Metal Ions Trigger the Gelation of Cysteine-Containing Peptide-Appended Coordination Cages.

We report a series of coordination cages that incorporate peptide chains at their vertices, prepared through subcomponent self-assembly. Three distinct heterochiral tripeptide subcomponents were incorporated, each exhibiting an L-D-L stereoconfiguration. Through this approach, we prepared and characterized three tetrahedral metal-peptide cages that incorporate thiol and methylthio groups. The gelation of these cages wasprobed through the binding of additional metal ions, with the metal-peptide cages acting as junctions, owing to the presence of sulfur atoms on the peripheral peptides. Gels were obtained with cages bearing cysteine at the C-terminus. Our strategy for developing functional metal-coordinated supramolecular gels with a modular design may result in the development of materials useful for chemical separations or drug delivery.

A CuI6L4 Cage Dynamically Reconfigures to Form Suit[4]anes and Selectively Bind Fluorinated Steroids.

Simple organic ligands can self-assemble with metal ions to generate metal-organic cages, whose cavities bind guests selectively. This binding may enable new methods of chemical separation or sensing, among other useful functions. Here we report the preparation of a CuI6L4 pseudo-octahedral metal-organic cage, the ligands of which self-assemble from simple organic building blocks. Temperature, solvent, and the presence of different guests governed which structure predominated from a dynamic mixture of cage diastereomers with different arrangements of right- or left-handed metal vertices. Dissolution in dimethyl sulfoxide or the binding of tetrahedral guests led to a chiral tetrahedral T-symmetric framework, whereas low temperatures favored the achiral S4-symmetric diastereomer. Tetrahedral guests with long arms were encapsulated to form mechanically bonded suit[4]anes, with guest arms protruding out through host windows. The cage was also observed to bind fluorinated steroids, an important class of drug molecules, but not non-fluorinated steroids, providing the basis for new separation processes.

A case series of the Royal Perth Hospital cannula-first approach in the 'can't intubate, can't oxygenate' scenario.

At the Royal Perth Hospital, we have been developing and teaching a can't intubate, can't oxygenate (CICO) rescue algorithm for over 19 years, based on live animal simulation. The algorithm involves a 'cannula-first' approach, with jet oxygenation and progression to scalpel techniques if required in a stepwise fashion. There is little reported experience of this approach to the CICO scenario in humans. We present eight cases in which a cannula-first Royal Perth Hospital approach was successfully implemented during an airway crisis. We recommend that institutions teach and practice this approach; we believe it is effective, safe and minimally invasive when undertaken by clinicians who have been trained in it and have immediate access to the requisite equipment. The equipment is low cost, comprising a 14G Insyte cannula, saline, 5 ml syringe and a Rapid-O2. Training can be provided using low-fidelity manikins or part-task trainers.

A Diverse Array of Large Capsules Transform in Response to Stimuli.

The allosteric regulation of biomolecules, such as enzymes, enables them to adapt and alter their conformation to fit specific substrates, expressing different functionalities in response to stimuli. Different stimuli can also trigger synthetic coordination cages to change their shape, size, and nuclearity by reconfiguring the dynamic metal-ligand bonds that hold them together. Here we demonstrate an abiological system consisting of different organic subcomponents and ZnII metal ions, which can respond to simple stimuli in complex ways. A ZnII20L12 dodecahedron transforms to give a larger ZnII30L12 icosidodecahedron through subcomponent exchange, as an aldehyde that forms bidentate ligands is displaced in favor of one that forms tridentate ligands together with a penta-amine subcomponent. In the presence of a chiral template guest, the same system that produced the icosidodecahedron instead gives a ZnII15L6 truncated rhombohedral architecture through enantioselective self-assembly. Under specific crystallization conditions, a guest induces a further reconfiguration of either the ZnII30L12 or ZnII15L6 cages to yield an unprecedented ZnII20L8 pseudo-truncated octahedral structure. The transformation network of these cages shows how large synthetic hosts can undergo structural adaptation through the application of chemical stimuli, opening pathways to broader applications.

A Double-Walled Tetrahedron with AgI 4 Vertices Binds Different Guests in Distinct Sites.

A double-walled tetrahedral metal-organic cage assembled in solution from silver(I), 2-formyl-1,8-naphthyridine, halide, and a threefold-symmetric triamine. The AgI 4 X clusters at its vertices each bring together six naphthyridine-imine moieties, leading to a structure in which eight tritopic ligands bridge four clusters in an (AgI 4 X)4 L8 arrangement. Four ligands form an inner set of tetrahedron walls that are surrounded by the outer four. The cage has significant interior volume, and was observed to bind anionic guests. The structure also possesses external binding clefts, located at the edges of the cage, which bound small aromatic guests. Halide ions bound to the silver clusters were observed to exchange in a well-defined hierarchy, allowing modulation of the cavity volume. The principles uncovered here may allow for increasingly more sophisticated cages with silver-cluster vertex architectures, with post-assembly tuning of the interior cavity volume enabling targeted binding behavior.

