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Four ‐ faced Janus, the god of transitions, now permits interconversion of two mirror images of a P ‐ phenyl ‐ phosphabarbaralane via two orthogonal mechanisms at the same asymmetric center; a Walden ‐ type inversion of a phosphonium salt and a Cope rearrangement of its caged cyclic hydrocarbon skeleton. More information can be found in the Full Paper by K. Nikitin and D. G. Gilheany et al. on page 2332 ff. [ABSTRACT FROM AUTHOR]

The present study reports the results of structural and mechanical analysis, as well as proteins release kinetics and osteointegration in mice craniotomy model of highly porous PEEK (PolyEther Ether Ketone) and PEEK/HA (PolyEther Ether Ketone/HydroxyApatite) biomimetic scaffolds loaded with Escherichia coli -derived recombinant Bone Morphogenetic Protein-2 (BMP-2) and ErythroPOietin (EPO). Porous scaffolds were obtained by thermopressing with NaCl as a pore-forming filler. Two fractions of pore-forming filler were used to imitate natural trabecular bone tissue by making a preferential porosity using large fraction and creating an extended surface and special microrelief using small fraction. Hydroxyapatite (HA) was added up to 20% to activate bioinert PEEK providing loading of recombinant growth factors and osteointegration as well as sufficient level of mechanical properties imitating human trabecular bone. Unexpectedly, the non-activated PEEK produced by our technology was also able to spontaneously bind both BMP-2 and EPO. Loading of both BMP-2 and EPO to both types of implants resulted in enhanced neoosteogenesis and angiogenesis in a critical-size cranial defect model in mice in 3–6 weeks. Considering good mechanical characteristics and excellent osteoinductive and angiogenic properties, both materials in combination with BMP-2 and EPO can find their application in regenerative medicine. Image 1 • Novel biomimetic PEEK/HA scaffold for reconstructive surgery was developed. • PEEK/HA scaffold with 80% porosity and special microrelief mimics trabecular bone. • Scaffold provides tissue ingrowth on model of critical-sized cranial bone defects in mice. • BMP-2 and EPO enhance neoosteogenesis and angiogenesis. • Non-activated PEEK is able to spontaneously bind both BMP-2 and EPO. [ABSTRACT FROM AUTHOR]

A promising direction for the replacement of expanded bone defects is the development of bioimplants based on synthetic biocompatible materials impregnated with growth factors that stimulate bone remodeling. Novel biomimetic highly porous ultra-high molecular weight polyethylene (UHMWPE)/40% hydroxyapatite (HA) scaffold for reconstructive surgery with the porosity of 85 ± 1% vol. and a diameter of pores in the range of 50–800 μm was developed. The manufacturing process allowed the formation of trabecular-like architecture without additional solvents and thermo-oxidative degradation. Biomimetic UHMWPE/HA scaffold was biocompatible and provided effective tissue ingrowth on a model of critical-sized cranial defects in mice. The combined use of UHMWPE/HA with Bone Morphogenetic Protein-2 (BMP-2) demonstrated intensive mineralized bone formation as early as 3 weeks after surgery. The addition of erythropoietin (EPO) significantly enhanced angiogenesis in newly formed tissues. The effect of EPO of bacterial origin on bone tissue defect healing was demonstrated for the first time. The developed biomimetic highly porous UHMWPE/HA scaffold can be used separately or in combination with rhBMP-2 and EPO for reconstructive surgery to solve the problems associated with difference between implant architecture and trabecular bone, low osteointegration and bioinertness. Unlabelled Image • Novel biomimetic UHMWPE/HA scaffold for reconstructive surgery was developed. • UHMWPE/HA scaffold with 90% porosity mimics trabecular bone architecture. • Scaffold provides tissue ingrowth on model of critical-sized cranial bone defects in mice. • UHMWPE/HA + BMP2 led to intensive mineralized bone formation in 3 weeks. • EPO of bacterial origin enhances angiogenesis on defect healing. [ABSTRACT FROM AUTHOR]

