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 (L^Qu) and 1,8-naphthyridine (L^Na) donors to generate trans-[Pd₂L₂] and [Pd₂L₃L′] cages, assisted by templation of encapsulated fullerenes. Combined with steric congestion caused by acridine (L^Ac) 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.

Coordination Sphere Engineering (CSE) allows non-statistical assembly of heteroleptic supramolecular architectures by fine adjustment of steric and electronic features around square-planar Pd(ii) cations with naphthyridine donors.     

Topological prediction of palladium coordination cages

The preparation of functionalized, heteroleptic Pd_xL_2x coordination cages is desirable for catalytic and optoelectronic applications. Current rational design of these cages uses the angle between metal-binding (∠B) sites of the di(pyridyl)arene linker to predict the topology of homoleptic cages obtained via non-covalent chemistry. However, this model neglects the contributions of steric bulk between the pyridyl residues—a prerequisite for endohedrally functionalized cages, and fails to rationalize heteroleptic cages. We describe a classical mechanics (CM) approach to predict the topological outcomes of Pd_xL_2x coordination cage formation with arbitrary linker combinations, accounting for the electronic effects of coordination and steric effects of linker structure. Initial validation of our CM method with reported homoleptic Pd₁₂LFu₂₄ (LFu = 2,5-bis(pyridyl)furan) assembly suggested the formation of a minor topology Pd₁₅LFu₃₀, identified experimentally by mass spectrometry. Application to heteroleptic cage systems employing mixtures of LFu (∠B = 127°) and its thiophene congener LTh (∠B = 149° ∠B_exp = 152.4°) enabled prediction of Pd₁₂L₂₄ and Pd₂₄L₄₈ coordination cages formation, reliably emulating experimental data. Finally, the topological outcome for exohedrally (LEx) and endohedrally (LEn) functionalized heteroleptic Pd_xL_2x coordination cages were predicted to assess the effect of steric bulk on both topological outcomes and coordination cage yields, with comparisons drawn to experimental data.

A molecular mechanics approach enables the accurate prediction of polyhedral topology for homoleptic and heteroleptic palladium M_xL_2x coordination cages, allowing for new insight and design when considering endo- and exo-hedral functionalization.     

Morphological Control of Heteroleptic cis- and trans-Pd2L2L′2 Cages

Control over the integrative self-sorting of metallo-supramolecular assemblies opens up possibilities for introducing increased complexity and function into a single self-assembled architecture. Herein, the relationship between the geometry of three ligand components and morphology of three self-sorted heteroleptic [Pd₂ L ₂ L ′₂]⁴⁺ cages is examined. Pd-mediated assembly of two bis-monodentate pyridyl ligands with native bite angles of 75° and 120° affords a cis-[Pd₂ L ₂ L ′₂]⁴⁺ cage while the same reaction with two ligands with bite angles of 75° and 60° gives an unprecedented, self-penetrating structural motif; a trans-[Pd₂(anti- L )₂ L ′₂]⁴⁺ heteroleptic cage with a “doubly bridged figure eight” topology. Each heteroleptic assembly can be formed by cage-to-cage conversion of the homoleptic precursors and morphological control of [Pd₂ L ₂ L ′₂] cages is achieved by selective ligand displacement transformations in a system of three ligands and at least six possible cage products.     

An atropisomeric M2L4 cage mixture displaying guest-induced convergence and strong guest emission in water

Introduction of atropisomeric axes into a bent bispyridine ligand leads to the quantitative formation of a complex mixture of atropisomeric M₂L₄ cages upon treatment with metal ions. Whereas the isomer ratio of the obtained cage mixture, consisting of up to 42 isomers, is insensitive to temperature and solvent, the quantitative convergence from the mixture to a single isomer is accomplished upon encapsulation of a large spherical guest, namely fullerene C₆₀. The observed isomerization with other guests depends largely on their size and shape (e.g., <10 and 82% convergence with planar triphenylene and bowl-shaped corannulene guests, respectively). Besides the unusual guest-induced convergence, the present cage mixture displays the strongest guest emission (Φ_F = 68%) among previously reported M_nL_m cages and capsules, upon encapsulation of a BODIPY dye in water.

A complex mixture of atropisomeric M₂L₄ cages is shown to undergo perfect convergence to a single isomer upon encapsulation of spherical C₆₀ in water. Moreover, the cage mixture displays very strong guest emission upon encapsulation of a BODIPY dye.     

