Synthesis Of Linkages Research Articles

Acceptor Subsite Mutants of Limosilactobacillus fermentum NCC 2970 GtfB 4,3-α-Glucanotransferase Regulate the Ratio of (α1 → 3)/(α1 → 6) Linkages in Biosynthesized α-Glucans.

Limosilactobacillus fermentum NCC 2970 GtfB (Lf2970 GtfB) is the only characterized 4,3-α-glucanotransferase (4,3-α-GTase) in the glycoside hydrolase (GH) 70 family belonging to the GtfB subfamily. However, the mechanism for its (α1 → 3) linkage formation remains unclear, and the structural determinants of its linkage specificity remain to be explored. Here, sequence alignment and structural comparison were conducted to identify key amino acids that may be critical for linkage specificity. Five residues of Lf2970 GtfB (D991, G1028, A1398, T1400, and E1405), located at donor and acceptor subsites, were selected for mutation. Product structure analysis revealed that D991 and G1028, located near the acceptor binding subsites, played crucial roles in linkage formation. Besides native (α1 → 4) and (α1 → 3) linkages, mutants G1028R and D991N showed 8 and 10% (α1 → 6) linkage increases compared to 1% for wild-type in products. Additionally, molecular docking studies demonstrated that the orientation of acceptor binding in G1028R and D991N mutants was favorable for (α1 → 6) linkage synthesis. However, the mutation at positions A1398, T1400, and E1405 indicated that the donor subsites contribute less to the linkage specificity. These results shed light on the structural determinants of linkage specificity of 4,3-α-GTase Lf2970 GtfB and provided insights into the structure-function relationship of family GH70.

Fourier-Based Function Generation of Four-Bar Linkages With an Improved Sampling Points Adjustment and Sylvester's Dialytic Elimination Method

Abstract Four-bar linkages are critical fundamental elements of many mechanical systems, and their design synthesis is often mathematically complicated with iterative numerical solutions. Analytical methods based on Fourier coefficients can circumvent these difficulties but have difficulties with sampling points adjustment and solutions of the design equations in previous studies. In this paper, an improved Fourier-based analytical synthesis method is presented, which transforms the function generation synthesis of planar four-bar linkages into a problem of solving design equations. Calculation of the Fourier coefficients is discussed, including the discretization of the prescribed function and an improved sampling points adjustment method. It is shown that the Fourier coefficients can be computed efficiently and accurately by discretizing the prescribed function with a small number of sampling points. The proposed sampling adjustment method overcomes the difficulty of easily resulting in non-Grashof solutions by considering the complete period of the prescribed function. An improved Sylvester's dialytic elimination method is presented to solve design equations. The method reduces the computation time and avoids cumbersome procedures without generating additional invalid solutions. Several examples are presented to demonstrate the advantages of the proposed synthesis method, which is easy-understanding and efficient, and yields more accurate solutions than available synthesis methods.

A planar bisection strategy for multipoint path synthesis of four-bar linkages

In order to improve the global search ability of the optimization algorithm when solving the path synthesis problem, this paper proposes a synthesis method of a four-bar mechanism based on the bisection strategy of the Lévy-PSO evolutionary algorithm. First, a synthesis equation of the target point is established based on the closed-loop vector method. Use the bisection strategy to cut the hinge coordinate variation range to reduce the probability of premature maturity of the algorithm. The error algorithm of the circular proximity function is used to reduce the search dimension of the optimization algorithm and improve search efficiency. Use the improved particle swarm algorithm based on Lévy to improve global search capabilities. Four multi-point path synthesis problem examples are given to verify the effectiveness and accuracy of the method.

Stereodivergent Total Synthesis of Ethyl Plakortide Z.

Plakortides make up a subclass of marine endoperoxides with diverse biological activities. Their structural particularity is derived from the C4 and C6 positions of the endoperoxide, which are substituted by ethyl groups. The ethyl plakortide Z has the simplest side chain among its congeners and is an excellent target for testing a universal strategy for the synthesis of this subfamily. Accordingly, we have synthesized for the first time a six-membered pla-kortide using asymmetric Enders alkylation, regioselective cyclobutanol oxidative expansion, and peroxycarbenium ion-mediated diastereoselective C-C bond formation as key steps. Preparative HPLC separation of the various diastereomers yielded a pure sample of synthetic ethyl plakortide Z, constituting the first total synthesis. Despite the lack of selectivity inherent in the synthesis of peroxide linkages involving radical reactions, the diastereomer separation step was offset by an efficient synthesis in just 11 steps and 4.2% overall yield.