A new dual-functional implant based on gellan-xanthan hydrogel with calcium-magnesium silicate ceramic diopside and recombinant lysostaphin and bone morphogenetic protein 2 (BMP-2)-ray is developed. In this composite, BMP-2 is immobilized on microparticles of diopside while lysostaphin is mixed directly into the hydrogel, providing sustained release of BMP-2 to allow gradual bone formation and rapid release of lysostaphin to eliminate infection immediately after implantation. Introduction of diopside of up to 3% (w/v) has a negligible effect on the mechanical properties of the hydrogel but provides a high sorption capacity for BMP-2. The hydrogels show good biocompatibility and antibacterial activity. Lysostaphin released from the implants over a 3 h period efficiently kills planktonic cells and completely destroys 24 h pre-formed biofilms of Staphylococcus aureus. Furthermore, in vivo experiments in a mouse model of critically-sized cranial defects infected with S. aureus show a complete lack of osteogenesis when implants contain only BMP-2, whereas, in the presence of lysostaphin, complete closure of the defect with newly formed mineralized bone tissue is observed. Thus, the new implantable gellan-xanthan hydrogel with diopside and recombinant lysostaphin and BMP-2 shows both osteogenic and antibacterial properties and represents a promising material for the treatment and/or prevention of osteomyelitis after bone trauma., (© 2024 Wiley‐VCH GmbH.)

In this study, Pt(0) microscrolls are synthesized on polished Ni via galvanic replacement reaction (GRR). Employing in situ optical microscopy, the dynamic motion of the catalytic microscrolls as micromotors in H 2 O 2 solutions is revealed. This method offers a rapid fabrication of scrolls from diverse noble metals and alloys.

P -Stereomutation of phosphine oxides is extremely slow. We show that it is catalysed by chlorophosphonium salts (CPS) which can directly be formed in the system in situ . The racemization of phosphine oxides at ambient conditions catalysed by 1 mol% of CPS takes 1-2 hours and can be arrested by additon of a primary alcohol. The process probably proceeds via the development of oxodiphosphonium P-O-P species.

High efficiency of hybrid implants based on calcium-magnesium silicate ceramic, diopside, as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously using the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using in vivo bioreactor principle in the patient's own body, effectiveness of ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At the dose of 7 μg of BMP-2 per implant, dense agglomeration of cells, probably skeletal muscle satellite precursor cells, was observed one week after implantation with areas of intense chondrogenesis, initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed covered with periosteum and mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputed tomography data showed significant increase of the relative bone volume, number of trabeculae, and bone tissue density in the group of mice with BMP-2-containing implant in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities with required size and shape, and that BMP-2 is obtained by synthesis in E. coli cells and is relatively inexpensive, further development of the in vivo bioreactor model based on the hybrid implants constructed from BMP-2, diopside, and xenogenic DBM seems promising.

Calcium-magnesium silicate ceramics, diopside, is a promising material for use in bone plastics, but until now the possibility of its use as a carrier of recombinant bone morphogenetic protein-2 (BMP-2) has not been studied, as well as the features of reparative osteogenesis mediated by the materials based on diopside with BMP-2. Powder of calcium-magnesium silicate ceramics was obtained by solid-state synthesis using biowaste - rice husks and egg shells - as source components. Main phase of the obtained ceramics was diopside. The obtained particles were irregularly shaped with an average size of about 2.3 μm and ~20% porosity; average pore size was about 24 nm, which allowed the material to be classified as mesoporous. Diopside powder adsorbs more than 150 μg of recombinant BMP-2 per milligram, which exceeds binding capacity of hydroxyapatite, a calcium-phosphate ceramic often used in hybrid implants, by more than 3 times. In vitro release kinetics of BMP-2 was characterized by a burst release in the first 2 days and a sustained release of approximately 0.4 to 0.5% of the loaded protein over the following 7 days. In vivo experiments were performed with a mouse model of cranial defects of critical size with implantation of a suspension of diopside powder with/without BMP-2 in hyaluronic acid incorporated into the disks of demineralized bone matrix with 73-90% volume porosity and macropore size from 50 to 650 μm. Dynamics of neoosteogenesis and bone tissue remodeling was investigated histologically at the time points of 12, 21, 48, and 63 days. Diopside particles were evenly spread in the matrix and caused minimal foreign body reaction. In the presence of BMP-2 by the day 63 significant foci of newly formed bone tissue were formed in the implant pores with bone marrow areas, moreover, large areas of demineralized bone matrix in the implant center and maternal bone at the edges were involved in the remodeling. Diopside could be considered as a promising material for introduction into hybrid implants as an effective carrier of BMP-2.

