Metallosupramolecular cages: from design principles and characterisation techniques to applications.

Although metallosupramolecular cages are self-assembled from seemingly simple building blocks, metal ions and organic ligands, architectures of increasingly large size and complexity are accessible and exploited in applications from catalysis to the stabilisation of reactive species. This Tutorial Review gives an introduction to the principles for designing metallosupramolecular cages and highlights advances in the design of large and lower symmetry cages. The characterisation and identification of cages relies on a number of complementary techniques with NMR spectroscopy, mass spectrometry, X-ray crystallography and computational methods being the focus of this review. Finally, examples of cages are discussed where these design principles and characterisation techniques are put into practice for an application or function of the cage.

Light-Controlled Destruction and Assembly: Switching between Two Differently Composed Cage-Type Complexes.

We report on two regioisomeric, diazocine ligands 1 and 2 that can both be photoswitched between the E- and Z-configurations with violet and green light. The self-assembly of the four species (1-Z, 1-E, 2-Z, 2-E) with CoII ions was investigated upon changing the coordination vectors as a function of the ligand configuration (E vs Z) and regioisomer (1 vs 2). With 1-Z, Co2 (1-Z)3 was self-assembled, while a mixture of ill-defined species (oligomers) was observed with 2-Z. Upon photoswitching with 385 nm to the E configurations, the opposite was observed with 1-E forming oligomers and 2-E forming Co2 (2-E)3 . Light-controlled dis/assembly was demonstrated in a ligand competition experiment with sub-stoichiometric amounts of CoII ions; alternating irradiation with violet and green light resulted in the reversible transformation between Co2 (1-Z)3 and Co2 (2-E)3 over multiple cycles without significant fatigue by photoswitching.

An Area-Specific, International Community-Led Approach to Understanding and Addressing Equality, Diversity, and Inclusion Issues within Supramolecular Chemistry.

Diversity, equality, and inclusion (DEI/EDI) are pressing issues in chemistry and the natural sciences. In this Essay we share how an area-specific approach is "calling in" the community so that it can act to address EDI issues, and support those who are marginalised. Women In Supramolecular Chemistry (WISC) is an international network that aims to support equality, diversity, and inclusion within supramolecular chemistry. WISC has taken a field-specific approach using qualitative research methods with scientists to identify the support that is needed and the problems the supramolecular community needs to address. Herein, we present survey data from the community which highlight the barriers that are faced by those who take career breaks for any reason, a common example is maternity leave, and the importance of mentoring to aid progression post-PhD. In conclusion, we set out an interdisciplinary and creative approach to addressing EDI issues within supramolecular chemistry.

A Paramagnetic NMR Spectroscopy Toolbox for the Characterisation of Paramagnetic/Spin-Crossover Coordination Complexes and Metal-Organic Cages.

The large paramagnetic shifts and short relaxation times resulting from the presence of a paramagnetic centre complicate NMR data acquisition and interpretation in solution. As a result, NMR analysis of paramagnetic complexes is limited in comparison to diamagnetic compounds and often relies on theoretical models. We report a toolbox of 1D (1H, proton-coupled 13C, selective 1H-decoupling 13C, steady-state NOE) and 2D (COSY, NOESY, HMQC) paramagnetic NMR methods that enables unprecedented structural characterisation and in some cases, provides more structural information than would be observable for a diamagnetic analogue. We demonstrate the toolbox's broad versatility for fields from coordination chemistry and spin-crossover complexes to supramolecular chemistry through the characterisation of CoII and high-spin FeII mononuclear complexes as well as a Co4L6 cage.

Orthogonal Stimuli Trigger Self-Assembly and Phase Transfer of FeII4L4 Cages and Cargoes.

Two differently protected aldehydes, A and B, were demonstrated to deprotect selectively through the application of light and heat, respectively. In the presence of iron(II) and a triamine, two distinct FeII4L4 cages, 1 and 2, were thus observed to form from the deprotected A and B, respectively. The alkyl tails of B and 2 render them preferentially soluble in cyclopentane, whereas A and 1 remain in acetonitrile. The stimulus applied (either light or heat) thus determines the outcome of self-assembly and dictates whether the cage and its ferrocene cargo remain in acetonitrile, or transport into cyclopentane. Cage self-assembly and cargo transport between phases can in this fashion be programmed using orthogonal stimuli.

Post-Assembly Reactivity of N-Aryl Iminoboronates: Reversible Radical Coupling and Unusual B-N Dynamic Covalent Chemistry.

