A pyridine-N-oxide catenane for cation recognition.

The rapid preparation of a pyridine-N-oxide containing [2]catenane is described. The [2]catenane was characterized by NMR spectroscopy, mass spectrometry and X-ray single crystal structure determination. 1H NMR titration experiments reveal the [2]catenane may be reversibly protonated, as well as an ability to bind lithium cations more strongly than sodium cations.

Rapid synthesis of hydrogen bond templated handcuff rotaxanes.

The rapid synthesis of hydrogen bond templated handcuff rotaxanes is described. The isolated rotaxanes were characterized by NMR and IR spectroscopies and high resolution mass spectrometry. This report represents a rare demonstration of preparing (2)handcuff [2]rotaxanes by covalently linking separate axles threaded through the rings of a bis-macrocycle by use of the copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction.

Brief High-Velocity Motor Skill Training Increases Step Frequency and Improves Length/Frequency Coordination in Slow Walkers With Chronic Motor-Incomplete Spinal Cord Injury.

OBJECTIVE: To quantify spatiotemporal coordination during overground walking among persons with motor-incomplete spinal cord injury (PwMISCI) by calculating the step length (SL)/step frequency (SF) ratio (ie, the Walk Ratio [WR]) and to examine the effects of motor skill training (MST) on the relationship between changes in these parameters and walking speed (WS). DESIGN: Between-day exploratory analysis. SETTING: Research laboratory in a rehabilitation hospital PARTICIPANTS: PwMISCI (N=26). INTERVENTIONS: 3-day high-velocity MST. MAIN OUTCOME MEASURES: Overground WS, SL, SF, and WR measured during the 10-Meter Walk Test. RESULTS: Among the full sample, MST was associated with increases in WS, SL, SF, and a decrease in the WR. Relative change in WS and SF was higher among slow (ΔWS=↑46%, ΔSF=↑28%) vs fast (ΔWS=↑16%, ΔSF=↑8%) walkers. Change in the WR differed between groups (slow: ΔWR=↓10%; fast: ΔWR=0%). Twenty-six percent of the variability observed in ΔWR among slow walkers could be explained by ΔSF, while ΔSL did not contribute to ΔWR. Among fast walkers, ΔSL accounted for more than twice the observed ΔWR (43%) compared to ΔSF (15%). CONCLUSIONS: On the whole, WR values among PwMISCI are higher than previous reports in other neurologic populations; however, values among fast walkers were comparable to noninjured adults. Slow walkers demonstrated greater variability in the WR, with higher values associated with slower WS. Following MST, increases in WS coincided with a decrease in the WR among slow walkers, mediated primarily through an effect on SF. This finding may point to a specific mechanism by which MST facilitates improvements in WS among PwMISCI with greater mobility deficits.

Anion Modulated Expression of Chirality in Hydrogen Bond Templated Mechanically Chiral [2]Rotaxanes.

The syntheses of two novel mechanically chiral rotaxanes containing urea and squaramide motifs (in yields of 33 % and 22 %, respectively) are presented. 1 H NMR spectroscopic titrations reveal shuttling of the macrocycle - detectable by modulation of the expression of mechanical chirality in the NMR spectrum - is possible through the addition of achiral chloride anions, a process which is reversed by the addition of sodium cations.

Hydrogen bond templated synthesis of catenanes and rotaxanes from a single isophthalic acid derivative.

Hydrogen bond templated [2]catenanes and [2]rotaxanes have been synthesized using azide precursors derived from a single isophthalic acid derivative precursor. The interlocked molecules were prepared using either stoichiometric or near stoichiometric amounts of macrocycle and CuAAC "click" precursors, with yields of up to 70% for the mechanical bond formation step. Successful preparation of the interlocked structures was confirmed by NMR spectroscopy and mass spectrometry, with detail of co-conformational behaviour being elucidated by a range of 1H NMR spectroscopic experiments.

A Pilot Study of Intensive Locomotor-Related Skill Training and Transcranial Direct Current Stimulation in Chronic Spinal Cord Injury.

