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.

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.

Fast, non-eccentrically loaded exercise worsens tendinopathic healing responses in a murine model.

OBJECTIVE: To advance the understanding of how alterations in exercise speed and grade (flat vs 17° incline or decline) affect the quality of tendon healing, and to determine if a biomarker relationship exists between serum levels of a ColX breakdown product (CXM) and animals exposed to treadmill running protocols. ANIMALS: 35 male mice (C57BL/6J), 8 weeks of age. PROCEDURES: Mice were preconditioned on a treadmill for 14 days. Tendinopathy was then induced by 2 intra-tendinous TGFß1 injections followed by randomization into 7 exercise groups. Exercise capacity and objective gait analysis were measured weekly. Mice were euthanized and histopathologic analysis and evaluation of serum CXM levels were performed. Statistics were conducted using a 2-way ANOVA (exercise capacity), Mixed Effects Model (gait analysis, effect of preconditioning), and 1-way ANOVA (gait analysis, the effect of injury, and rehabilitation normalized to baseline; CXM serum analysis), all with Tukey post hoc tests and significance set to P < .05. RESULTS: Exercise at a fast-flat speed demonstrated inferior tendinopathic healing at the cellular level and impaired stance braking abilities, which were compensated for by increased propulsion. Mice exposed to exercise (at any speed or grade) demonstrated higher systemic levels of CXM than those that were cage rested. However, no ColX immunostaining was observed in the Achilles tendon or calcaneal insertion. CLINICAL RELEVANCE: Exercise at a fast speed and in absence of eccentric loading components (incline or decline) demonstrated inferior tendinopathic healing at the cellular level and impaired braking abilities that were compensated for by increased propulsion.

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.

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.

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.

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.

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.

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.

Untargeted metabolomics analysis identifies creatine, myo-inositol, and lipid pathway modulation in a murine model of tendinopathy.

Tendinopathy has been broadly characterized as alterations in cell proliferation, extracellular matrix turnover/synthesis, and inflammatory alterations. However, the underlying glucose metabolism pathways which contribute to these responses have not been well explored. The potential link between glucose metabolism and tendon pathology is interesting from a global standpoint since the development of spontaneous tendinopathy is associated with systemic metabolic disorders including diabetes mellitus. Therefore, the overarching goal of this study was to understand the potential pathogenic role of glucose metabolism-driven mechanisms in the development of tendinopathy. To test this, we have utilized an untargeted metabolomics approach to discover pathways which may be altered following tendinopathic injury and treadmill running in an established murine model of TGF-ß1 induced tendinopathy. While specific tendon glucose alterations were not observed via metabolomics or 18 F-fluoroeoxyglucose (FDG) positron emission tomography/microcomputed tomography imaging (18 F-FDG PET/CT), metabolites including creatinine, D-chiro-inositol, and lipids were dysregulated following tendon injury. As novel pathways for manipulation, the creatine pathway, myo-inositol pathway, and lipid signaling may lead to the development of enhanced preventative strategies and therapeutic options for all patients who suffer from tendon-related injuries.

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.

Supramolecular Chemistry: Young Talents and their Mentors.

Celebrating Supramolecular Chemistry and Mentoring: ChemPlusChem is pleased to publish a Special Collection on Supramolecular Chemistry: Young Talents and their Mentors, guest-edited by Anna McConnell, Cally Haynes, Claudia Caltagirone, and Jennifer Hiscock. The Special Collection features recent developments in supramolecular chemistry and highlights mentoring relationships between emerging investigators and their mentors.

From Heteroditopic to Multitopic Receptors for Ion-Pair Recognition: Advances in Receptor Design and Applications.

Ion-pair recognition has emerged from cation and anion recognition and become a diverse and active field in its own right. The last decade has seen significant advances in receptor design in terms of the types of binding motifs, understanding of cooperativity and increase in complexity from heteroditopic to multitopic receptors. As a result, attention has turned to applying this knowledge to the rational design of ion-pair receptors for applications in salt solubilisation and extraction, membrane transport and sensing. This Review highlights recent progress and developments in the design and applications of heteroditopic and multitopic receptors for ion-pair recognition.

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+ .

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.

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.