Multi-functional,Low Symmetry Pd2L4 Nanocage Libraries**

Although many impressive metallo-supramolecular architectures have been reported, they tend towards high symmetry structures and avoid extraneous functionality to ensure high fidelity in the self-assembly process. This minimalist approach, however, limits the range of accessible structures and thus their potential applications. Herein is described the synthesis of a family of ditopic ligands wherein the ligand scaffolds are both low symmetry and incorporate exohedral functional moieties. Key to this design is the use of Cu^I-catalysed azide-alkyne cycloaddition (CuAAC) chemistry, as the triazole is capable of acting as both a coordinating heterocycle and a tether between the ligand framework and functional unit simultaneously. A common precursor was used to generate ligands with various functionalities, allowing control of electronic properties whilst maintaining the core structure of the resultant cis-Pd₂L₄ nanocage assemblies. The isostructural nature of the scaffold frameworks enabled formation of combinatorial libraries from the self-assembly of ligand mixtures, generating a statistical mixture of multi-functional, low symmetry architectures.     

Solvent-dependent fac/mer-isomerization and self-assembly of triply helical complexes bearing a pivot part

Tris–chelate metal complexes of unsymmetrical bidentate ligands can form two geometric stereoisomers, facial (fac) and meridional (mer) isomers. Due to the small difference in their properties, the highly-selective synthesis of one of the isomers is challenging. We now designed a series of tripodal ligands with a tris(3-(2-(methyleneoxy)ethoxy)phenyl)methane pivot. Surprisingly, the ratio of the fac/mer isomers of the triply helical Fe^II complexes significantly changed depending on the solvents. To the best of our knowledge, this is the first example of fac/mer isomerism of a labile tris(2,2′-bipyridine) Fe^II complex governed by the solvent. Furthermore, well-defined self-assemblies were quantitatively produced by imine bond formation with a suitable diamine. The supramolecular assemblies contained only the fac isomer even though a mixture of the two isomers existed in solution before the condensation reaction. Namely, the self-assembly formation effectively adjusted the geometries of the building unit that results in the suitable supramolecular structure.

The novel tripodal complexes isomerize in response to environmental change, and well-defined self-assemblies were quantitatively produced by imine bond formation.     

Oxidation triggers guest dissociation during reorganization of an FeII4L6 twisted parallelogram

A three-dimensional Fe^II₄L₆ parallelogram was prepared from ferrocene-containing ditopic ligands. The steric preference of the bulky ferrocene cores towards meridional vertex coordination brought about this new structure type, in which the ferrocene units adopt three distinct conformations. The structure possesses two distinct, bowl-like cavities that host anionic guests. Oxidation of the ferrocene Fe^II to ferrocenium Fe^III causes rotation of the ferrocene hinges, converting the structure to an Fe^II₁L₁⁺ species with release of anionic guests, even though the average charge per iron increases in a way that would ordinarily increase guest binding strength. The degrees of freedom exhibited by these new structures – derived from the different configurations of the three ligands surrounding a meridional Fe^II center and the rotation of ferrocene cores – thus underpin their ability to reconfigure and eject guests upon oxidation.

An oxidation-triggered twist in its ferrocene ligands causes an Fe₄L₆ parallelogram to release its guests and collapse into a high spin Fe₁L₁ structure.     

N2Phos – an easily made,highly effective ligand designed for ppm level Pd-catalyzed Suzuki–Miyaura cross couplings in water

A new biaryl phosphine-containing ligand from an active palladium catalyst for ppm level Suzuki–Miyaura couplings, enabled by an aqueous micellar reaction medium. A wide array of functionalized substrates including aryl/heteroaryl bromides are amenable, as are, notably, chlorides. The catalytic system is both general and highly effective at low palladium loadings (1000–2500 ppm or 0.10–0.25 mol%). Density functional theory calculations suggest that greater steric congestion in N₂Phos induces increased steric crowding around the Pd center, helping to destabilize the 2 : 1 ligand–Pd(0) complex more for N₂Phos than for EvanPhos (and less bulky ligands), and thereby favoring formation of the 1 : 1 ligand–Pd^o complex that is more reactive in oxidative addition to aryl chlorides.

A new, biaryl phosphine-containing ligand, N₂Phos, forms a 1 : 1 complex with Pd resulting in an active catalyst at the ppm level for Suzuki–Miyaura couplings in water, enabled by an aqueous micellar medium. Notably, aryl chlorides are shown to be amenable substrates.     