Complete Solutions for the Approximate Synthesis of Spherical Four-Bar Function Generators

Abstract Kinematic synthesis to meet an approximate motion specification naturally forms a constrained optimization problem. Instead of using local methods, we conduct global design searches by direct computation of all critical points. The idea is not new, but performed at scale is only possible through modern polynomial homotopy continuation solvers. Such a complete computation finds all minima, including the global, which allows for a full exploration of the design space, whereas local solvers can only find the minimum nearest to an initial guess. We form equality-constrained objective functions that pertain to the synthesis of spherical four-bar linkages for approximate function generation. We consider the general case where all mechanism dimensions may vary and a more specific case that enables the placement of ground pivots. The former optimization problem is shown to permit 268 sets of critical points, and the latter permits 61 sets. Critical points are classified as saddles or minima through a post-process eigenanalysis of the projected Hessian. The discretization points are contained within the coefficients of the stationarity polynomials, so the algebraic structure of the synthesis equations remains invariant to the number of points. The results of our computational work were used to design a mechanism that coordinates the folding wings. We also use this method to parameterize mechanism dimensions for a family of hyperbolic curves.

Path synthesis of planar four-bar linkages for closed and open curves using elliptical Fourier descriptors

Path synthesis of planar four-bar linkages for closed and open curves using elliptical Fourier descriptors

Nickel (II) imidazol-2-ylidine Complexes Supported Through Internally Functionalized Amido Linkage Synthesis and Catalytic Studies for Suzuki Miyaura Cross Coupling

Nickel (II) imidazol-2-ylidine Complexes Supported Through Internally Functionalized Amido Linkage Synthesis and Catalytic Studies for Suzuki Miyaura Cross Coupling

Computing complete solution sets for approximate four-bar path synthesis

The approximate path synthesis of four-bar linkages has been framed and solved with many different optimization techniques. Here we present a polynomial objective that is invariant to the number of approximate design positions selected, and a solution technique capable of finding all minima. The invariance property caps compute time despite increasing the size of input task specification data. This is performed by collecting a variable amount of task data into an invariable number of polynomial coefficients, called moments, before numerical optimization begins. The minima are found by applying the method of random monodromy loops to the zero gradient polynomial system of the aforementioned objective. This procedure finds all critical points, including the local and global minimum, and provides an in-process estimate of the percentage of critical points found. We applied our methodology to four-bar path synthesis problems of various computational scales by altering dimensional pre-specifications. The most general case was estimated to have 1,820,238 ± 3810 critical points, while pre-specification of one or two ground pivots yielded 26,052 and 503 roots, respectively, as validated by a trace test. The results are applied to a variety of examples.

The Retaining Pse5Ac7Ac Pseudaminyltransferase KpsS1 Defines a Previously Unreported glycosyltransferase family (GT118).

Cell surface sugar 5,7-diacetyl pseudaminic acid (Pse5Ac7Ac) is a bacterial analogue of the ubiquitous sialic acid, Neu5Ac, and contributes to the virulence of a number of multidrug resistant bacteria, including ESKAPE pathogens Pseudomonas aeruginosa, and Acinetobacter baumannii. Despite its discovery in the surface glycans of bacteria over thirty years ago, to date no glycosyltransferase enzymes (GTs) dedicated to the synthesis of a pseudaminic acid glycosidic linkage have been unequivocally characterised in vitro. Herein we demonstrate that A. baumannii KpsS1 is a dedicated pseudaminyltransferase enzyme (PseT) which constructs a Pse5Ac7Ac-α(2,6)-Glcp linkage, and proceeds with retention of anomeric configuration. We utilise this PseT activity in tandem with the biosynthetic enzymes required for CMP-Pse5Ac7Ac assembly, in a two-pot, seven enzyme synthesis of an α-linked Pse5Ac7Ac glycoside. Due to its unique activity and protein sequence, we also assign KpsS1 as the prototypical member of a previously unreported GT family (GT118).

The Retaining Pse5Ac7Ac Pseudaminyltransferase KpsS1 Defines a Previously Unreported glycosyltransferase family (GT118)

AbstractCell surface sugar 5,7‐diacetyl pseudaminic acid (Pse5Ac7Ac) is a bacterial analogue of the ubiquitous sialic acid, Neu5Ac, and contributes to the virulence of a number of multidrug resistant bacteria, including ESKAPE pathogens Pseudomonas aeruginosa, and Acinetobacter baumannii. Despite its discovery in the surface glycans of bacteria over thirty years ago, to date no glycosyltransferase enzymes (GTs) dedicated to the synthesis of a pseudaminic acid glycosidic linkage have been unequivocally characterised in vitro. Herein we demonstrate that A. baumannii KpsS1 is a dedicated pseudaminyltransferase enzyme (PseT) which constructs a Pse5Ac7Ac‐α(2,6)‐Glcp linkage, and proceeds with retention of anomeric configuration. We utilise this PseT activity in tandem with the biosynthetic enzymes required for CMP‐Pse5Ac7Ac assembly, in a two‐pot, seven enzyme synthesis of an α‐linked Pse5Ac7Ac glycoside. Due to its unique activity and protein sequence, we also assign KpsS1 as the prototypical member of a previously unreported GT family (GT118).