BACKGROUND AND PURPOSE: Improved walking function is a priority among persons with motor-incomplete spinal cord injury (PwMISCI). Accessibility and cost limit long-term participation in locomotor training offered in specialized centers. Intensive motor training that facilitates neuroplastic mechanisms that support skill learning and can be implemented in the home/community may be advantageous for promoting long-term restoration of walking function. Additionally, increasing corticospinal drive via transcranial direct current stimulation (tDCS) may enhance training effects. In this pilot study, we investigated whether a moderate-intensity motor skill training (MST) circuit improved walking function in PwMISCI and whether augmenting training with tDCS influenced outcomes. METHODS: Twenty-five adults (chronic, motor-incomplete spinal cord injury) were randomized to a 3-day intervention of a locomotor-related MST circuit and concurrent application of sham tDCS (MST+tDCS sham ) or active tDCS (MST+tDCS). The primary outcome was overground walking speed. Secondary outcomes included walking distance, cadence, stride length, and step symmetry index (SI). RESULTS: Analyses revealed significant effects of the MST circuit on walking speed, walking distance, cadence, and bilateral stride length but no effect on interlimb SI. No significant between-groups differences were observed. Post hoc analyses revealed within-groups change in walking speed (ΔM = 0.13 m/s, SD = 0.13) that app-roached the minimally clinically important difference of 0.15 m/s. DISCUSSION AND CONCLUSIONS: Brief, intensive MST involving locomotor-related activities significantly increased walking speed, walking distance, and spatiotemporal measures in PwMISCI. Significant additive effects of tDCS were not observed; however, participation in only 3 days of MST was associated with changes in walking speed that were comparable to longer locomotor training studies.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A386 ).

An amide hydrogen bond templated [1]rotaxane displaying a peptide motif - demonstrating an expedient route to synthetic mimics of lasso peptides.

The rapid synthesis of an amide hydrogen bond templated [1]rotaxane is reported - demonstrating a potential pathway to synthetic analogues of lasso peptides. The structures of the [1]rotaxane and its unthreaded isomer have been characterized by NMR spectroscopy and modelled using DFT calculations.

Chiral Catenanes and Rotaxanes: Fundamentals and Emerging Applications.

Molecular chirality provides a key challenge in host-guest recognition and other related chemical applications such as asymmetric catalysis. For a molecule to act as an efficient enantioselective receptor, it requires multi-point interactions between host and chiral guest, which may be achieved by an appropriate chiral 3D scaffold. As a consequence of their interlocked structure, catenanes and rotaxanes may present such a 3D scaffold, and can be chiral by inclusion of a classical chiral element and/or as a consequence of the mechanical bond. This Minireview presents illustrative examples of chiral [2]catenanes and [2]rotaxanes, and discusses where these molecules have been used in chemical applications such as chiral host-guest recognition and asymmetric catalysis.

Rapidly accessible "click" rotaxanes utilizing a single amide hydrogen bond templating motif.

The synthesis of hydrogen bond templated rotaxanes using the CuAAC click reaction has been achieved in yields of up to 47%, employing near stoichiometric equivalents of macrocycle and readily prepared azide and alkyne half-axle components. Interlocked structure formation has been confirmed by NMR spectroscopy and mass spectrometry. Density functional theory calculations support 1H NMR spectroscopic analysis that the macrocycle resides over the amide of the axle component, rather than the newly formed triazole, as a result of more favourable hydrogen bond interactions.

The synthesis of a pyridine-N-oxide isophthalamide rotaxane utilizing supplementary amide hydrogen bond interactions.

The synthesis of a pyridine-N-oxide containing rotaxane, not requiring an additional ionic template, has been achieved in 32% yield. Successful rotaxane formation is dependent upon the structure of the isophthalamide macrocycle used, an observation which has been rationalised by a combination of NMR spectroscopy, X-ray crystallography and computational modelling.

The rapid synthesis and dynamic behaviour of an isophthalamide [2]catenane.