Purpose: Triple therapy comprising a long-acting muscarinic antagonist, long-acting β 2 -agonist and inhaled corticosteroid is recommended for patients with chronic obstructive pulmonary disease (COPD) who continue to experience frequent exacerbations or symptoms whilst receiving dual therapy. Adherence and persistence to multiple-inhaler triple therapy (MITT) is known to be poor. This study assessed comparative adherence to single-inhaler triple therapy (SITT) versus MITT in a real-world setting in England., Patients and Methods: This was a retrospective cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics [HES] Admitted Patient Care) data to identify patients with COPD who were newly initiated on SITT or MITT between November 2017 and June 2019. Eligible patients were aged ≥35 years and had a forced expiratory volume in 1 second/forced vital capacity <0.7, linkage to HES and continuous registration with a general practitioner for 12 months pre- and 6 months post-initiation. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Adherence was measured using the proportion of days covered by days' supply of SITT or MITT prescriptions. Persistence was measured with a gap of >30 days between the end of a prescription and the following refill used to determine non-persistence., Results: Overall, 4080 SITT and 6579 MITT users comprised the study cohort. After weighting, the baseline characteristics between the cohorts were comparable (absolute standardized mean difference <10%). SITT users had significantly higher adherence than MITT users at 6, 12, and 18 months post-initiation (p<0.001 for all comparisons). Median persistence was higher among SITT users than MITT users (5.09 months vs 0.99 months)., Conclusion: Patients with COPD in England initiating SITT had significantly better adherence and persistence compared with MITT initiators. These improvements continued at least 18 months following treatment initiation., Competing Interests: Kieran J Rothnie, Alexandrosz Czira, Chris Compton, Kirill Nikitin, Raj Sharma, and Afisi S Ismaila are employees of and/or hold stocks/shares in GSK. Neil Snowise is a previous employee of GSK and holds GSK stocks/shares. Victoria Banks, Robert Wood, Theo Tritton, Olivia Massey, and Rosie Wild are employees of Adelphi Real World. Adelphi Real World received funding from GSK to conduct the study. David MG Halpin reports personal fees from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Aerogen, Chiesi, CSL Behring, and GSK, personal fees and non-financial support from Novartis, and personal fees from Pfizer and Sanofi. Claus F Vogelmeier has received research grants from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, and Grifols, and has given presentations at symposia and/or served on scientific advisory boards sponsored by Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, Grifols, Menarini, Novartis, and Nuvaira. The authors report no other conflicts of interest in this work., (© 2022 Halpin et al.)

