Large Ring Research Articles

Effects of AAEMs on the char heterogeneous structure evolution during Zhundong coal pyrolysis: Insights from micro-Raman spectroscopy

The effects of alkali and alkaline earth metallic species (AAEMs) on the heterogeneous evolution of coal/char structure during pyrolysis are rarely investigated. In this study, micro-Raman mapping technology was developed to characterize the effects of AAEMs on the distribution and heterogeneous evolution of the chemical structure of coal/char particles on micro-scale during pyrolysis. The pyrolysis chars from raw coal, leached coal and loaded coal samples were prepared by using a thermogravimetric analyzer, and more than 300 Raman spectra for each sample were analyzed by micro-Raman mapping technology. The results indicate that the water-soluble AAEMs inhibit the release of volatiles during the whole pyrolysis process. The ion-exchangeable AAEMs promote the release of volatiles at the early stage of pyrolysis and then inhibit the release. For integral char structure evolution, water-soluble and ion-exchangeable AAEMs enhance the average relative amount of small aromatic rings obviously at the devolatilization stage and aromatization polymerization stage, respectively. Besides, both water-soluble and ion-exchangeable AAEMs firstly decrease the average relative amount of active structures obviously and then slightly. For heterogeneous evolution, at the devolatilization stage, the water-soluble AAEMs promote the crack of polyolefin and substitutional groups from active components, and the transformation of these species to small aromatic rings. Meanwhile, water-soluble AAEMs promote the breakdown of the cross-linked structures of the large aromatic ring system from inert components and decrease the heterogeneity of the chemical structure of char particles obviously. Besides, the ion-exchangeable AAEMs promote the breakdown of chemical bonds between aromatic rings and the release of the active components. At the aromatization polymerization stage, the ion-exchangeable AAEMs inhibit the condensation of small aromatic rings and increase the heterogeneity of the chemical structure of char particles. In the later stage of pyrolysis, char chemical structure tends to be stable and AAEMs have little effect on the chemical structure of char particles.

Performance study of self‐excited oscillatory cyclone drainage tool to improve the efficiency of natural gas well drainage and gas recovery

AbstractThe accumulation of fluid in the wellbore of a natural gas well can seriously affect the production of the well and can even lead to the well flooding and stopping production. The conventional cyclone tool has low kinetic energy, serious energy loss and short effective distance of spiral flow in the process of gas well drainage and gas recovery, thus affecting the efficiency of gas well drainage and gas recovery. In response to the above problems, this paper proposes a new cyclonic drainage solution combining self‐excited oscillating pulse jet and cyclonic flow. The liquid‐carrying air flow through the oscillating chamber forms a large vortex ring and the flow pattern squeezes the central air flow inwards, allowing the return vortex at the wall to develop effectively, increasing the return vortex velocity and increasing the velocity at the centre of the squeezed pulsating flow. In this paper, based on theoretical analysis and experimental research, the numerical simulation results are compared with the various drainage performance of conventional cyclone tools. The results show that the pressure drop and critical fluid‐carrying velocity of the cyclone section are significantly reduced, and the average tangential velocity of the cyclone section and the effective action distance of the cyclone tool are significantly increased, indicating that the new cyclone tool can improve the fluid‐carrying capacity of gas wells by changing the flow pattern of the gas–liquid medium without increasing energy consumption.

Syntheses and Catalytic Behavior of Dendritic Macrocyclic Schiff‐Base Nickel (II) Complexes in Ethylene Oligomerization