Enantioselective fullerene functionalization through stereochemical information transfer from a self-assembled cage.

The regioselective functionalization of C60 remains challenging, while the enantioselective functionalization of C60 is difficult to explore due to the need for complex chiral tethers or arduous chromatography. Metal-organic cages have served as masks to effect the regioselective functionalization of C60. However, it is difficult to control the stereochemistry of the resulting fullerene adducts through this method. Here we report a means of defining up to six stereocentres on C60, achieving enantioselective fullerene functionalization. This method involves the use of a metal-organic cage built from a chiral formylpyridine. Fullerenes hosted within the cavity of the cage can be converted into a series of C60 adducts through chemo-, regio- and stereo-selective Diels-Alder reactions with the edges of the cage. The chiral formylpyridine ultimately dictates the stereochemistry of these chiral fullerene adducts without being incorporated into them. Such chiral fullerene adducts may become useful in devices requiring circularly polarized light manipulation.

A chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes.

Rotaxanes can display molecular chirality solely due to the mechanical bond between the axle and encircling macrocycle without the presence of covalent stereogenic units. However, the synthesis of such molecules remains challenging. We have discovered a combination of reaction partners that function as a chiral interlocking auxiliary to both orientate a macrocycle and, effectively, load it onto a new axle. Here we use these substrates to demonstrate the potential of a chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes by producing a range of examples with high enantiopurity (93-99% e.e.), including so-called 'impossible' rotaxanes whose axles lack any functional groups that would allow their direct synthesis by other means. Intriguingly, by varying the order of bond-forming steps, we can effectively choose which end of an axle the macrocycle is loaded onto, enabling the synthesis of both hands of a single target using the same reactions and building blocks.

A Hydrogen-Bonded Ravel Assembled by Anion Coordination.

Anion-coordination-driven assembly (ACDA) is showing increasing power in the construction of anionic supramolecular architectures. Herein, by expanding the anion centers from oxoanion (phosphate or sulfate) to organic tris-carboxylates, an Archimedean solid (truncated tetrahedron) and a highly entangled, double-walled tetrahedron featuring a ravel topology have been assembled with tris-bis(urea) ligands. The results demonstrate the promising ability of tris-carboxylates as new anion coordination centers in constructing novel topologies with increasing complexity and diversity compared to phosphate or sulfate ions on account of the modifiable size and easy functionalization character of these organic anions.

Controlling catalyst activity, chemoselectivity and stereoselectivity with the mechanical bond.

Mechanically interlocked molecules, such as rotaxanes and catenanes, are receiving increased attention as scaffolds for the development of new catalysts, driven by both their increasing accessibility and high-profile examples of the mechanical bond delivering desirable behaviours and properties. In this Review, we survey recent advances in the catalytic applications of mechanically interlocked molecules organized by the effect of the mechanical bond on key catalytic properties, namely, activity, chemoselectivity and stereoselectivity, and focus on how the mechanically bonded structure leads to the observed behaviour. Our aim is to inspire future investigations of mechanically interlocked catalysts, including those outside of the supramolecular community.

"Cannot intubate, cannot oxygenate": A novel 2-operator technique for cannula tracheotomy in an infant animal model-a feasibility study.

BACKGROUND: Evidence regarding optimal management of the "Cannot Intubate, Cannot Oxygenate" (CICO) scenario in infants is scarce. When inserting a transtracheal cannula for front of neck access direct aspiration to confirm intratracheal location is standard practice. This postmortem "infant airway" animal model study describes a novel technique for cannula tracheotomy. AIMS: To compare a novel technique of cannula tracheotomy to an accepted technique to assess success and complication rates. METHODS: Two experienced proceduralists repeatedly performed tracheotomy using an 18-gauge BD InsyteTM cannula (BD, Franklin Lakes, NJ, USA) in 6 postmortem White New Zealand rabbits. Cannulas were attached either directly to a 5ml syringe (Direct Aspiration) or via a 25 cm length minimum volume extension tubing set (TUTA Healthcare Lidcombe, NSW, Australia) (Indirect Aspiration, 2 operator technique). Each technique was attempted a maximum of 12 times per rabbit with an ENT surgeon assessing success and complication rates endoscopically for each attempt. RESULTS: 72 tracheotomy attempts were made in total, 36 for each technique. Initial aspiration through the needle was achieved in 93% (97.2% direct versus 89% indirect). Advancement of the cannula and continued aspiration (success) into the trachea occurred in 67% for direct compared with 64% for indirect aspiration. Direct aspiration was associated with higher rates of lateral (10.3% versus 5.6%) and posterior (19.4% versus 13.9%) wall injury compared with the indirect 2-operator technique. CONCLUSION: Cannula tracheotomy in infant-sized airways is technically difficult and seems frequently associated with tracheal wall injury. The reduced incidence of injury in the indirect group warrants further investigation in preclinical and clinical trials.