The use of real-world evidence (RWE) studies, including pragmatic randomised controlled trials (RCTs; randomised RWE studies), to aid the development of treatment guidelines, is gradually becoming a mainstay within clinical practice. RWE is an integral part of patient-driven decision-making and offers important value to add complimentary evidence to traditional RCTs; these provide a more well-rounded view of the benefits to patient-reported outcomes and improve the external validity of a given treatment versus findings from traditional RCTs alone. Discussions in recent scientific workshops explored the importance of pragmatic RCTs in optimising guideline development and patient care in chronic obstructive pulmonary disease (COPD) and asthma. The Salford Lung Study in patients with COPD (NCT01551758) and asthma (NCT01706198) were the world's first prelicence pragmatic RCTs that compared novel investigational treatments with existing COPD and asthma treatments and, more recently (2021), RWE studies have been used by the American Thoracic Society and the US Food and Drug Administration to support the approval of an immunosuppressant drug in patients receiving lung transplants. This highlights the importance of RWE data in supporting clinical guideline development and emphasises the advantages for the use of pragmatic RCTs in guiding clinical practice., Competing Interests: Competing interests: NDB reports grants and personal fees from GSK, Novartis and Almirall/AstraZeneca, and congress attendance fees from Boehringer-Ingelheim. KN and GC are employees of and shareholders in GSK. NGS is a former employee of GSK. RS reports previous honoraria/sponsorship for consultancy work, lecturing and educational events unrelated to this workshop from GSK, Cogora, Pharman, Chiesi, Boehringer Ingelheim, Teva, AstraZeneca and the Centre for Pharmacy Postgraduate Education, and is a member of the National Institute for Health and Care Excellence COPD guidelines committee and the British Thoracic Society specialist advisory group. ADS reports grants, personal fees and other financial activities from AstraZeneca, Bayer, GSK, Gilead, Novartis, Pfizer, Teva and Chiesi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A new class of biaryl chiral ligands derived from 1,2-diaminocyclohexane (1,2-DACH) has been designed to enable the asymmetric addition of aliphatic and, for the first time, aromatic Grignard reagents to ketones for the preparation of highly enantioenriched tertiary alcohols (up to 95% ee). The newly developed ligands L12 and L12' together with the previously reported L0 and L0' define a set of complementary chiral promoters, which provides access to the modular construction of a broad range of structurally diverse non-racemic tertiary alcohols, bearing challenging quaternary stereocenters. The present advancements bring to completion our asymmetric Grignard methodology by expanding the scope to aromatic organomagnesium reagents, while facilitating its implementation in organic synthesis thanks to improved synthetic routes for the straightforward access to the chiral ligands. The synthetic utility of the method has been demonstrated by the development of a novel and highly enantioselective formal synthesis of the antihistamine API clemastine via intermediate ( R )-3a. Exploiting the power of the 3-disconnection approach offered by the Grignard synthesis, ( R )-3a is obtained in 94% ee with ligand ( R , R )-L12. The work described herein marks the finalization of our ongoing effort towards the establishment of an effective and broadly applicable methodology for the asymmetric Grignard synthesis of chiral tertiary alcohols., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Osteoplastic materials PLA/PCL/HA and PHB/HA and scaffolds with a highly porous structure based on them with potential applications in regenerative medicine have been obtained by solvent casting with thermopressing and salt leaching for PLA-based samples and solid-state mixing with subsequent thermopressing and salt leaching for PHB-based samples. The scaffolds were characterized by SEM-EDX, DSC, FTIR spectroscopy, mechanical tests in compression, measurement of the contact angle, in vitro studies, including loading by recombinant BMP-2 and EPO and their release kinetics, and in vivo studies on a model of regeneration of critical-sized cranial defects in mice. Biomimetic scaffolds with micropores sizes ranged from 300 to 500 μm and volume porosity of 70% imitate trabecular bone's structure and have increased hydrophilicity to achieve osteoconductive properties. Mechanical characteristics correspond to native trabecular bone. Elastic modulus - key mechanical characteristics of bone implants - showed the values of 0.15 ± 0.04 and 0.18 ± 0.08 GPa for PLA/PCL/HA and PHB/HA scaffolds, respectively. Both materials have high biocompatibility and can be used together with recombinant proteins BMP-2 and EPO. Introduction of BMP-2 leads to induction of new bone formation, introduction of EPO results in increased angiogenesis in the implantation area. The obtained scaffolds with recombinant proteins can be used as bone implants for reconstruction of defects of lightly or non-loaded bones., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Directional internal rotation in molecular systems, generally controlled by chirality, is known to occur in natural and artificial systems driven by light or fueled chemically, but spontaneous directional molecular rotation is believed to be forbidden. We have designed a molecular rotor, whereby ferrocene and triptycene linked by a methylene bridge provide two rotational degrees of freedom. On the basis of experimental observations, in conjunction with computational data, we show that the two different modes of rotation are strongly coupled and the spatial orientation of the bistable ferrocene moiety controls the barrier to its own rotation about the triptycene axis. It is proposed that the barrier to clockwise 120° rotation across each individual triptycene blade is lower in the M -enantiomer and for counterclockwise 120° rotation, it is lower in its P -counterpart. These findings demonstrate the possibility of locally preferred thermal directional intramolecular rotation for each dynamically interconverting enantiomer.

Despite common perception, the use of strong bases in Wittig chemistry is utterly unnecessary: we report a series of novel ion-pair phosphonium carboxylate reagents which are essentially "storable ylides". These reagents are straightforwardly prepared in excellent yields, and their fluxional nature permits clean olefination of a broad range of aldehydes and even hemiacetals.