AbstractThe functionalized dendrimers play an important role in catalytic application. A dendritic Schiff base macrocyclic compound was designed and synthesized with the 1.0 generation dendrimer polyamidoamine (1.0G PAMAM) and terephthalaldehyde for ethylene oligomerization. The role of solvent in the synthesized process of dendritic macrocyclic Schiff base ligand was studied. Surprisingly, intermolecular or intramolecular cyclization occurred and formed bicyclic Schiff base ligand (Ligand 1) and polycyclic Schiff base ligand (Ligand 2). And their corresponding nickel complexes (Catalyst 1 and Catalyst 2) were also synthesized with NiCl2(DME) as material to be used for ethylene oligomerization. The effects of the reaction parameters and the chemical structure of the ligand on the catalytic behavior were investigated with methyl‐aluminoxane (MAO) as cocatalyst, and Catalyst 1 and Catalyst 2 displayed the high catalytic activity and the high selectivity for low‐carbon olefin in ethylene oligomerization. Catalyst 2 based on Ligand 2 had a higher catalytic activity of 9.12×104 g (mol Ni h)−1 in ethylene oligomerization because of large dendritic ring in the ligand for ethylene diffusion and mass transfer. Moreover, two synthesized nickel complexes based on dendritic macrocyclic Schiff base ligand had a higher catalytic activity compared with the corresponding dendritic salicylaldehydeimine nickel (II) catalyst.

Reconfigurable Millimeter-Wave Tri-Band Antenna Based on VO2-Films-Embedded Co-Aperture Metasurface Structures

A novel reconfigurable millimeter-wave tri-band antenna using co-aperture metasurface structures embedded with electrically controlling vanadium dioxide (VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) films is proposed. A co-aperture metasurface structure is designed by loading a large square ring surrounded with eight small square patches in the same aperture. By embedding the VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film into the large ring, two lower frequencies of 22 and 28 GHz can be excited and switched when the film operates in metallic and insulating states respectively. Meanwhile, an extra higher-mode resonance at 40 GHz is produced by the small patches. Benefit from the reasonable co-aperture layout, the three frequency bands exhibit good independent tunability. Furthermore, the tri-band metasurface structure is used as radiation element to construct a reconfigurable antenna. To realize good feeding coupling at three bands with large frequency ratio for the antenna, a new kind of combined slot is proposed and etched on the transverse surface of the feeding waveguide. The combined slot contains a loop slot, a dumbbell-shaped slot and two U-shaped slots, corresponding to low, medium and high frequencies respectively. In addition, a simple coplanar DC bias circuit with little effect on radiation is designed. As results, when the VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film is in insulating state, the antenna can simultaneously cover two bands of 27.7-29.8 GHz and 38.8-40 GHz with the maximum gain of about 8.7 dBi and 9.5 dBi respectively; when the film is activated to metallic state, it can also work in two bands of 21.1-21.6 GHz and 38.6-40 GHz with the maximum gain of about 7.2 dBi and 9.3 dBi. Compared with other reported VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -based antennas, the proposed antenna can work in three different bands with adjustable frequency ratio and superior radiation performance.

Preliminary evaluation of penile papule dermatoses with reflectance confocal microscopy in children.

Owing to their similar appearance, lichen striatus (LS), lichen nitidus (LN), juvenile xanthogranuloma (JXG), and molluscum contagiosum (MC) on the penis often lead to misdiagnosis and missed diagnosis, especially in children. In vivo evaluation of penile dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. We recruited 12 patients with LS, nine with LN, seven with JXG, and nine with MC and evaluated the characteristics and distinguishing features of the four kinds of papule dermatoses on the penis using RCM. The four dermatoses all had unique RCM features. LS generally showed focally destroyed dermal papillary rings, with numerous mononuclear cell clusters aggregated inside the papillary rings, and highly refractive clumps were observed. For LN, the dermal papillary rings were completely destroyed and arranged in a solitary, enlarged, cavity-like structure, in which round cells, particulate matter structures, and plump cellular structures were aggregated; the adjacent skin was completely normal. In JXG, the dermal papillary rings were significantly dilated, and the superficial dermis was filled with different-sized large bright ring cells; smaller, refractive, roundish structures; and particulate matter. For MC, the normal structures completely disappeared; the lesions were arranged in a crater-shaped structure; and a mass-like substance formed by the aggregation of multiple, uniform, roundish structures was observed within the crater. RCM allows for real-time visualization of major key diagnostic and distinguishing features of four papule dermatoses, LS, LN, JXG, and MC, on the penis in children.

