Kinetic Balance Research Articles

Experimental and computational evaluation of the degree of micro-collapse formations in freeze-dried cakes

The quality of freeze-dried products is intensely related to the occurrence of collapse. In this regard, the present study was aimed at developing a method to quantitatively evaluate and predict the degree of collapse of freeze-dried products, which has not been established to date, based on the operating conditions of the freeze-drying process. Freeze-dried specimens were prepared using dextrins with different glass transition temperatures and analyzed by X-ray computed tomography. The deformation of the freeze-dried-cake microstructure was evaluated using a shape factor (i.e., the mean circularity of the fragmented domain) as an index of the occurrence of collapse. The obtained shape factors increased with the degree of collapse and varied between 0.5 and 1.0; moreover, they adequately correlated with the values obtained by tapped density experiments. The deformation of the fragmented domain during freeze-drying was analyzed using computational fluid dynamics simulations, assuming surface-tension-induced deformation during dehydration under non-isothermal conditions. The results confirmed that the microstructural changes in the freeze-dried cakes were determined by the kinetic balance between viscous flow and water removal from the matrix, and the validity of employing the proposed shape factor as an indicator of micro-collapse was demonstrated.

The effect of kinetic balance exercises in developing the jumping and shooting skills of players under 16 years old in basketball

The game of basketball requires comprehensive preparation in all physical and skillful aspects as well as tactical, psychological and educational aspects. This is achieved through the preparation of comprehensive training curricula in order to develop players, including young people, as they are the basis for achieving the best results and reaching a high level. Through the experience of the researcher and his familiarity with some research and training curricula, he saw that these curricula and research did not allocate a large amount of their contents to the characteristic of carrying the combined offensive performance, as well as a lack of interest in this ability, which negatively affected the performance of young players for the skill (v.cat, receiving the ball, then shooting peacefully, Offensive reservation, receiving the ball and then peaceful shooting, deception from stability, receiving the ball and then shooting peacefully) a clear description when performing it, and therefore because this skill always leads to difficult conditions and the presence of a defender nearby, which negatively affects the results of the match. The aim of the research is to prepare complex exercises in developing offensive skills Vehicle for young basketball players. Identifying the impact of vehicle exercises in developing the jumping and shooting skills of players under 16 years old in basketball. As for the research hypothesis, the combined exercises had a positive effect on developing the offensive skills of the young basketball players. The researcher used the experimental method as a research measure commensurate with the research objectives. The research community consisted of the Air Defense Club basketball players under 16 years old, who numbered 12 players, where the community was randomly divided into two groups (experimental and control), where the number of each group reached (6) players. Youth basketball for the experimental group and the control group. One of the most important recommendations is interest in developing physical abilities in a way that precedes and accompanies the development of offensive skills for young basketball players.

Two-dimensional Bi2WxMo1−xO6 solid solution nanosheets for enhanced photocatalytic toluene oxidation to benzaldehyde

Two-dimensional (2D) Bi2WO6, Bi2MoO6, and Bi2WxMo1−xO6 (x = 0.1, 0.3, 0.5, 0.7, and 0.9) solid solution photocatalysts were synthesized using the hexadecyl trimethyl ammonium bromide-assisted hydrothermal method. All of the samples displayed a morphology of irregularly rectangular nanosheets with a thickness of 7.0–17.4 nm. The photocatalytic performance of Bi2WxMo1−xO6 was much better than that of Bi2MoO6 or Bi2WO6 for the selective oxidation of toluene, with the Bi2W0.3Mo0.7O6 solid solution showing the highest benzaldehyde formation rate (1663 μmol/(g h)), which was about 1.95 and 2.83 times higher than those obtained over Bi2MoO6 and Bi2WO6, respectively. Furthermore, 91% benzaldehyde selectivity and excellent stability were also achieved over Bi2W0.3Mo0.7O6. The enhancement in photocatalytic activity of Bi2W0.3Mo0.7O6 was attributable to the balance of fast charge kinetics and optimized energy band structure. The results of the reactive species trapping and active radicals detection experiments reveal that the photogenerated holes, superoxide species, and carbon-centered radicals might play the important roles in the generation of benzaldehyde, and the possible photocatalytic toluene oxidation mechanisms over Bi2W0.3Mo0.7O6 were accordingly proposed.