Pd-catalysed Stille and Suzuki cross-couplings were used to prepare 9-(3-indenyl)-, 6, and 9-(2-indenyl)-anthracene, 7; addition of benzyne led to the 9-Indenyl-triptycenes, 8 and 9. In 6, [4 + 2] addition also occurred to the indenyl substituent. Reaction of 6 through 9 with Cr(CO) 6 or Re 2 (CO) 10 gave their M(CO) 3 derivatives, where the Cr or Re was complexed to a six- or five-membered ring, respectively. In the 9-(2-indenyl)triptycene complexes, slowed rotation of the paddlewheel on the NMR time-scale was apparent in the η 5 -Re(CO) 3 case and, when the η 6 -Cr(CO) 3 was deprotonated, the resulting haptotropic shift of the metal tripod onto the five-membered ring also blocked paddlewheel rotation, thus functioning as an organometallic molecular brake. Suzuki coupling of ferrocenylboronic acid to mono- or dibromoanthracene yielded the ferrocenyl anthracenes en route to the corresponding triptycenes in which stepwise hindered rotations of the ferrocenyl groups behaved like molecular dials. CuCl 2 -mediated coupling of methyl- and phenyl-indenes yielded their rac and meso 2,2'-biindenyls; surprisingly, however, the apparently sterically crowded rac 2,2'-Bis(9-triptycyl)biindenyl functioned as a freely rotating set of molecular gears. The predicted high rotation barrier in 9-phenylanthracene was experimentally validated via the Pd-catalysed syntheses of di(3-fluorophenyl)anthracene and 9-(1-naphthyl)-10-phenylanthracene., Competing Interests: The authors declare no conflict of interest.

Detailed mechanistic information is crucial to our understanding of reaction pathways and selectivity. Dynamic exchange NMR techniques, in particular 2D exchange spectroscopy (EXSY) and its modifications, provide indispensable intricate information on the mechanisms of organic and inorganic reactions and other phenomena, for example, the dynamics of interfacial processes. In this Review, key results from exchange NMR studies of small molecules over the last few decades are systemised and discussed. After a brief introduction to the theory, the key types of dynamic processes are identified and fundamental examples given of intra- and intermolecular reactions, which, in turn, could involve, or not, bond-making and bond-breaking events. Following that logic, internal molecular rotation, intramolecular stereomutation and molecular recognition will first be considered because they do not typically involve bond breaking. Then, rearrangements, substitution-type reactions, cyclisations, additions and other processes affecting chemical bonds will be discussed. Finally, interfacial molecular dynamics and unexpected combinations of different types of fluxional processes will also be highlighted. How exchange NMR spectroscopy helps to identify conformational changes, coordination and molecular recognition processes as well as quantify reaction energy barriers and extract detailed mechanistic information by using reaction rate theory in conjunction with computational techniques will be shown., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Type 2 diabetes (T2D) is a socially significant disease that affects millions of patients. There were an estimated 366 million people with this disease in 2011, and, according to the forecast, approximately 552 million will be affected by this disease in 2030. It is well known that the primary diagnosis and treatment of a patient with this disease are quite expensive. What should be done to make it possible for a patient to monitor his own state and provide treatment in his own home using telemedicine? To solve this problem, an alternative concept for the diagnosis, monitoring, and treatment at the basis of traditional Chinese medicine combined with mathematical methods of data processing has been used., Methods/design: To assess the pattern thresholds of acupuncture channels of heat sensitivity in patients with T2D, the Akabane test was performed on 160 men and 243 women (total 696 tests), including the dynamics of surveillance. For comparison, a group of healthy individuals comprising 116 men and 277 women also participated., Results: It was found that the main difference between patients with T2D and the healthy individuals is the presence of a pronounced asymmetry between the right and left branches of the canals, primarily in the digestive system. At the same time, the level of asymmetry increases with the increase in the glycemic level. This dependence allows for the early diagnosis of T2D. Moreover, a targeted stimulation of the definite channels with a high level of asymmetry based on the individual calculations can decrease the glycemic level., Conclusion: The combination of the Akabane test with the use of mathematical analysis in patients with T2D makes it possible to trace the entire chain of carbohydrate metabolism at an individual level and to identify the compensatory mechanisms for more effective treatment of reflexotherapy methods. This kind of treatment and monitoring can also be performed by the patient independently in his own home., (Copyright © 2018. Published by Elsevier B.V.)