Post-assembly reaction of a dynamic covalent iminoboronate system following addition of Cp2 Co resulted in the formation of a series of new reductively coupled dianionic dimers via C-C bond formation. The dimers formed as a mixture of BN-containing isomeric products: diastereomers rac5 and meso5, with coupled five-membered rings, and enantiomeric rac6, with a fused six-membered ring bicyclic system from C-C bond formation and rearrangement of the B-N bonds. Each isomer was identified using 1 H NMR spectroscopy in combination with single crystal X-ray structure determination. Interestingly, interconversion between the coupled five-membered rings (rac5 ) and fused bicyclic systems (rac6 ) was found to occur through an unprecedented breaking and reforming of the B-N covalent bond. Further, the coupled products could be converted quantitatively back to their iminoboronate precursors with addition of the electron abstractor Ph3 C+ .

Subcomponent Exchange Transforms an FeII4L4 Cage from High- to Low-Spin, Switching Guest Release in a Two-Cage System.

Subcomponent exchange transformed new high-spin FeII4L4 cage 1 into previously-reported low-spin FeII4L4 cage 2: 2-formyl-6-methylpyridine was ejected in favor of the less sterically hindered 2-formylpyridine, with concomitant high- to low-spin transition of the cage's FeII centers. High-spin 1 also reacted more readily with electron-rich anilines than 2, enabling the design of a system consisting of two cages that could release their guests in response to combinations of different stimuli. The addition of p-anisidine to a mixture of high-spin 1 and previously-reported low-spin FeII4L6 cage 3 resulted in the destruction of 1 and the release of its guest. However, initial addition of 2-formylpyridine to an identical mixture of 1 and 3 resulted in the transformation of 1 into 2; added p-anisidine then reacted preferentially with 3 releasing its guest. The addition of 2-formylpyridine thus modulated the system's behavior, fundamentally altering its response to the subsequent signal p-anisidine.

A Ruthenium(II) Complex as a Luminescent Probe for DNA Mismatches and Abasic Sites.

[Ru(bpy)2(BNIQ)]2+ (BNIQ = Benzo[c][1,7]naphthyridine-1-isoquinoline), which incorporates the sterically expansive BNIQ ligand, is a highly selective luminescent probe for DNA mismatches and abasic sites, possessing a 500-fold higher binding affinity toward these destabilized regions relative to well-matched base pairs. As a result of this higher binding affinity, the complex exhibits an enhanced steady-state emission in the presence of DNA duplexes containing a single base mismatch or abasic site compared to fully well-matched DNA. Luminescence quenching experiments with Cu(phen)22+ and [Fe(CN)6]3- implicate binding of the complex to a mismatch from the minor groove via metalloinsertion. The emission response of the complex to different single base mismatches, binding preferentially to the more destabilized mismatches, is also consistent with binding by metalloinsertion. This work shows that high selectivity toward destabilized regions in duplex DNA can be achieved through the rational design of a complex with a sterically expansive aromatic ligand.

Luminescence of [Ru(bpy)2(dppz)]2+ bound to RNA mismatches.

The luminescence of rac-[Ru(bpy)2(dppz)](2+) (bpy = 2,2'-bipyridine and dppz = dipyrido[3,2-a:2',3'-c]phenazine) was explored in the presence of RNA oligonucleotides containing a single RNA mismatch (CA and GG) in order to develop a probe for RNA mismatches. While there is minimal luminescence of [Ru(bpy)2(dppz)](2+) in the presence of matched RNA due to weak binding, the luminescence is significantly enhanced in the presence of a single CA mismatch. The luminescence differential between CA mismatched and matched RNA is substantially higher compared to the DNA analogue, and therefore, [Ru(bpy)2(dppz)](2+) appears to be also a sensitive light switch probe for a CA mismatch in duplex RNA. Although the luminescence intensity is lower in the presence of RNA than DNA, Förster resonance energy transfer (FRET) between the donor ruthenium complex and FRET acceptor SYTO 61 is successfully exploited to amplify the luminescence in the presence of the mismatch. Luminescence and quenching studies with sodium iodide suggest that [Ru(bpy)2(dppz)](2+) binds to these mismatches via metalloinsertion from the minor groove. This work provides further evidence that metalloinsertion is a general binding mode of octahedral metal complexes to thermodynamically destabilized mismatches not only in DNA but also in RNA.

Amidoboronates: bringing together the synthesis of BN-heterocycles via a reductive coupling and dynamic covalent chemistry.