재활승마가 지적장애 성인의 평형성에 미치는 영향

The main purpose of the study was to analyze the effects of therapeutic horseback riding on the balance of adults with intellectual disability by appling the biomechanics equipment of sole pressure measurement. This study was conducted on 20 adults with intellectual disabilities who can communicate and not restricted of physical activity.<BR> The followings are the major findings of the analysis. The measurement of stance and gait by biomechanics factors to find out the transition of physical balance changes of the samples, before and after the therapeutic horseback riding program intervention, resulted can not enhanced static and kinetic balance of adults with intellectual disabilities.<BR> Therapeutic horseback riding increases the amount of physical activity of people with intellectual disabilities and improves the health and quality of life of people with intellectual disabilities. Unfortunately, however, this study targeted adults with intellectual disabilities in their mid-40s who had no prior experience in participation, lack of time, and physical activity, making it difficult to draw positive and distinct effects of therapeutic horseback riding. However, the 24-week therapeutic horseback riding program was not statistically significant, but a positive range of changes is considered necessary to establish a better therapeutic horseback riding program for adults with intellectual disabilities by setting various research methods.

Kinetic Method of Producing Pores Inside Protein-Based Biomaterials without Compromising Their Structural Integrity.

Hydrogels made from globular proteins cross-linked covalently into a stable network are becoming an important type of biomaterial, with applications in artificial tissue design and cell culture scaffolds, and represent a promising system to study the mechanical and biochemical unfolding of proteins in crowded environments. Due to the small size of the globular protein domains, typically 2-5 nm, the primary network allows for a limited transfer of protein molecules and prevents the passing of particles and aggregates with dimensions over 100 nm. Here, we demonstrate a method to produce protein materials with micrometer-sized pores and increased permeability. Our approach relies on forming two competing networks: a covalent network made from cross-linked bovine serum albumin (BSA) proteins via a light-activated reaction and a physical network triggered by the aggregation of a polysaccharide, alginate, in the presence of Ca2+ ions. By fine-tuning the reaction times, we produce porous-protein hydrogels that retain the mechanical characteristics of their less-porous counterparts. We further describe a simple model to investigate the kinetic balance between the nucleation of alginate and cross-linking of BSA molecules and find the upper rate of the alginate aggregation reaction driving pore formation. By enabling a more significant permeability for protein-based materials without compromising their mechanical response, our method opens new vistas into studying protein-protein interactions and cell growth and designing novel affinity methods.

Acute Impact of Proprioceptive Exercise on Proprioception and Balance in Athletes

This study aimed to compare the acute effect of a proprioceptive exercise session and a non-specific exercise session on knee position sense, and the static and dynamic balance of athletes. Sixty male athletes (19.4 ± 1.2 years) participated in a within-subjects repeated-measures study. Knee position sense in closed kinetic chain, and static (BESS test) and dynamic balance (Y-balance test) were measured before and after two exercise sessions, consisting of 10 min of non-specific exercise in a cycle-ergometer or proprioceptive exercise with an unstable platform. Overall, both exercise sessions significantly improved knee position sense, BESS score, and YBT composite score, and no differences were detected between proprioceptive and non-specific sessions (knee position sense, −6.9 ± 65.2% vs. −11.5 ± 75.0%, p = 0.680; BESS, −19.3 ± 47.7% vs. −29.03 ± 23.5%, p = 0.121; YBT, 2.6 ± 2.7% vs. 2.2 ± 2.2%, p = 0.305). Twenty athletes did not improve knee position sense after the exercise session (non-responders). When analyzing only the exercise responders, both sessions improved knee position sense, but the improvement was greater after the proprioceptive exercise session (56.4 ± 25.6% vs. 43.8 ± 18.9%, p = 0.023). In conclusion, a single proprioceptive, as well as non-specific, exercise session increased knee position sense and balance. The proprioceptive exercise seems to be more effective in improving joint position sense when considering only athletes who respond to the intervention.