Experimental study on the impulsively started motion of a close-to-neutral buoyancy freely decelerating sphere

An experimental study is presented that addresses the problem of a freely decelerating sphere in a still water tank. The diameter of the sphere was 0.04 m. Three different solid-to-fluid density ratios were considered: 0.78, 0.88, and 0.94. The submerged sphere was impulsively started upon being rammed by an actuator-mass system. Six initial velocities were considered: 0.91, 2.03, 2.54, 2.94, 3.29, and 3.78 m/s. The Reynolds number of the initial velocities based on the sphere diameter was 3.6 × 104, 8.1 × 104, 1.01 × 105, 1.17 × 105, 1.31 × 105, and 1.51 × 105 (subcritical). It was observed that both sphere dynamics and associated flow topology (identified via an optical system and a particle image velocimetry system, respectively) differed significantly from the case of an accelerating sphere. In the present case, a large vortex ring structure (both torus diameters of the order of the sphere's diameter) formed and attached to the sphere surface. This vortex ring followed the sphere motion all the way down the falling trajectory. From the data reduction standpoint, it was found that a suitably defined dimensionless acceleration parameter allowed for collapsing the kinematics variables of the sphere trajectory, namely, position, velocity, and acceleration, into a single ordinary differential equation.

Study of the structure of MgSiO3 system under compression by using ring statistics and voronoi analysis

The structural change of MgSiO3 liquid under compression is still one of the most interesting challenges. In this paper, we perform the molecular dynamics simulation to study the structural change of MgSiO3 liquid from 0 to 200 GPa. Ring statistics are analyzed to clarify the intermediate-range order, to explain why the second peak of Si–Si PRDFs splits into 2 subpeaks at 200 GPa, and to show the heterogeneity of MgSiO3. Large rings which form at high pressures would capture the oxygen atoms. Oxygen atoms which have negative charge attract Mg2+ ions, creating magnesium-rich regions. Besides, the Voronoi and Q n distribution changes on the ring with pressure are clarified to give more information about the rings.

Alignment & stability challenges for FCC-ee

In order to achieve its ultra-low vertical emittance (1 pm) and high luminosity (of up to 230 times 10^{34}text{ cm}^{-2}text{ s}^{-1} per collision point), the e+e− Future Circular Collider (FCC-ee) requires a well-informed alignment strategy, powerful correction methods, and good understanding of the impact of vibrations. The large ring size, high natural chromaticity, small beta ^{*}, and the low coupling ratio make the FCC-ee design susceptible to misalignment and field errors, which if not properly addressed, threaten to increase the horizontal and vertical emittances and adversely affect the luminosity. Tight alignment tolerances around the 100 km ring would be a major cost driver and therefore alignment and stability need to be carefully studied. In this paper we present a status update, in which we apply analytical estimate methods, verified with simulation data, to determine the influence of the alignment of specific magnet types with the result informing the relative alignment tolerances. This is followed by simulations of a correction strategy that includes a large set of magnet misalignments and field errors. Finally, we also consider the tolerances on vibrations of quadrupoles through evaluating three cases: coherent vibration due to external seismic motion, vibrations resonant with the betatron frequency, and non-resonant, incoherent vibration.

Atomic Structures and Glass-Forming Ability of Pd-Based Bulk Metallic Glasses

To understand the relation of the glass-forming ability (GFA) to the atomic configurations of Pd42.5Ni7.5Cu30P20 (PNCP) metallic glass having the best GFA at present, the local structures were investigated by combining data obtained anomalous x-ray scattering, x-ray and neutron diffraction and applying reverse Monte Carlo modeling. By comparing the results of PNCP with Pd40Ni40P20 and Pd40Cu40P20 having a slightly and much worse GFAs, respectively, characteristic features were observed in the hyper-ordered atomic structures around the secondary metals of Ni and Cu, such as the concentration inhomogeneity, the fraction of pure and slightly distorted icosahedra, and the existence of large persistent homology rings. The structural heterogeneity for the excellent GFA of PNCP would be considered by an incompatible mixture of covalent-like Pd-P configurations and icosahedral clusters around the secondary metals.