A serendipitous [2]catenane has been prepared in three steps from commercially available starting materials. The interlocked topology of the catenane has been confirmed by single crystal X-ray structural determination. The rings of the catenane may rotate relative to one another - a process that may be controlled by varying solvent or temperature.

Progress in the synthesis and exploitation of catenanes since the Millennium.

Catenanes - molecules consisting of interlocked macrocyclic rings - have been prepared by templation strategies for some thirty years. The utilization of Cu(I) cation, aromatic donor-acceptor interactions and hydrogen bonding assisted self-assembly strategies has led to the construction of numerous examples of these aesthetically pleasing species. This review seeks to discuss key developments in the synthesis and functional application of catenanes that have occurred since the Millennium. The much expanded range of metal cation templates; the genesis and growth of anion templation, as well as the use of alternative supramolecular interactions (halogen bonding and radical templation) and thermodynamically controlled reactions to synthesize catenanes are detailed. The class of catenanes that may be described as "molecular machines" are then highlighted and to conclude, attempts to fabricate catenanes onto surfaces and into metal organic frameworks (MOFs) are discussed.

Advances in anion supramolecular chemistry: from recognition to chemical applications.

Since the start of this millennium, remarkable progress in the binding and sensing of anions has been taking place, driven in part by discoveries in the use of hydrogen bonding, as well as the previously under-exploited anion-π interactions and halogen bonding. However, anion supramolecular chemistry has developed substantially beyond anion recognition, and now encompasses a diverse range of disciplines. Dramatic advance has been made in the anion-templated synthesis of macrocycles and interlocked molecular architectures, while the study of transmembrane anion transporters has flourished from almost nothing into a rapidly maturing field of research. The supramolecular chemistry of anions has also found real practical use in a variety of applications such as catalysis, ion extraction, and the use of anions as stimuli for responsive chemical systems.

Lanthanide complexes as chiral probes exploiting circularly polarized luminescence.

Optical probes that provide information about local chirality have been developed based on changes to the circular polarisation of emitted light. Highly emissive complexes of lanthanide ions are ideally suited for CPL spectroscopy and the design criteria for developing such probes are defined, based on a rigorous stereochemical analysis. The perturbation of a dynamically racemic complex may occur either by a change in complex constitution or by non-covalent association. With complexes of enantiopure ligands, perturbation may involve either dynamic helicity inversion or a reversible change in the lanthanide coordination environment.

Isostructural series of nine-coordinate chiral lanthanide complexes based on triazacyclononane.

Nonadentate ligands based on triazacyclononane incorporating pyridyl-2-phosphinate groups form an isostructural series of complexes with Ln ions in the solid state and in solution. The Ln ion is effectively shielded from the solvent environment. Crystal structures reveal a rigid C(3)-symmetric tricapped trigonal-prismatic coordination geometry that is maintained in solution for the methyl and phenylphosphinate series, as shown by multinuclear NMR analysis. Variable-temperature measurements of the field dependence of the water proton relaxivity in gadolinium complexes indicate that these systems exclude solvent from the primary coordination environment and minimize the second sphere of solvation. The electronic relaxation time for the gadolinium methylphosphinate complex has been estimated to be 550 (±150) ps by EPR and NMR methods, compared to values of around 0.30-0.05 ps for the terbium-ytterbium series, deduced by analyzing the field dependence (4.7-16.5 T) of the (31)P NMR longitudinal relaxation times. Values are compared with analogous azacarboxylate ligand complexes, supporting a key role for donor atom polarizability in determining the electronic relaxation. Spectral emission behavior in solution of samarium, europium, terbium, and dysprosium complexes is compared, and the resolved RRR-Λ and SSS-Δ complexes show strong circularly polarized luminescence. The molecular quadratic hyperpolarizability 〈ß(HLS)〉 has been measured in solution using hyper-Raleigh light-scattering methods, for the whole series of lanthanide complexes of one ligand. The values of 〈ß(HLS)〉 reach a maximum around the center of the series and are not simply dependent on the number of f electrons, suggesting a dominant contribution from the octupolar rather than the dipolar term.