Flow Regimes and Mixing of Dissimilar Fluids in T‐Jets Mixers

AbstractEfficient mixing conditions for similar fluids in T‐Jets mixers are well‐established. This paper extends the characterization of the mixing of dissimilar fluids. Planar laser‐induced fluorescence images were captured using fluids with a viscosity ratio between 1.2 and 3. Flow visualizations showed that the best mixing conditions are achieved when the jets are well‐balanced, and the onset of a chaotic flow regime is determined by the Reynolds number of the more viscous fluid (ReHjet &gt; 100). Computational fluid dynamics simulations were also performed to get deeper insight into the flow field and mixing dynamics, enabling the prediction of the impingement point position. An analytical model based on jets' kinetic energy rate balance is proposed as a design tool to predict the impingement point position.

Comparison of normalized and non-normalized block caving comminution models

In block cave mining, rock fragmentation is a key parameter that influences the production level design and mine planning. Fragmentation occurs mainly by natural breakage during the caving process and in the draw column. The breakage that occurs within the column is known as secondary fragmentation. Secondary fragmentation has been successfully described using the block caving comminution model, which replicates the fragmentation mechanics between particles under drawn and vertical loads in a draw column. This model is based on a kinetic and population balance approach, in which non-normalized and normalized assumptions can be used depending on material and comminution system behaviour. In this paper, the non-normalized and normalized approaches are applied and compared to laboratory data to determine which assumption should be used for secondary breakage in block caving. Approaches are compared graphically, with the mean square error and the Fisher test with a false-rejection probability of 0.05. Based on a statistical analysis, the results show that the normalized model can be applied to all the rock types tested.

Differential Contribution of Protein Factors and 70S Ribosome to Elongation.

The growth of the polypeptide chain occurs due to the fast and coordinated work of the ribosome and protein elongation factors, EF-Tu and EF-G. However, the exact contribution of each of these components in the overall balance of translation kinetics remains not fully understood. We created an in vitro translation system Escherichia coli replacing either elongation factor with heterologous thermophilic protein from Thermus thermophilus. The rates of the A-site binding and decoding reactions decreased an order of magnitude in the presence of thermophilic EF-Tu, indicating that the kinetics of aminoacyl-tRNA delivery depends on the properties of the elongation factor. On the contrary, thermophilic EF-G demonstrated the same translocation kinetics as a mesophilic protein. Effects of translocation inhibitors (spectinomycin, hygromycin B, viomycin and streptomycin) were also similar for both proteins. Thus, the process of translocation largely relies on the interaction of tRNAs and the ribosome and can be efficiently catalysed by thermophilic EF-G even at suboptimal temperatures.

Development of the kinetically and atomically balanced generalized pseudospectral method

The kinetically and atomically balanced conditions have been extensively used in various basis-set expansion methods to remove the nonphysical spurious states appearing in the numerical calculation of the Dirac equation; however, they are generally not applicable for methods in discrete variable representation. In this paper we show that these conditions can be conveniently introduced into the generalized pseudospectral (GPS) method. Four types of balanced condition, the mono kinetic balance (MKB), dual kinetic balance, mono atomic balance (MAB), and dual atomic balance, are incorporated into the GPS method to eliminate the spurious states. Numerical calculations for a variety of bound states of H-like ions in point-charge models are compared with the analytical solutions to demonstrate the accuracy and efficiency of the developed methods. The application to highly charged ions with extended nuclear models is performed to show the flexibility of the balanced GPS methods in practical atomic structure calculations. It is concluded that the MAB-GPS and MKB-GPS methods, which are both free of any spurious states, show better performance and simpler implementation than the others in solving the Dirac equation with the potential in point-charge and extended nuclear models, respectively. The balanced GPS methods developed in this paper provide a useful tool for accurately solving the one-electron Dirac equation and efficiently constructing the multielectron relativistic wave functions.