The complex fluxional interconversions between otherwise very similar phosphonium bromides and chlorides R 3 PX + X - (R=Alk, Ar, X=Cl or Br) were studied by NMR techniques. Their energy barriers are typically ca. 11 kcal mol -1 , but rise rapidly as bulky groups are attached to phosphorus, revealing the importance of steric factors. In contrast, electronic effects, as measured by Hammett analysis, are modest (ρ 1.46) but still clearly indicate negative charge flow towards phosphorus in the transition state. Most significantly, detailed analysis of the exchange pathways unequivocally, and for the first time in any such process, shows that nucleophilic attack of the nucleophilic anion on the tetrahedral centre results in inversion of configuration., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

P-Alkoxyphosphonium (AP) chlorides were generated by reacting P-chlorophosphonium chlorides with alcohols. Their well-known spontaneous Arbuzov-type collapse leading to phosphine oxides was studied and its rate found to be dependent on a number of factors in an unexpected fashion: it is inversely proportional to the initial concentration and it shows strong dependence on the acidity of the media but is not very sensitive to the presence of base. To explain these observations, we evoke a self-inhibition model with the formation of the less nucleophilic hydrodichloride anion HCl 2 in solution. Detailed analysis of the kinetic data yields the association constant (K=3×10 2  m -1 ) of the putative HCl 2 species in chloroform. Experimental observations for the collapse of highly enriched diastereomeric alkoxyphosphonium (DAP) chlorides are fully analogous to the achiral AP also implying the involvement of HCl 2 anions. Moreover, crystallisation of a highly enriched DAP salt derived from (-)-menthol furnished, for the first time, crystals of individual (R P )-DAP hydrodichloride as confirmed by X-ray diffractometry. Importantly, the P-configuration and detailed conformation of the DAP moiety is in good agreement with DFT-level computational results. The thermal collapse of (R P )-DAP⋅HCl 2 proceeds with complete retention of the P-configuration furnishing the phosphine oxide of exceptional enantiomeric purity., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Treatment of β-naphthil dihydrazone, 1, with silver oxide yields di(β-naphthyl)acetylene, 2, which undergoes Diels-Alder cycloaddition with tetra(β-naphthyl)cyclopentadienone, 4, to give hexa(β-naphthyl)benzene, 5, upon decarbonylation. Molecules 1, 2 and 4 have been characterised by X-ray crystallography, but hexa(β-naphthyl)benzene exhibits rotational disorder of the peripheral substituents. Nevertheless, calculations at the density functional level reveal the favoured structure of 5 to be a molecular propeller, in which the eight possible rotamers are essentially iso-energetic. Variable-temperature NMR spectroscopy studies yield a naphthyl rotational barrier of approximately 17 kcal mol -1 , similar to that previously found for meta-substituted phenyl groups. Enantiomerisation of hexa(β-naphthyl)benzene engendered by rotation of a single naphthyl ring has been studied by DFT calculations, and the process has been represented pictorially., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The title triptycene, 6, has been isolated as the product of 9,10-cycloaddition of benzyne to 9,10-diferrocenyl-2,6-di-tert-butylanthracene, 5, whose X-ray crystal structure is reported. Each ferrocenyl unit in 6 has access to the same three non-equivalent molecular environments, and their rotations relative to the molecular paddlewheel give rise to six slowly interconverting atropisomers. Their dynamic behaviour in solution is a challenging NMR puzzle that can be successfully solved by taking advantage of the recently described very large diamagnetic anisotropy of the ferrocenyl moiety, together with the C2 symmetry of particular atropisomers. Application of one- and two-dimensional NMR techniques over a range of temperatures together, with a detailed analysis of the homo- and heteronuclear correlations in 6, resulted in unequivocal mapping of the 99 (1)H and 162 (13)C positions in the six interconverting systems. Variable-temperature 2D-EXSY measurements revealed that, while the stability of the atropisomers is almost identical, they are separated by energy barriers which the ferrocenyls must overcome in the course of their interconversions. The heights of two different rotational barriers have been identified and these experimental findings are in good agreement with DFT calculations., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Prototropic rearrangement of the Diels-Alder adduct (3a) of 9-ferrocenylanthracene and 1,4-benzoquinone potentially furnishes 9-ferrocenyl-1,4-dihydroxytriptycene (3b) incorporating a C(2v) symmetrical paddlewheel moiety. However, reaction of 3a with HBF(4) unexpectedly yields instead 9-ferrocenyl-10-(2,5-dihydroxyphenyl)anthracene (4) via cleavage of the C9-C12 bond to generate initially a ferrocenyl-stabilized cation. Treatment of 3a with sodium hydride and iodomethane yields 1,4-dimethoxy-9-ferrocenyltriptycene (3c) in high yield but, surprisingly, also leads to fission of the C9-C12 bond resulting, after methylation, in the formation of 9-hydroxy-9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)dihydroanthracene (12), which readily dehydrates on silica to form 9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)anthracene (8). The X-ray crystal structures of 3a, 3c and 4 are reported., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The calculated phenyl rotation barrier in 9-phenylanthracene has been reported as ~21 kcal mol(-1), but experimental verification of this barrier is limited by its intrinsic symmetry. V-T NMR indicated the barrier to interconversion of the syn (C(2v)) and anti (C(2h)) rotamers of 9,10-bis(3-fluorophenyl)anthracene to be ~21 kcal mol(-1). Likewise, the V-T NMR spectra of 9-(1-naphthyl)-10-phenylanthracene reveal that the rotational barrier of the unsubstituted phenyl ring is at least 21 kcal mol(-1).