Tunable Fullerene Affinity of Cages,Bowls and Rings Assembled by PdII Coordination Sphere Engineering

For metal-mediated host compounds, the development of strategies to reduce symmetry and introduce multiple functionalities in a non-statistical way is a challenging task. We show that the introduction of steric stress around the coordination environment of square-planar Pd^II cations and bis-monodentate nitrogen donor ligands allows to control the size and shape of the assembled product, from [Pd₂L₄] cages over [Pd₂L₃] bowl-shaped structures to [Pd₂L₂] rings. Therefore, banana-shaped ligand backbones were equipped with pyridines, two different quinoline isomers and acridine, the latter three introducing steric congestion through hydrogen substituents on annelated benzene rings. Differing behavior of the four resulting hosts towards the binding of C₆₀ and C₇₀ fullerenes was studied and related to structural differences by NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction. The three cages based on pyridine, 6-quinoline or 3-quinoline donors were found to either bind C₆₀, C₇₀ or no fullerene at all.     

Tuning the Size and Geometry of Heteroleptic Coordination Cages by Varying the Ligand Bent Angle

Spherical assemblies of the type [Pd_nL_2n]²ⁿ⁺ can be obtained from Pd^II salts and curved N-donor ligands, L. It is well established that the bent angle, α, of the ligand is a decisive factor in the self-assembly process, with larger angles leading to complexes with a higher nuclearity, n. Herein, we report heteroleptic coordination cages of the type [Pd_nL_nL′_n]²ⁿ⁺, for which a similar correlation between the ligand bent angle and the nuclearity is observed. Tetranuclear cages were obtained by combining [Pd(CH₃CN)₄](BF₄)₂ with 1,3-di(pyridin-3-yl)benzene and ligands featuring a bent angle of α=120°. The use of a dipyridyl ligand with α=149° led to the formation of a hexanuclear complex with a trigonal prismatic geometry; for linear ligands, octanuclear assemblies of the type [Pd₈L₈L′₈]¹⁶⁺ were obtained. The predictable formation of heteroleptic Pd^II cages from 1,3-di(pyridin-3-yl)benzene and different dipyridyl ligands is evidence that there are entire classes of heteroleptic cage structures that are privileged from a thermodynamic point of view.     

A Rotaxane‐like Cage‐in‐Ring Structural Motif for a Metallosupramolecular Pd6L12 Aggregate

A BODIPY‐based bis(3‐pyridyl) ligand undergoes self‐assembly upon coordination to tetravalent palladium(II) cations to form a Pd₆L₁₂ metallosupramolecular assembly with an unprecedented structural motif that resembles a rotaxane‐like cage‐in‐ring arrangement. In this assembly the ligand adopts two different conformations—a C‐shaped one to form a Pd₂L₄ cage which is located in the center of a Pd₄L₈ ring consisting of ligands in a W‐shaped conformation. This assembly is not mechanically interlocked in the sense of catenation but it is stabilized only by attractive π‐stacking between the peripheral BODIPY chromophores and the ligands’ skeleton as well as attractive van der Waals interactions between the long alkoxy chains. As a result, the co‐arrangement of the two components leads to a very efficient space filling. The overall structure can be described as a rotaxane‐like assembly with a metallosupramolecular cage forming the axle in a metallosupramolecular ring. This unique structural motif could be characterized via ESI mass spectrometry, NMR spectroscopy, and X‐ray crystallography.     

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.

This review highlights recent strategies towards the rational synthesis of metallo-supramolecular multicomponent systems, the implementation of functionality and the challenge to create multifunctional assemblies in non-statistical fashion.     

Chiral Self‐Discrimination and Guest Recognition in Helicene‐Based Coordination Cages

Chiral nanosized confinements play a major role for enantioselective recognition and reaction control in biological systems. Supramolecular self‐assembly gives access to artificial mimics with tunable sizes and properties. Herein, a new family of [Pd₂L₄] coordination cages based on a chiral [6]helicene backbone is introduced. A racemic mixture of the bis‐monodentate pyridyl ligand L¹ selectively assembles with Pd^II cations under chiral self‐discrimination to an achiral meso cage, cis‐[Pd₂ L^1P ₂ L^1M ₂]. Enantiopure L¹ forms homochiral cages [Pd₂ L^1P/M ₄]. A longer derivative L² forms chiral cages [Pd₂ L^2P/M ₄] with larger cavities, which bind optical isomers of chiral guests with different affinities. Owing to its distinct chiroptical properties, this cage can distinguish non‐chiral guests of different lengths, as they were found to squeeze or elongate the cavity under modulation of the helical pitch of the helicenes. The CD spectroscopic results were supported by ion mobility mass spectrometry.     