Investigation of CO2 hydrate slurry flow characteristics with particle dissociation for carbon storage and transportation

CO2 capture and storage technology is an effective method to mitigate the greenhouse effect and hydrate slurry is a high-efficiency way of CO2 transportation. In this study, in order to further reduce the cost and improve the transportability, a new CO2 hydrate slurry transport mode which allows a small part of hydrate particles to dissociate during flow process is proposed. To investigate the CO2 hydrate slurry flow characteristics and particle micro behaviors, a multiphase flow model coupled with hydrate dissociation kinetic model and population balance model is established. Experimental results are used to verify this integrated model. Furthermore, the effects of hydrate dissociation on CO2 transportability are also analyzed. The results indicate that the dissociation rate of hydrate during flow process can be divided into rapid dissociation stage and weakened dissociation rate stage. The agglomeration of hydrate particle can reduce the total surface area, further resisting the dissociation rate. The hydrate particle size experiences a process of growing to dynamic balance. The hydrate dissociation can decrease the mean viscosity of CO2 hydrate slurry flow, which can reduce the pressure drop and energy loss compared with the flow without hydrate dissociation. The generated bubbles can accelerate the CO2 hydrate slurry flow, increasing the transportability and reducing the risk of hydrate blockage in pipe induced by agglomeration.

NMR Indirect Spin–Spin Coupling Constants in a Modern Quasi-Relativistic Density Functional Framework

A quasi-relativistic implementation of NMR indirect spin-spin coupling constants is presented. The exact two-component (X2C) Hamiltonian and its diagonal local approximation to the unitary decoupling transformation (DLU) are utilized together with the (modified) screened nuclear spin-orbit approach. In a restricted kinetic balance, the finite nucleus model is available for both the scalar and vector potentials. The implementation supports density functionals up to the fourth rung of Jacob's ladder, i.e., (range-separated) hybrid and local hybrid functionals based on a seminumerical ansatz. We assess the quality of our quasi-relativistic X2C approach by comparison with "fully" relativistic four-component results for small main-group molecules and alkynyl compounds. The mean absolute error introduced by the DLU scheme is less than 0.05 × 1019 T J-2 of the reduced coupling constant for the small main-group molecules and 0.5 Hz for the alkynyl compounds. Thus, the error is significantly smaller than finite nucleus size effects for heavy elements. The basis set convergence and the impact of different density functional approximations are further studied. We propose a simple scheme to develop segmented-contracted relativistic all-electron basis sets for NMR spin-spin couplings. Our implementation allows us to perform calculations of extended molecules with reasonable computational effort, which is illustrated for the 1J(119Sn, 31P) coupling constant of a low-valent tin phosphinidenide complex. The corresponding results are in good agreement with the experimental findings.

A Pseudo-matrix model coupled to a particle selection algorithm for simulating batch grinding

The kinetic population balance model (PBM) is widely used to predict the particle size distributions of ball milling products. The matrix model can be easily used for the same purpose if the grinding time can be incorporated into the relevant model. This study proposes and demonstrates an accurate algorithm that uses a pseudo-matrix model to simulate the product size distributions (PSDs) of successive breakage events in batch grinding. The simulation results indicate that the breakage events in the mills may be determined by attraction forces between particles and grinding media. The algorithm is shown to be widely applicable to different combinations of samples and grinding equipment. The algorithm can even work with arbitrary sets of parameters that are irrelevant to the mill feed. Therefore, the proposed algorithm with its mathematical framework may be fundamental to different size reduction methods. Also, the algorithm is shown to have a potential for predicting the product PSDs of continuous milling.