In [eta(6)-2-(9-triptycyl)-indene]tricarbonylchromium (2a), the indenyl-chromium moiety is linked directly to the axis of the three-bladed triptycene paddlewheel. However, the molecular structure of 2a reveals that there is no steric interaction between these components, and the paddlewheel is free to rotate. Accordingly, its NMR spectrum indicates the full equivalence of the blades of the triptycene. Deprotonation of the indene induces a haptotropic shift of the organometallic fragment from the six-membered to the five-membered ring of the indene and, in the sodium [eta(5)-2-(9-triptycyl)-indenyl]tricarbonylchromium salt (3a), so formed, rotation of the three-bladed molecular paddlewheel is now blocked by the bulky tripod. NMR data for 3a, and also for the isostructural eta(5)-Mn(CO)(3) and eta(5)-Re(CO)(3) complexes, 3b and 3c, respectively, reveal a 2:1 splitting of the blades of the triptycyl moiety, thus breaking its original threefold symmetry. The X-ray crystal structures of the chromium complex, 2a, and of the manganese and rhenium complexes, 3b and 3c, provide pictures of the system in both its "ON" and "OFF" states, whereby the M(CO)(3) tripod has moved about 2 A towards the triptycene, thus blocking its rotation. Comparison of the rotational barriers in 2-(9-triptycyl)indene (1) and its complexes 2 and 3, suggests that rotation of the paddlewheel can be slowed by a factor of approximately 10(8).

This paper describes novel host-guest systems comprising viologen cations (guests) and the derivatives of bis-para-phenylene-34-crown-10 (hosts) with anionic groups COO(-) or SO(3)(-). The structure of the resulting charge-compensated host-guest complexes, their association constants and their electrochemical behaviour have been studied. In the solid state, the viologen cations thread the negatively charged crown ethers forming electroneutral zwitterion-like [2]pseudorotaxane salts; in solution this threaded geometry is preserved. The association constants of [2]pseudorotaxane salts incorporating the 1,1'-diethylviologen moiety in solution are significantly higher than those of previously reported analogues. The extrapolated association free energies in non-aqueous media exceed -40 kJ mol(-1) at 25 degrees C. This significant increase of the interaction free energy makes these compounds stable even in aqueous solutions. The association constants of [2]pseudorotaxane salts incorporating sterically more hindered 1,1'-diethyl-3,3'-dimethylviologen moieties are significantly lower. Structurally related [2]rotaxane salts, in which the oppositely charged ionic components are mechanically interlocked, have been prepared in good yields. It has been shown that [2]rotaxane salts incorporating anti-isomers of bisfunctionalised crown ethers are cycloenantiomeric. In both [2]pseudorotaxane and [2]rotaxane salts, the electrostatic interactions between the viologen moieties and the negatively charged crown ethers lead to very significant negative shifts of viologen reduction potentials up to 450 mV. The findings of the present study are valuable for the design of nanoscale molecular electronic devices.

This paper reports a novel methodology for the conformational analysis of [2]rotaxanes. It combines NMR spectroscopic (COSY, NOESY and the recently reported paramagnetic line-broadening and suppression technique) and electrochemical techniques to enable a quantitative analysis of the co-conformations of interlocked molecules and the conformations of their components. This methodology was used to study a model [2]rotaxane in solution. This [2]rotaxane consists of an axle that incorporates an electron-poor, doubly positively charged viologen that threads an electron-rich crown ether. It has been shown that the axle of the [2]rotaxane in its dicationic state adopts a folded conformation in solution and the crown ether is localised at the viologen moiety. Following a one-electron reduction of viologen, the paramagnetic radical cation of the [2]rotaxane retains its folded conformation in solution. The data also demonstrate that in the radical cation the crown ether remains localised at the viologen, despite its reduced affinity for the singly reduced viologen. The combined quantitative NMR spectroscopic and electrochemical characterisation of the electromechanical function of the model [2]rotaxane in solution provides an important reference point for the study of switching in structurally related bistable [2]rotaxanes, which is the subject of the second part of this work.