Helix-mediated over 1 nm-range chirality recognition by ligand-to-ligand interactions of dinuclear helicates

Long-range chirality recognition between the two chiral guest ligands can be tuned based on the helix distances (d_Ln–Ln = 11.5 and 14.0 Å) of bis-diketonate bridged dinuclear lanthanide complexes (2Th and 3Th, respectively) used as mediators. Both 2Th and 3Th form one-dimensional (1D) helical structures upon terminal binding of two chiral guest co-ligands (L^R or L^S). Long-range chiral self-recognition is achieved in self-assembly of 2Th with L^R and L^S to preferentially form homochiral assemblies, 2Th-L^R·L^R and 2Th-L^S·L^S, whereas there is no direct molecular interaction between the two guest ligands at the terminal edges. X-ray crystal structure analysis and density functional theory studies reveal that long-range chiral recognition is achieved by terminal ligand-to-ligand interactions between the bis-diketonate ligands and chiral guest co-ligands. Conversely, in self-assembly of 3Th with a longer helix length, statistical binding of L^R and L^S occurs, forming heterochiral (3Th-L^R·L^S) and homochiral (3Th-L^R·L^R and 3Th-L^S·L^S) assemblies in an almost 1 : 1 ratio. When phenyl side arms of the chiral guest co-ligands are replaced by isopropyl groups (L′^R and L′^S), chiral self-recognition is also achieved in the self-assembly process of 3Th with the longer helix length to generate homochiral (3Th-L′^R·L′^R and 3Th-L′^S·L′^S) assemblies as the favored products. Thus, subtle modification of the chiral guests is capable of achieving over 1.4 nm-range chirality recognition.

Long-range chirality recognition between the two chiral guest ligands can be tuned based on the helix distances (d_Ln–Ln = 11.5 and 14.0 Å) of bis-diketonate bridged dinuclear lanthanide complexes (2Th and 3Th, respectively).     

How bulky ligands control the chemoselectivity of Pd-catalyzed N-arylation of ammonia

Steric bulk has been recognized as a central design principle for supporting ligands in the widely utilized Buchwald–Hartwig amination. In a recent example, it was shown that a Pd-catalyst carrying a phosphine ligand can successfully aminate aryl halides using ammonia as the nitrogen source. Interestingly, the chemoselectivity of this reaction was found to depend on the steric demand of the phosphine ligand. Whereas a sterically less demanding phosphine affords diphenylamine as the major product, it was shown that the amination reaction can be stopped after the first amination to give aniline if a sterically more encumbering phosphine ligand is used. Density functional theory calculations were carried out to examine the relationship between the steric demand of the phosphine ligand and the chemoselectivity. It was found that the key feature that leads to the chemoselectivity is the ability of the phosphine ligand to rotate the biaryl moiety of the ligand away from the Pd-center upon amine addition to release some of the steric crowding from the Pd-coordination site.

Steric bulk has been recognized as a central design principle for ligands in the widely utilized Buchwald–Hartwig amination. This mechanistic study reveals how this steric effect manipulates the reaction pathway and determines the chemoselectivity.     

Dynamic Open Coordination Cage from Nonsymmetrical Imidazole–Pyridine Ditopic Ligands for Turn‐On/Off Anion Binding

This work demonstrates a new nonconventional ligand design, imidazole/pyridine‐based nonsymmetrical ditopic ligands ( 1 and 1 ^S ), to construct a dynamic open coordination cage from nonsymmetrical building blocks. Upon complex formation with Pd²⁺ at a 1:4 molar ratio, 1 and 1 ^S initially form mononuclear PdL₄ complexes (Pd²⁺( 1 )₄ and Pd²⁺( 1 ^S )₄) without formation of a cage. The PdL₄ complexes undergo a stoichiometrically controlled structural transition to Pd₂L₄ open cages ((Pd²⁺)₂( 1 )₄ and (Pd²⁺)₂( 1 ^S )₄) capable of anion binding, leading to turn‐on anion binding. The structural transitions between the Pd₂L₄ open cage and the PdL₄ complex are reversible. Thus, stoichiometric addition (2 equiv) of free 1 ^S to the (Pd²⁺)₂( 1 ^S )₄ open cage holding a guest anion ((Pd²⁺)₂( 1 ^S )₄?G^?) enables the structural transition to the Pd²⁺( 1 ^S )₄ complex, which does not have a cage and thus causes the release of the guest anion (Pd²⁺( 1 ^S )₄+G^?).     