2021 Update on airway management from the Anaesthesia Continuing Education Airway Management Special Interest Group.

Airway Management is the key for anaesthetists dealing with patients undergoing diagnostic procedures and surgical interventions. The present coronavirus pandemic underpins even more how important safe airway management is. It also highlights the need to apply stringent precautions to avoid infection and ongoing transmission to patients, anaesthetists and other healthcare workers (HCWs). In light of this extraordinary global situation the aim of this article is to update the reader on the varied aspects of the ever-changing tasks anaesthetists are involved in and highlight the equipment, devices and techniques that have evolved in response to changing technology and unique patient and surgical requirements.

Front-of-neck airway rescue with impalpable anatomy during a simulated cannot intubate, cannot oxygenate scenario: scalpel-finger-cannula versus scalpel-finger-bougie in a sheep model.

BACKGROUND: Front-of-neck airway rescue in a cannot intubate, cannot oxygenate (CICO) scenario with impalpable anatomy is particularly challenging. Several techniques have been described based on a midline vertical neck incision with subsequent finger dissection, followed by either a cannula or scalpel puncture of the now palpated airway. We explored whether the speed of rescue oxygenation differs between these techniques. METHODS: In a high-fidelity simulation of a CICO scenario in anaesthetised Merino sheep with impalpable front-of-neck anatomy, 35 consecutive eligible participants undergoing airway training performed scalpel-finger-cannula and scalpel-finger-bougie in a random order. The primary outcome was time from airway palpation to first oxygen delivery. Data, were analysed with Cox proportional hazards. RESULTS: Scalpel-finger-cannula was associated with shorter time to first oxygen delivery on univariate (hazard ratio [HR]=11.37; 95% confidence interval [CI], 5.14-25.13; P<0.001) and multivariate (HR=8.87; 95% CI, 4.31-18.18; P<0.001) analyses. In the multivariable model, consultant grade was also associated with quicker first oxygen delivery compared with registrar grade (HR=3.28; 95% CI, 1.36-7.95; P=0.008). With scalpel-finger-cannula, successful oxygen delivery within 3 min of CICO declaration and ≤2 attempts was more frequent; 97% vs 63%, P<0.001. In analyses of successful cases only, scalpel-finger-cannula resulted in earlier improvement in arterial oxygen saturations (-25 s; 95% CI, -35 to -15; P<0.001), but a longer time to first capnography reading (+89 s; 95% CI, 69 to 110; P<0.001). No major complications occurred in either arm. CONCLUSIONS: The scalpel-finger-cannula technique was associated with superior oxygen delivery performance during a simulated CICO scenario in sheep with impalpable front-of-neck anatomy.

Synthesis of a Mechanically Planar Chiral Rotaxane Ligand for Enantioselective Catalysis.

Rotaxanes are interlocked molecules in which a molecular ring is trapped on a dumbbell-shaped axle because of its inability to escape over the bulky end groups, resulting in a so-called mechanical bond. Interlocked molecules have mainly been studied as components of molecular machines, but the crowded, flexible environment created by threading one molecule through another has also been explored in catalysis and sensing. However, so far, the applications of one of the most intriguing properties of interlocked molecules, their ability to display stereogenic units that do not rely on the stereochemistry of their covalent subunits, termed "mechanical chirality," have yet to be properly explored, and prototypical demonstration of the applications of mechanically chiral rotaxanes remain scarce. Here, we describe a mechanically planar chiral rotaxane-based Au complex that mediates a cyclopropanation reaction with stereoselectivities that are comparable with the best conventional covalent catalyst reported for this reaction.

Simplicity in the Design, Operation, and Applications of Mechanically Interlocked Molecular Machines.

