are increasing in popularity due to their range of applications and ease of self-assembly. Many are able to readily change their shape and/or function in response to an external stimulus and have the ability to encapsulate guest molecules within their internal cavities. Ferrocenyl groups (Fc) have been incorporated previously within the bridging ligands of metallosupramolecular structures due to their ideal attributes brought about by the structural and rotational flexiblity of the two cyclopentadienyl (Cp) rings coordinated to the Fe(II) centre. However, the majority of these Fc-based structures contain symmetrically substituted Cp rings. We report the synthesis and characterisation of non-symmetrically functionalised Fc-based ligands incorporating both N,N' and NHC-donor groups chosen for their differing coordination properties. Both substituents were designed to coordinate to a single metal centre with the dissimilar coordination properties of each donor group facilitating stimulus-induced dissociation/association of one of the substituents as an opening/closing mechanism. Preliminary investigations into the coordination of these Fc-based ligands to a [Ru(η6-p-cymene)]2+ moiety indicated complexation through a mixture of either a bi- or tridentate fashion, as alluded by 1H NMR spectroscopy and mass spectrometry. Density functional theory (DFT) calculations revealed the Fc-based ligands adopt a syn conformation driven by H-bonding and π-interactions between the two Cp substituents, which facilitate coordination of both donor groups towards the metal centre.

Mononuclear or Coordination Polymer Complexes? Both Are Possible for 3,6,9-Trioxaundecanedioic Acid

Investigating the driving forces leading to the formation of a specific supramolecular architecture among a wide spectrum of all the possibly obtainable structures is not an easy task. The contemporary literature provides several models for correctly predicting the thermodynamically accessible structures that can originate from a library of building blocks. Definitions are rigid by their very nature, so their application may sometimes require a shift in perspective. In the study presented herein, we describe the crystal structures of three metallo-supramolecular architectures assembled from deprotonated derivatives of 3,6,9-trioxaundecanedioic acid and Mn(II), Co(II) and Zn(II). In the Mn(II) case, the complexation resulted in a complex of a discrete/heptacoordinated nature, whereas the other two structures appeared as helical polymers. To explain such an anomaly, in this work, we describe how the interplay between the flexibility of the ligand spacer and the number of coordinating atoms involved determines the divergent or convergent organisation of the final coordination architecture.

Unexpected structural complexity of d-block metallosupramolecular architectures within the benzimidazole-phenoxo ligand scaffold for crystal engineering aspects

Design of metallosupramolecular materials encompassing more than one kind of supramolecular interaction can become deceptive, but it is necessary to better understand the concept of the controlled formation of supramolecular systems. Herein, we show the structural diversity of the bis-compartmental phenoxo-benzimidazole ligand H3L1 upon self-assembly with variety of d-block metal ions, accounting for factors such as: counterions, pH, solvent and reaction conditions. Solid-state and solution studies show that the parent ligand can accommodate different forms, related to (de)protonation and proton-transfer, resulting in the formation of mono-, bi- or tetrametallic architectures, which was also confirmed with control studies on the new mono-compartmental phenoxo-benzimidazole H2L2 ligand analogue. For the chosen architectures, structural variables such as porous character, magnetic behaviour or luminescence studies were studied to demonstrate how the form of H3L1 ligand affects the final form of the supramolecular architecture and observed properties. Such complex structural variations within the benzimidazole-phenoxo-type ligand have been demonstrated for the first time and this proof-of-concept can be used to integrate these principles in more sophisticated architectures in the future, combining both the benzimidazole and phenoxide subunits. Ultimately, those principles could be utilized for targeted manipulation of properties through molecular tectonics and crystal engineering aspects.