The relationship between the adsorption configuration and fermi energy levels in the conversion process of Li2S6/Li2S8 on the ZrO2 surface

The transition metal oxide ZrO2 can clearly adsorb large lithium-sulfur rings (Li2S6 and Li2S8) and exhibits good conversion performance. To study the adsorption strengths of Li2S6/8, the configuration evolution and adsorption energies of Li2S6 and Li2S8 on the ZrO2 surfaces of tetragonal (t-ZrO2), cubic (c-ZrO2), and monoclinic (m-ZrO2) are calculated by a first-principles method. The results show that the Fermi level controls the adsorption and conversion strength. The relationship between the Fermi level in the partial densities of state (PDOS) and the adsorption strength of the large lithium-sulfur ring is studied for the three surfaces formed by the different crystal structures of ZrO2. The crystal structure of ZrO2 can affect the Fermi energy level of S and Zr when Li2S6/Li2S8 adsorbs on the ZrO2 surface. A change from p-type catalysis for Li2S6 and Li2S8 on the t-ZrO2 surface to the N-type catalysis model on the m-ZrO2 surface is established based on the change in the Fermi level. The c-ZrO2 conversion surface, the Fermi energy of which level is located between the valence and conduction bands, has the moderate adsorption energy. Double Li atoms adsorption on the dimer row of O atoms bridge not only leads to ring opening but also breaks the long chain to degrade Li2S6/Li2S8.

The Pretension Design of Cable Mesh considering the Large Deformation of Ring Truss

The conventional pretension design of cable mesh usually takes the ring truss as a rigid body or assumes small deformation. This method needs to be more accurate in designing super large aperture antennas. A cable mesh design method considering the large deformation of the ring truss is proposed in this paper based on the flexible multibody dynamics (FMD) and the force density method (FDM). With this method, the significant range deviation of the boundary points’ position of the ring truss under the tension of the external area of the cable mesh after the completion of the pretension design can be predicted with high accuracy. After the ring truss and cable mesh surface are assembled stably, there is only a minimal deviation between the actual mesh surface and the theoretical mesh surface of the antenna, and there is only a minimal deviation between the genuine mesh pretension and the design pretension. The above calculation method is verified by numerical simulation, and the simulation results show that the technique can be applied to the mesh pretension design of a super large aperture ring deployable antenna.

Direct inhibition of bisphenols on human and rat 11β-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis

Bisphenols (BPs) as endocrine-disrupting compounds have drawn attention to their health hazards. Whether a BP interferes with glucocorticoid metabolism remains unclear. 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) is a key glucocorticoid-metabolizing enzyme that controls fetal glucocorticoid levels across the placental barrier and mineralocorticoid receptor specificity in the kidney. In this study, 11 BPs were tested to inhibit human placental and rat renal 11β-HSD2 and were analyzed for inhibitory potency, mode action, and docking parameters. BPs had inhibitory potency against human 11β-HSD2: BPFL>BPAP>BPZ>BPB>BPC>BPAF>BPA>TDP and the IC10 values were 0.21, 0.55, 1.04, 2.04, 2.43, 2.57, 14.43, and 22.18 μM, respectively. All BPs are mixed inhibitors except BPAP, which is a competitive inhibitor for human 11β-HSD2. Some BPs also inhibited rat renal 11β-HSD2, with BPB (IC50, 27.74 ± 0.95) > BPZ (42.14 ± 0.59) > BPAF (54.87 ± 1.73) > BPA (77.32 ± 1.20) > other BPs (about 100 μM). Docking analysis showed that all BPs bound to the steroid-binding site, interacting with the catalytic residue Tyr232 of both enzymes and the most potent human 11β-HSD2 inhibitor BPFL acts possibly due to its large fluorene ring that has hydrophobic interaction with residues Glu172 and Val270 and π-stacking interaction with catalytic residue Tyr232. The increase in the size of substituted alkanes and halogenated groups in the methane moiety of the bridge of BPs increases its inhibitory potency. Regressions of the lowest binding energy with inhibition constant indicated that there was an inverse regression. These results indicated that BPs significantly inhibited human and rat 11β-HSD2 activity and that there were species-dependent differences.