Mechanically interlocked molecules are perhaps best known as components of molecular machines, a view further reinforced by the Nobel Prize in 2016 to Stoddart and Sauvage. Despite amazing progress since these pioneers of the field reported the first examples of molecular shuttles, genuine applications of interlocked molecular machines remain elusive, and many barriers remain to be overcome before such molecular devices make the transition from impressive prototypes on the laboratory bench to useful products. Here, we discuss simplicity as a design principle that could be applied in the development of the next generation of molecular machines with a view to moving toward real-world applications of these intriguing systems in the longer term.

Intakes and Food Sources of Dietary Fibre and Their Associations with Measures of Body Composition and Inflammation in UK Adults: Cross-Sectional Analysis of the Airwave Health Monitoring Study.

The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007-2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.

Effect of Apneic Oxygenation on Tracheal Oxygen Levels, Tracheal Pressure, and Carbon Dioxide Accumulation: A Randomized, Controlled Trial of Buccal Oxygen Administration.

BACKGROUND: Apneic oxygenation via the oral route using a buccal device extends the safe apnea time in most but not all obese patients. Apneic oxygenation techniques are most effective when tracheal oxygen concentrations are maintained >90%. It remains unclear whether buccal oxygen administration consistently achieves this goal and whether significant risks of hypercarbia or barotrauma exist. METHODS: We conducted a randomized trial of buccal or sham oxygenation in healthy, nonobese patients (n = 20), using prolonged laryngoscopy to maintain apnea with a patent airway until arterial oxygen saturation (SpO2) dropped <95% or 750 seconds elapsed. Tracheal oxygen concentration, tracheal pressure, and transcutaneous carbon dioxide (CO2) were measured throughout. The primary outcome was maintenance of a tracheal oxygen concentration >90% during apnea. RESULTS: Buccal patients were more likely to achieve the primary outcome (P < .0001), had higher tracheal oxygen concentrations throughout apnea (mean difference, 65.9%; 95% confidence interval [CI], 62.6%-69.3%; P < .0001), and had a prolonged median (interquartile range) apnea time with SpO2 >94%; 750 seconds (750-750 seconds) vs 447 seconds (405-525 seconds); P < .001. One patient desaturated to SpO2 <95% despite 100% tracheal oxygen. Mean tracheal pressures were low in the buccal (0.21 cm·H2O; SD = 0.39) and sham (0.56 cm·H2O; SD = 1.25) arms; mean difference, -0.35 cm·H2O; 95% CI, 1.22-0.53; P = .41. CO2 accumulation during early apnea before any study end points were reached was linear and marginally faster in the buccal arm (3.16 vs 2.82 mm Hg/min; mean difference, 0.34; 95% CI, 0.30-0.38; P < .001). Prolonged apnea in the buccal arm revealed nonlinear CO2 accumulation that declined over time and averaged 2.22 mm Hg/min (95% CI, 2.21-2.23). CONCLUSIONS: Buccal oxygen administration reliably maintains high tracheal oxygen concentrations, but early arterial desaturation can still occur through mechanisms other than device failure. Whereas the risk of hypercarbia is similar to that observed with other approaches, the risk of barotrauma is negligible. Continuous measurement of advanced physiological parameters is feasible in an apneic oxygenation trial and can assist with device evaluation.

SciPhon: a data analysis software for nuclear resonant inelastic X-ray scattering with applications to Fe, Kr, Sn, Eu and Dy.

The synchrotron radiation technique of nuclear resonant inelastic X-ray scattering (NRIXS), also known as nuclear resonance vibrational spectroscopy or nuclear inelastic scattering, provides a wealth of information on the vibrational properties of solids. It has found applications in studies of lattice dynamics and elasticity, superconductivity, heme biochemistry, seismology, isotope geochemistry and many other fields. It involves probing the vibrational modes of solids by using the nuclear resonance of Mössbauer isotopes such as 57Fe, 83Kr, 119Sn, 151Eu and 161Dy. After data reduction, it provides the partial phonon density of states of the Mössbauer isotope that is investigated, as well as many other derived quantities such as the mean force constant of the chemical bonds and the Debye velocity. The data reduction is, however, not straightforward and involves removal of the elastic peak, normalization and Fourier-Log transformation. Furthermore, some of the quantities derived are highly sensitive to details in the baseline correction. A software package and several novel procedures to streamline and hopefully improve the reduction of the NRIXS data generated at sector 3ID of the Advanced Photon Source have been developed. The graphical user interface software is named SciPhon and runs as a Mathematica package. It is easily portable to other platforms and can be easily adapted for reducing data generated at other beamlines. Several tests and comparisons are presented that demonstrate the usefulness of this software, whose results have already been used in several publications. Here, the SciPhon software is used to reduce Kr, Sn, Eu and Dy NRIXS data, and potential implications for interpreting natural isotopic variations in those systems are discussed.