Post-coordination photoinitiated macromolecular thiol-ene coupling reaction for construction of metallo-supramolecular complexes of ABCL2-type miktoarm star copolymers and self-assembly of the complexes in water

In this paper, we focus on investigating synthesis of metallo-supramolecular architectures of ABCL2-type miktoarm star copolymers PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] (A, PCL; B, PDPA; C, PMPC; L, Tpyp) with ruthenium(II) (Ru(II)) ions and exploring self-assembly behavior of the complexes in water. Direct coordination of PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] to Ru(II) ions and post-coordination photoinitiated macromolecular thiol-ene coupling reaction strategies were explored to construct Ru(II) coordination complexes, respectively. The result indicates that the post-coordination coupling reaction was more suitable strategy for constructing this kind of coordination complexes, which may avoid a larger steric hindrance generated from the coexistence of the three arms of PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] leading to the disadvantageous influence on the formation of the bis(terpyridine)-Ru(II) complex. It should be mentioned that, however, although a photoinitiated macromolecular thiol-ene radical coupling reaction is facile, so far to achieve complete reaction of the target groups (i.e., alkene groups) has remained a challenge. Therefore, herein a post-coordination thiol-ene coupling reaction was explored carefully and an appropriate condition for the complete reaction of the alkene groups was given. Interestingly, the Ru(II) coordination complexes could self-assemble to form 2D platelets. This should be attributed to the unique metallo-supramolecular architecture. It is expected that the exploration can provide strategies for construction of complicated and exquisite metallo-supramolecular architectures and novel self-assemblies.

Schiff Bases Functionalized with T-Butyl Groups as Adequate Ligands to Extended Assembly of Cu(II) Helicates.

The study of the inherent factors that influence the isolation of one type of metallosupramolecular architecture over another is one of the main objectives in the field of Metallosupramolecular Chemistry. In this work, we report two new neutral copper(II) helicates, [Cu2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN, obtained by means of an electrochemical methodology and derived from two Schiff-based strands functionalized with ortho and para-t-butyl groups on the aromatic surface. These small modifications let us explore the relationship between the ligand design and the structure of the extended metallosupramolecular architecture. The magnetic properties of the Cu(II) helicates were explored by Electron Paramagnetic Resonance (EPR) spectroscopy and Direct Current (DC) magnetic susceptibility measurements.

Frontispiece: The Biologically Inspired Abilities of Metallosupramolecular Architectures

This article highlights recent efforts to mimic biological systems and functions using metallosupramolecular architectures. Read more in the Review by A. C. Pearcy and J. D. Crowley (10.1002/chem.202203752).

The Biologically Inspired Abilities of Metallosupramolecular Architectures.

Natural machinery such as proteins and enzymes can bind substrates and perform intricate functions on these molecules. This behaviour is mediated by highly ordered but conformationally flexible structures dictated through favourable intra- and intermolecular interactions. Metallosupramolecular architectures (MSAs) function as synthetic machinery that are responsive to their environment, and display similar, but less impressive, abilities to their biological counterparts. Natural and synthetic systems share the properties of molecular recognition and catalysis facilitated through the often complex structures of these architectures. This article outlines efforts to use metallosupramolecular structures to mimic the properties of biological enzymes and machines using important recent examples from the field.

Investigating the Conformations of a Family of [M2L3]4+ Helicates Using Single Crystal X-ray Diffraction.

We present five new dinuclear triple helicate compounds of types [Mn2L3](ClO4)4, [Co2L3](BF4)4, [Ni2L3](BF4)4, [Cu2L3](BF4)4, and [Zn2L3](BF4)4, where L is a previously reported semi-rigid ligand incorporating two α-diimine primary donor groups and two secondary 4-pyridyl donor groups. All complexes have been characterized in both solution and the solid state. Single crystal X-ray diffraction studies were used to probe the variation in the respective helical structures as the coordinated metal ion was altered, including the effect on the orientations of the secondary binding domains. The influence of the metal ion size, the spin state in the case of Fe(II), and the presence of Jahn-Teller distortions on the overall helical structure has been investigated. These results form a basis for the design and construction of new large metallosupramolecular architectures which manifest properties associated with the constituent helical metalloligand units.

PET Imaging of Self-Assembled 18 F-Labelled Pd2 L4 Metallacages for Anticancer Drug Delivery.

To advance the design of self-assembled metallosupramolecular architectures as new generation theranostic agents, the synthesis of 18 F-labelled [Pd2 L4 ]4+ metallacages is reported. Different spectroscopic and bio-analytical methods support the formation of the host-guest cage-cisplatin complex. The biodistribution profiles of one of the cages, alone or encapsulating cisplatin have been studied by PET/CT imaging in healthy mice in vivo, in combination to ICP-MS ex vivo.