Surface-attached sensors for cation and anion recognition.

The development of surface-attached sensors for cationic and anionic guests is of intense current research interest. In addition to the environmental flexibility, robustness and reusability of such devices, surface-confined sensors typically exhibit an amplified response to target analytes owing to preorganization of the receptor. Whereas redox-active cations may be sensed by studying the cyclic voltammetry of host-guest systems containing ion-selective receptors attached to an appropriate electrode, redox-inactive ionic species require the use of electrochemical impedance spectroscopy, with appropriately functionalized electrodes and redox probes. Alternatively, receptors may be constructed that incorporate an electrochemical or optical reporter group within their structure to provide a macroscopic response to the presence of an ionic guest. This critical review seeks to present an up-to-date, although necessarily selective, account of the progress in the field, and provides insights into possible future developments, including the utilization of receptor-nanoparticle conjugates and mechanically interlocked receptors.

Walking and Balance Outcomes Are Improved Following Brief Intensive Locomotor Skill Training but Are Not Augmented by Transcranial Direct Current Stimulation in Persons With Chronic Spinal Cord Injury.

Motor training to improve walking and balance function is a common aspect of rehabilitation following motor-incomplete spinal cord injury (MISCI). Evidence suggests that moderate- to high-intensity exercise facilitates neuroplastic mechanisms that support motor skill acquisition and learning. Furthermore, enhancing corticospinal drive via transcranial direct current stimulation (tDCS) may augment the effects of motor training. In this pilot study, we investigated whether a brief moderate-intensity locomotor-related motor skill training (MST) circuit, with and without tDCS, improved walking and balance outcomes in persons with MISCI. In addition, we examined potential differences between within-day (online) and between-day (offline) effects of MST. Twenty-six adults with chronic MISCI, who had some walking ability, were enrolled in a 5-day double-blind, randomized study with a 3-day intervention period. Participants were assigned to an intensive locomotor MST circuit and concurrent application of either sham tDCS (MST+tDCSsham) or active tDCS (MST+tDCS). The primary outcome was overground walking speed measured during the 10-meter walk test. Secondary outcomes included spatiotemporal gait characteristics (cadence and stride length), peak trailing limb angle (TLA), intralimb coordination (ACC), the Berg Balance Scale (BBS), and the Falls Efficacy Scale-International (FES-I) questionnaire. Analyses revealed a significant effect of the MST circuit, with improvements in walking speed, cadence, bilateral stride length, stronger limb TLA, weaker limb ACC, BBS, and FES-I observed in both the MST+tDCSsham and MST+tDCS groups. No differences in outcomes were observed between groups. Between-day change accounted for a greater percentage of the overall change in walking outcomes. In persons with MISCI, brief intensive MST involving a circuit of ballistic, cyclic locomotor-related skill activities improved walking outcomes, and selected strength and balance outcomes; however, concurrent application of tDCS did not further enhance the effects of MST. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03237234].

A 1,2,3,4,5-pentaphenylferrocene-stoppered rotaxane capable of electrochemical anion recognition.

The chloride anion templated synthesis of an electrochemical anion sensory interlocked host system, prepared by the integration of redox-active 1,2,3,4,5-pentaphenylferrocene stopper groups into the structure of a rotaxane capable of binding anionic guests is described. Extensive (1)H NMR and electrochemical titration investigations were used to probe the anion recognition and sensing properties of the rotaxane, compared to the axle and model system components. A characteristic electrochemical response was observed for chloride binding by the rotaxane, which was attributed to the topologically constrained cavity of the interlocked host molecule.

A ferrocene functionalized rotaxane host system capable of the electrochemical recognition of chloride.

A ferrocene appended rotaxane is prepared by chloride anion templation and ring closing metathesis. Upon removal of the chloride template, the rotaxane is demonstrated to be selective for chloride over more basic oxoanions by (1)H NMR spectroscopy and electrochemistry, in marked contrast to an acyclic analogue--the first example of a solution based redox-active interlocked host system capable of the electrochemical recognition of anions.