Crystal structure of a dicationic PdII dimer containing a 2-[(diisopropylphosphanyl)methyl]quinoline-8-thiolate pincer ligand

A dicationic PdII dimer, bis{2-[(diisopropylphosphanyl)methyl]quinoline-8-thiolato}palladium(II) bis(hexafluoridoantimonate) dichloromethane monosolvate, [Pd2(C32H42N2P2S2)](SbF6)2·CH2Cl2, containing a 2-[(diisopropylphosphanyl)methyl]quinoline-8-thiolate pincer ligand, was isolated and its crystal structure determined. The title compound crystallizes in the orthorhombic space group Pbca. A dimeric structure is formed by bridging coordination of the S atoms. The geometry of the butterfly-shaped Pd2S2 core is bent, with a hinge angle of 108.0 (1)° and a short Pd...Pd distance of 2.8425 (7) Å. These values are the lowest measured compared to ten dicationic dimers with a Pd2S2 core featuring sulfur atoms embedded in a chelating ligand. One of the two hexafluoridoantimonate anions is disordered over two sets of positions with site-occupancy factors of 0.711 (5) and 0.289 (5). The crystal structure is stabilized by many C—H...F and C—H...π interactions, forming a supramolecular network.

Two polymorphs of [Rh(μ-I)(COD)]2

The solid-state structure of di-μ-iodido-bis{[(1,2,5,6-η)-cycloocta-1,4-diene]rhodium(I)}, [Rh2I2(C8H12)2] or [Rh(μ-I)(COD)]2, was determined from two crystals with different morphologies, which were found to correspond to two polymorphs containing Rh dimers with significantly different molecular structures. Both polymorphs are monoclinic and the [Rh(μ-I)(COD)]2 molecules in each case possess C2 v symmetry. However, the core geometry of the butterfly-shaped Rh2I2 core differs substantially. In the C2/c polymorph, the core geometry of [Rh(μ-I)(COD)]2 B is bent, with a hinge angle of 96.13 (8)° and a Rh...Rh distance of 2.9612 (11) Å. The P21/c polymorph features a more planar [Rh(μ-I)(COD)]2 P core geometry, with a hinge angle of 145.69 (9)° and a Rh...Rh distance of 3.7646 (5) Å.

Transformations, Comparisons, and Analysis of Down to Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein Including the UK Variant B.1.1.7

Monitoring and strategic response to variants in SARS-CoV-2 represents a considerable challenge in the current pandemic, as well as potentially future viral outbreaks of similar magnitude. In particular mutations and deletions involving the virion’s prefusion Spike protein has significant potential impact on vaccines and therapeutics that utilize this key structural viral protein in their mitigation strategies. In this study, we have demonstrated how dominant energetic landscape mappings (“glue points”) coupled with sequence alignment information can potentially identify or flag key residue mutations and deletions associated with variants. Surprisingly, we also found excellent homology of stabilizing residue glue points across the lineage of β coronavirus Spike proteins, and we have termed this as “sequence homologous glue points”. In general, these flagged residue mutations and/or deletions are then computationally studied in detail using all-atom biocomputational molecular dynamics over approximately one microsecond in order to ascertain structural and energetic changes in the Spike protein associated variants. Specifically, we examined both a theoretically-based triple mutant and the so called UK or B.1.1.7 variant. For the theoretical triple mutant, we demonstrated through Alanine mutations, which help “unglue” key residue-residue interactions, that these three key stabilizing residues could cause the transition of Down to Up protomer states, where the Up protomer state allows binding of the prefusion Spike protein to hACE2 host cell receptors, whereas the Down state is believed inaccessible. For the B.1.1.7 variant, we demonstrated the critical importance of D614G and N5017 on the structure and binding of the Spike protein associated variant. In particular, we had previously identified D614 as a key glue point in the inter-protomer stabilization of the Spike protein. Other mutations and deletions associated with this variant did not appear to play a pivotal role in structure or binding changes. The mutant D614G is a structure breaking Glycine mutation demonstrating a relatively large hinge angle and highly stable Up conformation in agreement with previous studies. In addition, we demonstrate that the mutation N501Y may significantly increase the Spike protein binding to hACE2 cell receptors through its interaction with Y41 of hACE2 forming a potentially strong hydrophobic residue binding pair. We note that these two key mutations, D614G and N501Y, are also found in the so-called South African (SA; B.1.351) variant of SARS-CoV-2. Future studies along these lines are therefore aimed at mapping glue points to residue mutations and deletions of associated prefusion Spike protein variants in order to help direct and optimize efforts aimed at the mitigation of this deadly virion.