Atroposelective Total Synthesis of Cihunamide B.

A short, atroposelective synthesis of cihunamide B (1) is reported. The feature of this report is the decagram-scale SNAr reaction of l-tryptophan derivatives, followed by atroposelective Larock macrocyclization. This strategy allowed the construction of a Trp-Trp cross-linkage with unprecedented atropisomerism. The atroposelectivity of this Larock macrocyclization has been investigated through a combination of experimental and computational chemistry, yielding detailed insights into the synthesis of biaryl linkages. It also enabled the concise synthesis of cihunamide B (1), which is expected to be a potential antibacterial agent.

A Bi-Invariant Approach to Approximate Motion Synthesis of Planar Four-Bar Linkage

This paper presents a planar four-bar approximate motion synthesis technique that uses only pole locations. Synthesis for rigid-body guidance determines the linkage dimensions that guide a body in a desired manner. The desired motion is specified with task positions including a location and orientation angle. Approximation motion synthesis is necessary when an exact match to the task positions cannot be obtained. A linkage that achieves the task positions as closely as possible becomes desired. Structural error refers to the deviations between the task positions and the linkage’s generated positions. A challenge in approximate motion synthesis is that structural error involves metrics that include location and orientation. A best-fit solution is not evident because the structural error is based on an objective function that combines the location and orientation. Such solutions lack bi-invariance because a change in reference for the motion changes the values of the metric. This work uses only displacement poles, described solely by their coordinates, as they sufficiently characterize the relative task positions. The optimization seeks to minimize the distance between the poles of the task positions and the poles of the generated positions. The use of poles results in a bi-invariant statement of the problem.

A differential evolution algorithm combined with Lévy Flight for dimensional synthesis of four-bar linkage

The paper considers dimensional synthesis of a path generator four-bar linkage by applying the modified Differential Evolution (DE) algorithm. During the search of the space, the DE algorithm may skip the right solution and lead to premature convergence. If the step is reduced, the search space is reduced as well, so that convergence becomes slower. Search efficiency may be achieved by including Lévy Flight in the DE algorithm. Namely, when the DE algorithm identifies the space of best solution, then a Levý Flight step is used for local search in that region, which significantly increases the exploitation capability and allows obtaining a very efficient solution of the optimization problem. The algorithm was tested with three examples of dimensional synthesis of a path generator four-bar linkage. The proposed algorithm can be very efficiently applied to solving very complex optimization problems.

Algebraic synthesis and input-output analysis of 1-DOF multi-loop linkages with a constant transmission ratio between two adjacent parallel, intersecting or skew axes

This paper deals with the algebraic synthesis and input-output analysis of one degree-of-freedom (1-DOF) multi-loop planar, spherical, and spatial linkages for increasing or decreasing angular motion with a desired constant transmission ratio between two adjacent parallel, intersecting, and skew axes respectively. Based on the rotation scaling model and motion polynomials over dual quaternions, an algebraic synthesis method including three procedures is proposed to exactly construct novel multi-loop linkages owning arbitrarily prescribed constant transmission ratios and input/output axes. To illustrate this method, several 1-DOF multi-loop planar, spherical, and spatial linkages for rotation scaling are synthesized by designating various input and output axes as well as transmission ratios. Taking some multi-loop planar, spherical, and spatial linkages as examples, input-output analysis is carried out to verify their transmission characteristics. The results demonstrate that the generated 1-DOF multi-loop linkages can indeed transmit motion with prescribed constant transmission ratios and input/output axes. This work provides a framework for further investigation on mechanisms performing specified tasks for motion transmission.

On the exact motion synthesis of planar four-bar-linkages with prismatic and revolute joints

This paper introduces a novel and simple approach that can be used in the exact motion synthesis of planar four-bar linkages with prismatic (P) and revolute (R) joints to up four given poses. Only basic knowledge of vectors is required and does not depend on either, advanced concepts of kinematic mapping or cumbersome graphic skills. As a result, the design equations are very simple, and they can provide up to a maximum of twenty solutions, which can be real or imaginary. Each pair of different real solutions allows the design of a mechanism that can accurately achieve the given poses. The details of the methodology are illustrated by considering several challenging examples found in the literature.