Translational movement of the macrocycle in two structurally similar bistable [2]rotaxanes, which is induced by a four-step electrochemical process in solution, has been investigated by using a methodology developed in the preceding article (Chem. Eur. J. 2008, 14, 1107-1116). Both [2]rotaxanes contain a crown ether that can be accommodated by either of two interconnected viologen recognition sites. These sites are substantially different in terms of their affinity towards the crown ether and they possess considerably different electrochemical reduction potentials. The two [2]rotaxanes differ in the length and the rigidity of a bridge that links these sites. A combination of molecular mechanics modelling and NOE spectroscopy data provides information about the conformations of both [2]rotaxanes in the parent oxidation state when the crown ether exclusively populates the strong recognition site. To determine the population of the recognition sites at subsequent stages of reduction, a paramagnetic NMR technique and cyclic voltammetry were used. The key finding is that the flexibility of the connecting bridge element between the recognition sites interferes with shuttling of the crown ether in [2]rotaxanes. It can be demonstrated that the more flexible trimethylene bridge is folded, thus limiting the propensity of the crown ether to shuttle. Consequently, the crown ether populates the original site even in the second reduced state of the flexible [2]rotaxane. On the contrary, in the [2]rotaxane in which two viologen sites are connected by a larger and more rigid p-terphenylene bridge, the predominant location of the crown ether at the weak recognition site is achieved after just one single electron reduction.

The indenyltriptycenes, and , where the 3- or 2-indenyl, respectively, is attached at the 9-position of the triptycene, are attractive prototypes of molecular gearing systems that can also incorporate a brake. These molecules have been prepared from their respective indenylanthracenes, and , by the [4 + 2] cycloaddition of benzyne to the anthracene fragment, and the rotational barriers about the indenyl-triptycenyl single bonds in (12 kcal mol(-1)) and (<9 kcal mol(-1)) have been measured. The precursor anthracenes, and , were prepared by using palladium-catalysed coupling reactions. Unexpectedly, the Heck-type reaction of 9-bromoanthracene, , with indene leads to the formation of 3-indenylanthracene ; moreover, this process is accompanied by a novel palladium-catalysed carbocyclisation reaction leading to the indenophenanthrylene . The addition of benzyne to 9-(3-indenyl)anthracene, , yields the corresponding indenyltriptycene, , and, surprisingly, the anthracenyl methano-bridged phenanthrene . It has been demonstrated that 2-arylindenes can act as 1,3-dienes in the [4 + 2] cycloadditions of benzyne. The products , , and have been characterised by X-ray crystallography.

This paper describes the self-assembly of a heterosupramolecular system consisting of a tripodal [2]rotaxane adsorbed at the surface of a titanium dioxide nanoparticle. The tripodal [2]rotaxane consists of a dumbbell-shaped molecule, incorporating two electron-poor viologens, threading an electron-rich crown ether. The [2]rotaxane also incorporates a bulky tripodal linker group at one end and a bulky stopper group at the other end. The [2]rotaxane is adsorbed, via the tripodal linker group, at the surface of a titanium dioxide nanoparticle. The structure and function of the resulting hetero[2]rotaxane have been studied in detail by (1)H NMR spectroscopy and cyclic voltammetry. A key finding is that it is possible to electronically address and switch the above hetero[2]rotaxane.

This paper describes the self-assembly of a heterosupramolecular system consisting of a tripodal viologen, adsorbed at the surface of a titanium dioxide nanoparticle, that threads a crown ether to form a pseudorotaxane. The viologen, a 1,1'-disubstituted-4,4'-bipyridinium salt with a rigid tripodal anchor group, has been synthesized. This viologen is adsorbed at the surface of a titanium dioxide nanoparticle in solution. As intended, this tripodal viologen is both oriented normal to and displaced from the surface of the nanoparticle and threads a crown ether to form the heterosupramolecular complex. The threading of the crown ether by the tripodal viologen to form the above pseudorotaxane complex at the surface of a titanium dioxide nanoparticle has been studied by (1)H NMR, optical absorption spectroscopy, and cyclic voltammetry.