Impact of hinge motion on stent edge restenosis after new generation drug-eluting-stent implantation in RCA

Background Edge restenosis still occurs after stent implantation, even by using new generation drug-eluting stents (DES) considered to have favorable biomechanical properties. Mechanical stress imposed on the stent edge are thought to be aggravated by hinge motion at a point between the stented and unstented segments, inducing chronic local inflammation and neointimal overgrowth. Purpose The aim of this study was to investigate the association between the development of edge restenosis and hinge motion in right coronary artery (RCA) where the excessive vessel movement is commonly observed. Methods Among consecutive 650 lesions in RCA where new generation DESs were implanted between 2009 and 2019, 427 serial lesions with sets of angiographies at baseline and follow-up (6–18 month) were included. In addition to conventional quantitative angiography analysis, hinge angle at stent edges was measured (Fig. 1). All the appropriate data for intravascular imaging were analyzed for both stent edges and reference segments. Results Binary restenosis occurred in 43 lesions, and 39 of them were referred to re-intervention. Fifty five percent of them were related to stent edges (15 at proximal and 9 at distal edges). Classical risk factors including diabetes and hemodialysis were more prevalent in the restenosis group (p<0.05). Hinge angle was statistically larger in edge restenosis group than body restenosis or no restenosis group (17.3° vs 11.6° vs 10.6°, p<0.001, Fig. 2). In per-edge analysis, hinge angle, dissection and residual plaque ratio were the independent predictors for binary restenosis (Table 1) with the optimal cut-off value of hinge angle 11.5°. The coexistence of excessive hinge angle and residual plaque burden had an amplified effect on the angiographic stenotic progression at stent edge (p for interaction <0.001) and the incidents of binary restenosis (16.7% vs 1.7% p<0.01, Figs. 3,4). Conclusion Substantial stress determined by angulation at the stent edge and its interaction with residual plaque can be considered as one of the plausible mechanisms for edge restenosis. For tortuous RCA lesions, it would be important to decide the stent-landing zone for minimizing hinge motion and optimize the future stent design. Funding Acknowledgement Type of funding source: None

Dynamic and asymmetric fluctuations in the microtubule wall captured by high-resolution cryoelectron microscopy

Microtubules are tubular polymers with essential roles in numerous cellular activities. Structures of microtubules have been captured at increasing resolution by cryo-EM. However, dynamic properties of the microtubule are key to its function, and this behavior has proved difficult to characterize at a structural level due to limitations in existing structure determination methods. We developed a high-resolution cryo-EM refinement method that divides an imaged microtubule into its constituent protofilaments, enabling deviations from helicity and other sources of heterogeneity to be quantified and corrected for at the single-subunit level. We demonstrate that this method improves the resolution of microtubule 3D reconstructions and substantially reduces anisotropic blurring artifacts, compared with methods that utilize helical symmetry averaging. Moreover, we identified an unexpected, discrete behavior of the m-loop, which mediates lateral interactions between neighboring protofilaments and acts as a flexible hinge between them. The hinge angle adopts preferred values corresponding to distinct conformations of the m-loop that are incompatible with helical symmetry. These hinge angles fluctuate in a stochastic manner, and perfectly cylindrical microtubule conformations are thus energetically and entropically penalized. The hinge angle can diverge further from helical symmetry at the microtubule seam, generating a subpopulation of highly distorted microtubules. However, the seam-distorted subpopulation disappears in the presence of Taxol, a microtubule stabilizing agent. These observations provide clues into the structural origins of microtubule flexibility and dynamics and highlight the role of structural polymorphism in defining microtubule behavior.

Extreme motion and response statistics for survival of the three-float wave energy converter M4 in intermediate water depth

This paper presents both linear and nonlinear analyses of extreme responses for a multi-body wave energy converter (WEC) in severe sea states. The WEC known as M4 consists of three cylindrical floats with diameters and draft which increase from bow to stern with the larger mid and stern floats having rounded bases so that the overall system has negligible drag effects. The bow and mid float are rigidly connected by a beam and the stern float is connected by a beam to a hinge above the mid float where the rotational relative motion would be damped to absorb power in operational conditions. A range of focussed wave groups representing extreme waves were tested on a scale model without hinge damping, also representing a more general system of interconnected cylindrical floats with multi-mode forcing. Importantly, the analysis reveals a predominantly linear response structure in hinge angle and weakly nonlinear response for the beam bending moment, while effects due to drift forces, expected to be predominantly second order, are not accounted for. There are also complex and violent free-surface effects on the model during the excitation period driven by the main wave group, which generally reduce the overall motion response. Once the main group has moved away, the decaying response in the free-vibration phase decays at a rate very close to that predicted by simple linear radiation damping. Two types of nonlinear harmonic motion are demonstrated. During the free-vibration phase, there are only double and triple frequency Stokes harmonics of the linear motion, captured using a frequency doubling and tripling model. In contrast, during the excitation phase, these harmonics show much more complex behaviour associated with nonlinear fluid loading. Although bound harmonics are visible in the system response, the overall response is remarkably linear until temporary submergence of the central float (‘dunking’) occurs. This provides a strong stabilising effect for angular amplitudes greater than ${\sim}30^{\circ }$ and can be treated as a temporary loss of part of the driving wave as long as submergence continues. With an experimentally and numerically derived response amplitude operator (RAO), we perform a statistical analysis of extreme response for the hinge angle based on wave data at Orkney, well known for its severe wave climate, using the NORA10 wave hindcast. For storms with spectral peak wave periods longer than the RAO peak period, the response is controlled by the steepness of the sea state rather than the wave height. Thus, the system responds very similarly under the most extreme sea states, providing an upper bound for the most probable maximum response, which is reduced significantly in directionally spread waves. The methodology presented here is relevant to other single and multi-body systems including WECs. We also demonstrate a general and potentially important reciprocity result for linear body motion in random seas: the averaged wave history given an extreme system response and the average response history given an extreme wave match in time, with time reversed for one of the signals. This relationship will provide an efficient and robust way of defining a ‘designer wave’, for both experimental testing and computationally intensive computational fluid dynamics (CFD), for a wide range of wave–structure interaction problems.