Scattered polarized radiation of extrasolar circumplanetary rings

Aims. We have investigated the impact of circumplanetary rings consisting of spherical micrometer-sized particles on the net scattered light polarization of extrasolar gas giants. Methods. Using the three-dimensional Monte Carlo radiative transfer code POLARIS, we studied the impact of the macroscopic parameters that define the ring, such as its radius and inclination, and the chemical composition of the ring particles on the net scattered polarization. For the spherical ring particles, we applied the Mie scattering theory. We studied the flux and polarization of the scattered stellar radiation as a function of planetary phase angle and wavelength from the optical to the near-infrared. Results. For the chosen grain size distribution, the dust particles in the ring show strong forward scattering at the considered wavelengths. Thus, the reflected flux of the planet dominates the total reflected and polarized flux at small phase angles. However, the scattered and polarized flux of the ring increase at large phase angles and exceeds the total reflected planetary flux. For large rings that contain silicate particles, the total reflected flux is dominated by the radiation scattered by the dust in the ring at all phase angles. As a result, the orientation of polarization is parallel to the scattering plane at small phase angles. In contrast, for a ring that contains water ice particles, the orientation of polarization is parallel to the scattering plane at large phase angles. Depending on the ring inclination and orientation, the total reflected and polarized flux show a specific distribution as well. Large particles show a strong polarization at large phase angles compared to smaller particles. For a Jupiter-like atmosphere that contains methane and aerosols, methane absorption features are missing in the spectrum of a ringed planet. Conclusions. Scattering of the stellar radiation by dust in circumplanetary rings of extrasolar planets results in unique features in the phase-angle- and wavelength-dependent reflected and polarized net flux. Thus, exoplanet polarimetry provides the means to study not only the planetary atmosphere and surface, but also to identify the existence and constrain the properties of exoplanetary rings.

Toward a diffraction limited light source

This paper introduces a storage ring lattice design for synchrotron radiation sources which fulfills all the required features for the realization of a diffraction limited light source. Insertion devices half gaps of 2.5 mm are assumed and enabled by the design of dedicated straight sections. The use of long straight sections is possible for such a lattice and led to the definition of a set of transparency conditions used to minimize the effect of such insertions for on- and off- energy beam dynamics. The design proposed enables an extremely long Touschek lifetime and beam accumulation. A real case study will be shown for large circumference storage ring upgrade lattices.17 MoreReceived 17 October 2022Accepted 17 January 2023DOI:https://doi.org/10.1103/PhysRevAccelBeams.26.021601Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasBeam dynamicsBeam trackingCollimationHigher order beam dynamicsLattices in beam opticsSingle-particle dynamicsAccelerators & Beams

Interaction of dynamic error signals in saccade adaptation.