This Perspective describes how amidoboronates open up new chemical space spanning the areas of BN-heterocycles and dynamic covalent chemistry. BN-containing heterocycles offer the potential to access new properties and reactivity compared to their C-C analogues. Amidoboronates are introduced as a new class of B-N heterocycles that can be synthesised in three isomeric forms (meso5, rac5 and rac6) from the reductive coupling of N-aryl iminoboronates. Furthermore, initial investigations on the dynamic covalent chemistry of amidoboronates are discussed, such as the reversibility of C-C bond formation following the reductive coupling and tuning the rac5/rac6 ratio via dynamic covalent B-N and B-O bonds.

Tuning the spin-crossover properties of FeII4L6 cages via the interplay of coordination motif and linker modifications.

Despite the increasing number of spin-crossover FeII-based cages, the interplay between ligand modifications (e.g. coordination motif substituents and linker) is not well-understood in these multinuclear systems, limiting rational design. Here, we report a family of FeII4L6 spin-crossover cages based on 2,2'-pyridylbenzimidazoles where subtle ligand modifications lowered the spin crossover temperature in CD3CN by up to 186 K. Comparing pairs of cages, CH3 substituents on either the coordination motif or phenylene linker lowered the spin-crossover temperature by 48 K, 91 K or 186 K, attributed to electronic effects, steric effects and a combination of both, respectively. The understanding of the interplay between ligand modifications gained from this study could be harnessed on the path towards the improved rational design of spin-crossover cages.

Luminescent properties of ruthenium(II) complexes with sterically expansive ligands bound to DNA defects.

A new family of ruthenium(II) complexes with sterically expansive ligands for targeting DNA defects was prepared, and their luminescent responses to base pair mismatches and/or abasic sites were investigated. Design of the complexes sought to combine the mismatch specificity of sterically expansive metalloinsertors, such as [Rh(bpy)2(chrysi)](3+) (chrysi = chrysene-5,6-quinone diimine), and the light switch behavior of [Ru(bpy)2(dppz)](2+) (dppz = dipyrido[3,2-a:2',3'-c]phenazine). In one approach, complexes bearing analogues of chrysi incorporating hydrogen-bonding functionality similar to dppz were synthesized. While the complexes show luminescence only at low temperatures (77 K), competition experiments with [Ru(bpy)2(dppz)](2+) at ambient temperatures reveal that the chrysi derivatives preferentially bind DNA mismatches. In another approach, various substituents were introduced onto the dppz ligand to increase its steric bulk for mismatch binding while maintaining planarity. Steady state luminescence and luminescence lifetime measurements reveal that these dppz derivative complexes behave as DNA "light switches" but that the selectivity in binding and luminescence with mismatched/abasic versus well-matched DNA is not high. In all cases, luminescence depends sensitively upon structural perturbations to the dppz ligand.

Heteroditopic receptors for ion-pair recognition.

Ion-pair recognition is a new field of research emerging from cation and anion coordination chemistry. Specific types of heteroditopic receptor designs for ion pairs and the complexity of ion-pair binding are discussed to illustrate key concepts such as cooperativity. The importance of this area of research is reflected by the wide variety of potential applications of ion-pair receptors, including applications as membrane transport and salt solubilization agents and sensors.

M-CPOnes: transition metal complexes with cyclopropenone-based ligands for light-triggered carbon monoxide release.

A new class of CO-releasing molecules, M-CPOnes, was prepared combining cyclopropenone-based ligands for CO release with the modular scaffold of transition metal complexes. In proof-of-concept studies, M-CPOnes based on ZnII, FeII and CoII are stable in the dark but undergo light-triggered CO release with the cyclopropenone substituents and metal ions enabling tuning of the photophysical properties. Furthermore, the choice of metal allows the use of different spectroscopic methods to monitor photodecarbonylation from fluorescence spectroscopy to UV/vis spectroscopy and paramagnetic NMR spectroscopy. The modularity of M-CPOnes from the metal ion to the cyclopropenone substitution and potential for further functionalisation of the ligand make M-CPOnes appealing for tailored functionality in applications.

The Dynamic Covalent Chemistry of Amidoboronates: Tuning the rac5 /rac6 Ratio via the B-N and B-O Dynamic Covalent Bonds.