Structural and Functional Characterization of the Alanine Racemase from Streptomyces coelicolor A3(2)

The conversion of L-alanine (L-Ala) into D-alanine (D-Ala) in bacteria is performed by pyridoxal phosphate-dependent enzymes called alanine racemases. D-Ala is an essential component of the bacterial peptidoglycan and hence required for survival. The Gram-positive bacterium Streptomyces coelicolor has at least one alanine racemase encoded by alr. Here, we describe an alr deletion mutant of S. coelicolor which depends on D-Ala for growth and shows increased sensitivity to the antibiotic D-cycloserine (DCS). The crystal structure of the alanine racemase (Alr) was solved with and without the inhibitors DCS or propionate, at 1.64 Å and 1.51 Å resolution, respectively. The crystal structures revealed that Alr is a homodimer with residues from both monomers contributing to the active site. The dimeric state of the enzyme in solution was confirmed by gel filtration chromatography, with and without L-Ala or D-cycloserine. Specificity of the enzyme was 66 +/− 3 U mg−1 for the racemization of L-to D-Ala, and 104 +/− 7 U mg−1 for the opposite direction. Comparison of Alr from S. coelicolor with orthologous enzymes from other bacteria, including the closely related D-cycloserine-resistant Alr from S. lavendulae, strongly suggests that structural features such as the hinge angle or the surface area between the monomers do not contribute to D-cycloserine resistance, and the molecular basis for resistance therefore remains elusive.

Buckling and Post-Buckling of Cantilevered Single-Walled Carbon Nanotubes in Bending

There are various potential applications in which carbon nanotubes (CNTs) may be subjected to bending in a cantilevered configuration leading to buckling which in turn may affect their electrical, electronic as well as load bearing properties. Using atomistic simulations, we study buckling and post-buckling behavior of six single-walled CNTs subjected to bending in cantilever loading (i.e., flexure in addition to shear and axial compression). Starting with small kinks on the compression side corresponding to locations of high strain energy density, ripples form on the tube wall as bending progresses, until the tube flattens maximally at a critical location giving rise to a stable hinge that rotates under continued bending. The critical buckling curvature, locations of initial and stable hinges and rotational properties of the hinge are determined. Beyond the linear elastic region, the rotational stiffness depends on the hinge angle dropping close to zero (at the same angle for each tube) before beginning to rise again, reminiscent of snap-through buckling of shells, a property that can be exploited for sensing and signal amplification applications.

Design Calculation of Micro-Displacement Amplifier Mechanism Based on Bridge Flexure Hinge

According to the microstructure characteristics of the optical components surface, the paper designs a bridge right-angle flexure hinge driven by a piezoelectric ceramic. It meets the driving micro-displacement magnification requirements and solves the coupling problem in work. Using the calculation formulas of statics and calculation formula of bending moment, the thesis explores the motion law of piezoelectric ceramics with 1KHZ excitation frequency. Through the exploration of the factors of bridge flexure hinge angle stiffness and tensile stiffness, the mathematical model of input displacement and output displacement is established. Studying the theory about the elimination of motion process coupling, it excavates the function relationships of flexure hinge angle and magnification. And the relationship is unearthed among driving force of piezoelectric ceramic, the flexure hinge stiffness, cutting force and mass of cutter system. The paper establishes their mathematical model between the above elements and the output micro-displacement, and the theoretical result is calculated by Matlab. Finally, using Pro/Engineer 3D digital modeling and analysis of simulation results by Ansys, it is found that the error can be controlled in an acceptable range by comparing the theoretical results with simulation results. Through the above analysis, the theoretical design is found to be reliable and effective.