Motor adaptation maintains movement accuracy. To evaluate movement accuracy, motor adaptation relies on an error signal, generated by the movement target, while suppressing error signals from irrelevant objects in the vicinity. Previous work used static testing environments, where all information required to evaluate movement accuracy was available simultaneously. Using saccadic eye movements as a model for motor adaptation, we tested how movement accuracy is maintained in dynamic environments, where the availability of conflicting error signals varied over time. Participants made a vertical saccade toward a target (either a small square or a large ring). Upon saccade detection, two candidate stimuli were shown left and right of the target, and participants were instructed to discriminate a feature on one of the candidates. Critically, candidate stimuli were presented sequentially, and saccade adaptation, thus, had to resolve a conflict between a task-relevant and a task-irrelevant error signal that were separated in space and time. We found that the saccade target influenced several aspects of oculomotor learning. In presence of a small target, saccade adaptation evaluated movement accuracy based on the first available error signal after the saccade, irrespective of its task relevance. However, a large target not only allowed for greater flexibility when evaluating movement accuracy, but it also promoted a stronger contribution of strategic behavior when compensating inaccurate saccades. Our results demonstrate how motor adaptation maintains movement accuracy in dynamic environments, and how properties of the visual environment modulate the relative contribution of different learning processes.NEW & NOTEWORTHY Motor adaptation is typically studied in static environments, where all information that is required to evaluate movement accuracy is available simultaneously. Here, using saccadic eye movements as a model, we studied motor adaptation in a dynamic environment, where the availability of conflicting information about movement accuracy varied over time. We demonstrate that properties of the visual environment determine how dynamic movement errors are corrected.

Sensing local field potentials with a directional and scalable depth electrode array

Objective. A variety of electrophysiology tools are available to the neurosurgeon for diagnosis, functional therapy, and neural prosthetics. However, no tool can currently address these three critical needs: (a) access to all cortical regions in a minimally invasive manner; (b) recordings with microscale, mesoscale, and macroscale resolutions simultaneously; and (c) access to spatially distant multiple brain regions that constitute distributed cognitive networks. Approach. We modeled, designed, and demonstrated a novel device for recording local field potentials (LFPs) with the form factor of a stereo-electroencephalographic electrode and combined with radially distributed microelectrodes. Main results. Electro-quasistatic models demonstrate that the lead body amplifies and shields LFP sources based on direction, enabling di rectional sensitivity and sc alability, referred to as the directional and scalable (DISC) array. In vivo, DISC demonstrated significantly improved signal-to-noise ratio, directional sensitivity, and decoding accuracy from rat barrel cortex recordings during whisker stimulation. Critical for future translation, DISC demonstrated a higher signal to noise ratio (SNR) than virtual ring electrodes and a noise floor approaching that of large ring electrodes in an unshielded environment after common average referencing. DISC also revealed independent, stereoscopic current source density measures whose direction was verified after histology. Significance. Directional sensitivity of LFPs may significantly improve brain–computer interfaces and many diagnostic procedures, including epilepsy foci detection and deep brain targeting.

The CM class number one problem for curves of genus 2

Gauss’s class number one problem, solved by Heegner, Baker, and Stark, asked for all imaginary quadratic fields for which the ideal class group is trivial. An application of this solution gives all elliptic curves that can be defined over the rationals and have a large endomorphism ring (CM). Analogously, to get all CM curves of genus two defined over the smallest number fields, we need to find all quartic CM fields for which the CM class group (a quotient of the ideal class group) is trivial. We solve this CM class number one problem. We prove that the list given in Bouyer–Streng [LMS J Comput Math 18(1):507–538, 2015, Tables 1a, 1b, 2b, and 2c] of maximal CM curves of genus two defined over the reflex field is complete. We also prove that there are exactly 21 simple CM curves of genus two over $$\mathbb {C}$$ that can be defined over $$\mathbb {Q}$$ .

Olefin Metathesis under Spatial Confinement and Continuous Flow: Investigation of Isomeric Side Reactions with a Grubbs–Hoveyda Type Catalyst

AbstractA 2nd‐generation Grubbs–Hoveyda type catalyst was immobilized inside mesoporous silica and used in the ring‐closing metathesis (RCM) of an α,ω‐diene to a large macro(mono)cycle. The goal was to investigate the relationship between substrate concentration, reaction time, and overall experiment time on the rate of isomerization under spatial (mesopore space) confinement with continuous‐flow microreactors. RCM reactions are commonly monitored by 1H NMR analysis, however, elucidation of reaction mixtures yielding large rings with a difference of only a single carbon atom remains difficult, because NMR signals are sometimes indistinguishable. In this work, an analytical platform with on‐line separation and detection of UV‐active substrate as well as (side) products by high‐performance liquid chromatography and a UV/Vis‐diode array detector (DAD) plus mass spectrometry served as enabling technology to quantify yield and selectivity under the respective reaction conditions. Using this setup, competitive reaction equilibria and isomerization reactions, in particular, could be resolved. Identification and quantification of relevant compounds of the reaction scheme under spatial confinement became possible despite chemical similarity. Kinetic data revealed that isomerization increases with higher substrate concentrations (up to 250 mM) and longer reaction times (from 1.2 to 18.6 min), but shows a distinct decline for prolonged overall experiment times (up to ∼250 min).