“Bottled” spiro-doubly aromatic trinuclear [Pd2Ru]+ complexes

Following an ongoing interest in the study of transition metal complexes with exotic bonding networks, we report herein the synthesis of a family of heterobimetallic triangular clusters involving Ru and Pd atoms. These are the first examples of trinuclear complexes combining these nuclei. Structural and bonding analyses revealed both analogies and unexpected differences for these [Pd₂Ru]⁺ complexes compared to their parent [Pd₃]⁺ peers. Noticeably, participation of the Ru atom in the π-aromaticity of the coordinated benzene ring makes the synthesized compound the second reported example of ‘bottled’ double aromaticity. This can also be referred to as spiroaromaticity due to the participation of Ru in two aromatic systems at a time. Moreover, the [Pd₂Ru]⁺ kernel exhibits unprecedented orbital overlap of Ru d_z² AO and two Pd d_xy or d_x²−y² AOs. The present findings reveal the possibility of synthesizing stable clusters with delocalized metal–metal bonding from the combination of non-adjacent elements of the periodic table which has not been reported previously.

Synthesis of a triangular [Pd₂Ru]⁺ complex with delocalized metal–metal bonding between non-adjacent elements of the periodic table, double aromaticity and overlap of d-AOs with different angular momentum.     

Engineering Soluble Diketopyrrolopyrrole Chromophore Stacks from a Series of Pd(II)-Based Ravels**

A strategy to engineer the stacking of diketopyrrolopyrrole (DPP) dyes based on non-statistical metallosupramolecular self-assembly is introduced. For this, the DPP backbone is equipped with nitrogen-based donors that allow for different discrete assemblies to be formed upon the addition of Pd(II), distinguished by the number of π-stacked chromophores. A Pd₃L₆ three-ring, a heteroleptic Pd₂L₂L′₂ ravel composed of two crossing DPPs (flanked by two carbazoles), and two unprecedented self-penetrated motifs (a Pd₂L₃ triple and a Pd₂L₄ quadruple stack), were obtained and systematically investigated. With increasing counts of stacked chromophores, UV/Vis absorptions red-shift and emission intensities decrease, except for compound Pd₂L₂L′₂, which stands out with an exceptional photoluminescence quantum yield of 51 %. This is extraordinary for open-shell metal containing assemblies and explainable by an intra-assembly FRET process. The modular design and synthesis of soluble multi-chromophore building blocks offers the potential for the preparation of nanodevices and materials with applications in sensing, photo-redox catalysis and optics.     

Synthesis of side-chain regioregular and main-chain alternating poly(bichalcogenophene)s and an ABC-type periodic poly(terchalcogenophene)

Three unsymmetrical diiodobichalcogenophenes SSeI2, STeI2, and SeTeI2 and a diiodoterchalcogenophene SSeTeI2 were prepared. Grignard metathesis of SSeI2, STeI2, SeTeI2, and SSeTeI2 occurred regioselectively at the lighter chalcogenophene site because of its relatively lower electron density and less steric bulk. Nickel-catalyzed Kumada catalyst-transfer polycondensation of these Mg species provided a new class of side-chain regioregular and main-chain AB-type alternating poly(bichalcogenophene)s—PSSe, PSTe, and PSeTe—through a chain-growth mechanism. The ring-walking of the Ni catalyst from the lighter to the heavier chalcogenophene facilitated subsequent oxidative addition, thereby suppressing the possibility of chain-transfer or chain-termination. More significantly, the Ni catalyst could walk over the distance of three rings (ca. 1 nm)—from a thiophene unit via a selenophene unit to a tellurophene unit—to form PSSeTe, the first ABC-type regioregular and periodic poly(terchalcogenophene) comprising three different types of 3-hexylchalcogenophenes.

Three unsymmetrical diiodobichalcogenophenes SSeI2, STeI2, and SeTeI2 and a diiodoterchalcogenophene SSeTeI2 were prepared to synthesize a new class of polychalcogenophenes with precisely controlled sequences by catalyst-transfer polycondensation.