Design of the five-bar linkage with singularity-free workspace

AbstractThis paper shows the kinematic analysis and the synthesis of the five-bar linkage with symmetrical structure and singularity-free dexterous workspace. The type synthesis of the five-bar linkage shows that the number of symmetrical structures of five-bar linkage is limited to eight structures. This study deals with the forward and inverse kinematic analysis and synthesis of the five-bar structure 5-RRRRR. The synthesis equations allow the analytical computation of the link lengths of a symmetrical five-bar linkage using only revolute joints to avoid the singularities in an imposed dexterous workspace. A numerical example of the symmetrical five-bar linkage is analyzed and synthetized theoretically and characterized by computing the performance indices. The tests on an experimental model of the five-bar linkage 5-RRRRR confirm the singularity-free dexterous workspace.

Multi-objective optimization and driving mechanism design for controllable wings of underwater gliders

Recently, underwater glider has become an effective tool for long-term ocean exploration. Controllable wing technology, which can improve comprehensive performance of underwater glider, has received widespread attention. This paper mainly proposes a multi-objective optimization based design method of controllable wings for underwater gliders. First, controllable wing configuration parameters are determined, specifically including wing span and sweep angle here. Then, hydrodynamic equations, containing controllable wing configuration parameters, are obtained by CFD simulation and quartic polynomial fitting. On this basis, the glider performance analysis model, quantitatively evaluating voyage velocity, static stability and energy consumption, are derived, and multi-objective optimization model of wing configuration parameters is established. Meanwhile, the relationship between controllable wing configuration parameters and the glider comprehensive performance is discussed. Especially, surrogate model technology is introduced into optimization calculation process to improve optimization efficiency. And non-dominated sorting genetic algorithm II is employed to obtain Pareto optimal set, which will make design objectives of driving mechanism of controllable wings clearer. Based on multi-objective optimization results and linkage synthesis method, a novel driving mechanism of controllable wings is designed, and corresponding principle prototype is manufactured. Besides, the motion characteristic, sealing and locking methods of the design scheme are also discussed.

Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs

Phosphorus Fluoride Exchange (PFEx) represents a cutting-edge advancement in catalytic click-reaction technology. Drawing inspiration from Nature's phosphate connectors, PFEx facilitates the reliable coupling of P(V)-F loaded hubs with aryl alcohols, alkyl alcohols, and amines to produce stable, multidimensional P(V)-O and P(V)-N linked products. The rate of P-F exchange is significantly enhanced by Lewis amine base catalysis, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). PFEx substrates containing multiple P-F bonds are capable of selective, serial exchange reactions via judicious catalyst selection. In fewer than four synthetic steps, controlled projections can be deliberately incorporated along three of the four tetrahedral axes departing from the P(V) central hub, thus taking full advantage of the potential for generating three-dimensional diversity. Furthermore, late-stage functionalization of drugs and drug fragments can be achieved with the polyvalent PFEx hub, hexafluorocyclotriphosphazene (HFP), as has been demonstrated in prior research.

Finding straight line generators through the approximate synthesis of symmetric four-bar coupler curves

The approximate path synthesis of four-bar linkages with symmetric coupler curves is presented. This includes the formulation of a polynomial optimization problem, a characterization of the maximum number of critical points, a complete numerical solution by homotopy continuation, and application to the design of straight line generators. Our approach specifies a desired curve and finds several optimal four-bar linkages with a coupler trace that approximates it. The objective posed simultaneously enforces kinematic accuracy, loop closure, and leads to polynomial first order necessary conditions with a structure that remains the same for any desired trace leading to a generalized result. Ground pivot locations are set as chosen parameters, and it is shown that the objective has a maximum of 73 critical points. The theoretical work is applied to the design of straight line paths. Parameter homotopy runs are executed for 1440 different choices of ground pivots for a thorough exploration. These computations found the expected linkages, namely, Watt, Evans, Roberts, Chebyshev, and other previously unreported linkages which are organized into a 2D atlas using the UMAP algorithm.

Synthesis of Four-Bar Linkages by Four Infinitely Close Relative Positions and Pressure Angle

A computer-applicable linear mathematical model has been developed to determine Burmester’s curves for infinitely close relative positions (cubic of stationary curvature), which indirectly uses Carter-Hall’s circle. By varying a free parameter and using elements of kinematic and analytical geometry, an incomparably simpler solution is achieved than that obtained by the third-degree equations of the Burmester's curves for stationary curvature. The mathematical model for the synthesis of four-bar linkages includes and a condition for the pressure angle, whereupon is uniquely defined the kinematic diagram of the mechanism. Of the pressure angle, the reactions of the forces in the kinematic pairs and the force sizing of the mechanism depend. The model would facilitate the engineers in the synthesis of four-bar linkages by generating a function approximating a given function in the vicinity of a given position, where the two functions have four infinitely close common points (3rd-order approximation). An example of the synthesis of a four-bar linkage illustrates the application of the model, which is linear - it includes only equations of straight lines written in Cartesian coordinates, which is why it is convenient for computer calculations.