Balancing ring and stopper group size to control the stability of doubly threaded [3]rotaxanes.

Synthesizing doubly threaded [3]rotaxanes requires the use of larger rings than more traditional singly threaded [2]rotaxanes. A key challenge in accessing stable doubly threaded [3]rotaxanes with large rings is finding the right combination of ring to stopper size. In this study, a series of doubly threaded [3]rotaxanes derived from five different sized macrocycles in the size range of 40-48 atoms and two different stopper groups, which contain 1 or 2 tris(p-t-butylbiphenyl)methyl moieties, were prepared and their kinetic stability examined. These interlocked compounds were synthesized using a metal-templated approach and fully characterized utilizing a combination of mass spectrometry, NMR spectroscopy, and size-exclusion chromatography techniques. The effect of ring size on the stability of the doubly threaded [3]rotaxane was investigated via kinetic stability tests monitored using 1H-NMR spectroscopy. By tightening the macrocycle systematically every 2 atoms from 48 to 40 atoms, a wide range of doubly threaded interlocked molecules could be accessed in which the rate of room temperature slippage of the macrocycle from the dumbbells could be tuned. Using the larger stopper group with a 48-atom ring results in no observable rotaxane, 46-44 atom macrocycles result in metastable rotaxane species with a slippage half-life of ∼5 weeks and ∼9 weeks, respectively, while macrocycles of 42 atoms or smaller yield a stable rotaxane. The smaller sized stopper is not able to fully stabilize any of the [3]rotaxane structures but metastable [3]rotaxanes are obtained with slippage half-lives of 25 ± 2 hours and 13 ± 1 days using macrocycles with 42 or 40 atoms, respectively. These results highlight the dramatic effect that relatively small ring size changes can have on the structure of doubly threaded [3]rotaxanes and lay the synthetic groundwork for a range of higher order doubly threaded interlocked architectures.

Structure-activity relationship of berberine and G4 DNA reveals aromaticity’s effect on binding affinity

Secondary nucleic acid structures, such as the Guanine Quadruplex (G4), are known to contribute to gene regulation throughout the genome. In cancer cells, stabilizing such structures could prove to be integral to inhibiting cancer cell proliferation. Berberine is a natural quaternary alkaloid with a number of medicinal properties, including antimicrobial and anticancer effects. Previous studies have shown that berberine can stabilize the G4 through π-π interactions, by increasing the release of free energy. In this study, we test the effectiveness of ligand aromaticity (cyclic, planar molecules) on the free energy of binding with the G4. Based on previous studies, we hypothesized that large aromatic rings incorporated in berberine molecules would act as highly stabilizing ligands that would generate the greatest binding affinity with the G4 through π interactions with guanine endplates and K+ ions. To explore the structure-activity relationship for berberine-based ligands, we developed an in silico library of 800+ ligands. Through molecular docking, we predicted the free energy release of each ligand’s interaction with the G4 complex. From our research, we found that berberine analogs with aromatic R groups, which allow for high degrees of aromaticity and flexibility, have a significant positive impact on binding strength between berberine analogs and G4 complexes through π-π interactions with endplates and grooves, indicating that these ligands can more effectively bind to and stabilize the G4’s activity. The authors envision that this research may aid the development of drugs that target the G4 to inhibit cancer cell proliferation, ultimately furthering cancer therapeutics research.