Crystallization- and Metal-Driven Selection of Discrete Macrocycles/Cages and Their Metallosupramolecular Polymers from Dynamic Systemic Networks

Reversible imine- and metal-coordination reactions are dynamic enough to produce complex libraries of macrocycles, cages, and supramolecular polymers in solution, from which amplification effects have been identified in solution or during crystallization in response to ligand- and metal-driven selection modes. Crystallization-driven selection can lead to the amplification of unexpected metallosupramolecular architectures. The addition of Ag+ triggered the change of the optimal components, so that the crystallization process showed different ligand preferences than in solution. The most packed constituents are amplified in the solid state, taking into account the optimal coordination of metal ions together with non-specific non-covalent interactions between the macrocycle packed in dimers or trimers in the solid state.

Two Synthetic Approaches to Coinage Metal(I) Mesocates: Electrochemical versus Chemical Synthesis.

We report two different approaches to isolate neutral and cationic mesocate-type metallosupramolecular architectures derived from coinage monovalent ions. For this purpose, we use a thiocarbohydrazone ligand, H2L (1), conveniently tuned with bulky phosphine groups to stabilize the MI ions and prevent ligand crossing to achieve the selective formation of mesocates. The neutral complexes [Cu2(HL)2] (2), [Ag2(HL)2] (3), and [Au2(HL)2] (4) were prepared by an electrochemical method, while the cationic complexes [Cu2(H2L)2](PF6)2 (5), [Cu2(H2L)2](BF4)2 (6), [Ag2(H2L)2](PF6)2 (7), [Ag4(HL)2](NO3)2 (8), and [Au2(H2L)2]Cl2 (9) were obtained by using a metal salt as the precursor. All of the complexes are neutral or cationic dinuclear mesocates, except the silver nitrate derivative, which exhibits a tetranuclear cluster mesocate architecture. The crystal structures of the neutral and cationic copper(I), silver(I), and gold(I) complexes allow us to analyze the influence of synthetic methodology or the counterion role on both the micro- and macrostructures of the mesocates.

Circularly Polarized Luminescence Active Supramolecular Nanotubes Based on PtII Complexes That Undergo Dynamic Morphological Transformation and Helicity Inversion

AbstractCircularly polarized luminescence (CPL) with tunable chirality is currently a challenging issue in the development of supramolecular nanomaterials. We herein report the formation of helical nanoribbons which grow into helical tubes through dynamic helicity inversion. For this, chiral PtII complexes of terpyridine derivatives, namely S‐trans‐1 and R‐trans‐1, with respective S‐ and R‐alanine subunits and incorporating trans‐double bonds in the alkyl chain were prepared. In DMSO/H2O (5 : 1 v/v), S‐trans‐1 initially forms a fibrous self‐assembled product, which then undergoes dynamic transformation into helical tubes (left‐handed or M‐type) through helical ribbons (right‐handed or P‐type). Interestingly, both helical supramolecular architectures are capable of emitting CPL signals. The metastable helical ribbons show CPL signals (glum=±4.7×10−2) at 570 nm. Meanwhile, the nanotubes, which are the thermodynamic products, show intense CPL signals (glum=±5.6×10−2) at 610 nm accompanied by helicity inversion. This study provides an efficient way to develop highly dissymmetric CPL nanomaterials by regulating the morphology of metallosupramolecular architectures.

Circularly Polarized Luminescence Active Supramolecular Nanotubes Based on PtII Complexes That Undergo Dynamic Morphological Transformation and Helicity Inversion.