Amidoboronates were prepared as a mixture of up to three isomers (rac5 , meso5 and rac6 ) from the reductive coupling of N-aryl iminoboronates with either cobaltocene or decamethylcobaltocene in acetonitrile. The interconversion of rac5 and rac6 isomers via rearrangement of their dynamic covalent B-N bonds was investigated in solution by redissolving isolated crystals. The aniline para substituent and catechol within the amidoboronates tuned the rac5 /rac6 ratio; the rac6 isomer predominated for amidoboronates based on pyrocatechol, ranging from a ratio of 0 : 1 with electron-withdrawing Cl substituents to 0.5 : 0.5 for electron-donating NMe2 substituents. No interconversion was observed for the rac5 isomers of amidoboronates based on tetrachlorocatechol. Furthermore, the rac5 /rac6 distribution was altered by catechol exchange of pyrocatechol for tetrachlorocatechol exploiting the dynamic covalent B-O bonds and the rac5 isomer was the major isomer following exchange.

The Dynamic Covalent Chemistry of Amidoboronates: Tuning the rac5 /rac6 Ratio via the B-N and B-O Dynamic Covalent Bonds.

Invited for this month's cover is the group of Anna J. McConnell and Christian Näther from Christian-Albrechts-Universität zu Kiel, Germany. The cover picture shows an amidoboronate puzzle divided into four quarters that represent four possible amidoboronates. How do these amidoboronates interconvert? The right combination of aniline (yellow circles) and catechol (grey and purple circles) pieces solves this conundrum and the amidoboronates interconvert via dynamic covalent B-N (left to right) and B-O bonds (top to bottom). More information can be found in the Research Article by Anna J. McConnell and co-workers.

Managing research throughout COVID-19: Lived experiences of supramolecular chemists.

The international Women in Supramolecular Chemistry network believes that taking an area-specific approach effectively supports equality, diversity, and inclusion. Science lacks diversity, and this is intersectional. We share effects of coronavirus disease 2019 (COVID-19) by triangulating findings from an online survey, a collaborative autoethnography, and reflective group research meetings. We show how qualitative research with the community offers insights into challenges and supports individuals, and we demonstrate that research leaders have often taken responsibility for their teams' mental health and well-being at the cost of their own.

Kinetic studies exploring the role of anion templation in the slippage formation of rotaxane-like structures.

The first examples of the slippage formation of rotaxane-like structures in the presence of an anion template are reported between a macrocycle, synthesised by exploiting Eglinton coupling, and stoppered pyridinium axle components. The role of the anion template in the slippage process has been explored by kinetic studies. (1)H NMR spectroscopic investigations reveal the slippage species formed are not rotaxanes but pseudorotaxanes with some rotaxane character. The anion template significantly influences the amount of rotaxane character and the rate of slippage. Importantly, the fastest slippage rates, k(on), are achieved with the non-coordinating hexafluorophosphate anion, whereas the slowest slippage off rates, k(off), are observed in the presence of coordinating anions, such as chloride. Since the k(off) rates are significantly smaller than the k(on) rates in the presence of coordinating anions, these anions act as templates favouring formation of the slippage species thermodynamically. Consequently, the resulting pseudorotaxanes with coordinating anions have greater rotaxane character. Two strategies for converting the slippage pseudorotaxanes into rotaxanes using hydrogenation or complexation with cobalt carbonyl are investigated.

Calix[4]arene-based rotaxane host systems for anion recognition.

The synthesis, structure and anion binding properties of the first calix[4]arene-based [2]rotaxane anion host systems are described. Rotaxanes 9.Cl and 12.Cl, consisting of a calix[4]arene functionalised macrocycle wheel and different pyridinium axle components, are prepared via adaption of an anion templated synthetic strategy to investigate the effect of preorganisation of the interlocked host's binding cavity on anion binding. Rotaxane 12.Cl contains a conformationally flexible pyridinium axle, whereas rotaxane 9.Cl incorporates a more preorganised pyridinium axle component. The X-ray crystal structure of 9.Cl and solution phase (1)H NMR spectroscopy demonstrate the successful interlocking of the calix[4]arene macrocycle and pyridinium axle components in the rotaxane structures. Following removal of the chloride anion template, anion binding studies on the resulting rotaxanes 9.PF(6) and 12.PF(6) reveal the importance of preorganisation of the host binding cavity on anion binding. The more preorganised rotaxane 9.PF(6) is the superior anion host system. The interlocked host cavity is selective for chloride in 1:1 CDCl(3)/CD(3)OD and remains selective for chloride and bromide in 10 % aqueous media over the more basic oxoanions. Rotaxane 12.PF(6) with a relatively conformationally flexible binding cavity is a less effective and discriminating anion host system although the rotaxane still binds halide anions in preference to oxoanions.