Circularly polarized luminescence (CPL) with tunable chirality is currently a challenging issue in the development of supramolecular nanomaterials. We herein report the formation of helical nanoribbons which grow into helical tubes through dynamic helicity inversion. For this, chiral PtII complexes of terpyridine derivatives, namely S-trans-1 and R-trans-1, with respective S- and R-alanine subunits and incorporating trans-double bonds in the alkyl chain were prepared. In DMSO/H2 O (5 : 1 v/v), S-trans-1 initially forms a fibrous self-assembled product, which then undergoes dynamic transformation into helical tubes (left-handed or M-type) through helical ribbons (right-handed or P-type). Interestingly, both helical supramolecular architectures are capable of emitting CPL signals. The metastable helical ribbons show CPL signals (glum =±4.7×10-2 ) at 570 nm. Meanwhile, the nanotubes, which are the thermodynamic products, show intense CPL signals (glum =±5.6×10-2 ) at 610 nm accompanied by helicity inversion. This study provides an efficient way to develop highly dissymmetric CPL nanomaterials by regulating the morphology of metallosupramolecular architectures.

Exploiting Supramolecular Interactions to Control Isomer Distributions in Reduced-Symmetry [Pd2L4]4+ Cages.

High-symmetry metallosupramolecular architectures (MSAs) have been exploited for a range of applications including molecular recognition, catalysis, and drug delivery. Recently, there have been increasing efforts to enhance those applications by generating reduced-symmetry MSAs. Here we report our attempts to use supramolecular (dispersion and hydrogen-bonding) forces and solvophobic effects to generate isomerically pure [Pd2(L)4]4+ cage architectures from a family of new reduced-symmetry ditopic tripyridyl ligands. The reduced-symmetry tripyridyl ligands featured either solvophilic polyether chains, solvophobic alkyl chains, or amino substituents. We show using NMR spectroscopy, high-performance liquid chromatography, X-ray diffraction data, and density functional theory calculations that the combination of dispersion forces and solvophobic effects does not provide any control of the [Pd2(L)4]4+ isomer distribution with mixtures of all four cage isomers (HHHH, HHHT, cis-HHTT, or trans-HTHT, where H = head and T = tail) obtained in each case. More control was obtained by exploiting hydrogen-bonding interactions between amino units. While the cage assembly with a 3-amino-substituted tripyridyl ligand leads to a mixture of all four possible isomers, the related 2-amino-substituted tripyridyl ligand generated a cis-HHTT cage architecture. Formation of the cis-HHTT [Pd2(L)4]4+ cage was confirmed using NMR studies and X-ray crystallography.

Terpyridine-Based 3D Discrete Metallosupramolecular Architectures.

Terpyridine (tpy)-based 3D discrete metallosupramolecular architectures, which are often inspired by polyhedral geometry and the biological structures found in nature, have drawn significant attention from the community of metallosupramolecular chemistry. Because of the linear tpy-M(II)-tpy connectivity, the creation of sophisticated 3D metallosupramolecules based on tpy remains a formidable synthetic challenge. Nevertheless, with recent advancement in ligand design and self-assembly, diverse 3D metallosupramolecular polyhedrons, such as Platonic solids, Archimedean solids, prims as well as Johnson solids, have been constructed and their potential applications have been explored. This review summarizes the progress on tpy-based discrete 3D metallosupramolecules, aiming to shed more light on the design and construction of novel discrete architectures with molecular-level precision through coordination-driven self-assembly.

Cooperativity of steric bulk and H-bonding in coordination sphere engineering: heteroleptic PdII cages and bowls by design.

Recently developed self-assembly strategies allow to rationally reduce the symmetry of metallosupramolecular architectures. In addition, the combination of multiple ligand types without creating compound mixtures has become possible. Among several approaches to realize non-statistical heteroleptic assembly, Coordination Sphere Engineering (CSE) makes use of secondary repulsive or attractive interactions in direct vicinity of the metal nodes. Previously, we used steric congestion to turn dinuclear [Pd2L4] cages with fourfold symmetry into [Pd2L3X2] (X = solvent, halide) bowl structures. Here, we introduce a new subtype of this strategy based on balancing hydrogen bonding and repulsive interactions between ligands carrying quinoline (LQu) and 1,8-naphthyridine (LNa) donors to generate trans-[Pd2L2] and [Pd2L3L′] cages, assisted by templation of encapsulated fullerenes. Combined with steric congestion caused by acridine (LAc) donors, we further report the first example of a heteroleptic [Pd2L2L′X2] bowl. Formation, structure and fullerene binding ability of these metallo-supramolecular hosts were studied by NMR, mass spectrometry and single crystal X-ray diffraction.