A Model for Bias Potential Effects on the Effective Langmuir Adsorption–Desorption Processes

We discuss the foundations of a model based on an extension of the Langmuir approximation for the adsorption–desorption phenomena, in which the phenomenological coefficients depend on the bias potential, in addition to their dependence on the adsorption energy. The theoretical analysis focuses on the effect of these effective coefficients on the electrical response of an electrolytic cell to an external electric field, as predicted by the Poisson–Nernst–Planck model. Kinetic balance equations govern the current densities on the electrodes when the adsorption phenomenon occurs in the presence of an electric bias. The influence of the phenomenological parameters entering the model, as well as of the symmetry of the cell on the cyclic voltammetry, is investigated.

Model Analysis of the Role of Kinetics, Adsorption Capacity, and Heat and Mass Transfer Effects in Sorption Enhanced Dimethyl Ether Synthesis.

The role of kinetics, adsorption capacity, and heat and mass transfer effects in the sorption enhanced dimethyl ether synthesis (SEDMES) is investigated by means of a 2D+1D model of a single tube of an industrial-scale, externally cooled, multitubular reactor that simulates the reaction/adsorption step of the SEDMES cycle. The effect of the adsorbent/catalyst weight ratio is analyzed, showing that a trade-off between DME productivity and yield originates from the balance of kinetics and adsorption capacity in the reactor tube. The effects of internal diffusion in catalyst particles are shown to have a strong impact on effective reaction rates: significant yield/productivity improvements are obtained when using a mechanical mixture of catalysts with small particle diameters or by rearranging the distribution of the two active phases in hybrid or core@shell pellets. The thermal effects in the reactor, which are increasingly critical upon intensifying the SEDMES process conditions, are also addressed.

Effect of Mo addition on the pitting resistance of TiMn alloys in Hanks’ solution

A family of TiMn alloys having a comparable mechanical property to Ti6Al4V alloy was developed for biomedical applications. Addition of 3–4 wt% Mo was found to improve corrosion resistance of the alloys to a level of that of commercial pure Ti. The effect of Mo to the electrochemical parameters of the passive film was not yet clarified. This work evaluated the effect of Mo on pitting resistance of Ti6Mn4Mo (TiMnMo) alloy in Hanks’ solution using electrochemical techniques combined with SEM, AFM and XPS analyses. Electrochemically, the TiMnMo demonstrated a higher resistance to uniform corrosion than Ti6Mn (TiMn) with a re-passivation and restoration ability against pitting corrosion which was not observed on TiMn. The TiMnMo showed a non-diffusional corrosion characteristic due to a denser passive film than that of TiMn. The SEM and AFM observation revealed a more severe pitting formation on TiMn than on TiMnMo. The XPS analysis confirmed the presence of Mo and Mn oxides that reinforced the TiO2 matrix. The mechanism of the different passivation behaviors of the two alloys is described according to the point defect model that based on the balance of kinetics of the oxide layer growth and dissolution reactions.

CO2 Removal Using Adsorption Onboard A Floating Production Storage and Offloading (FPSO) Vessel

Offshore operations gas purification has always been limited to the marketable associated value of the gas where purification would either be onsite or sent to surface facilities for treatment. CO2 and H2S removal and gas sweetening in remote offshore locations is for the most part non-existent and CO2 is either being released into the atmosphere, within the acceptable operation limit of the platform, or being captured using conventional techniques with physical solvents such as in the selexol, rectisol, or sulfinol processes. Approximately 429.61 kg of CO2 exists in a 42-gallon barrel of distillate fuel oil and a CO2 coefficient of 0.0549 kg exists in 1 cubic foot of gas thereby emphasizing the need for an engineering solution on floating production storage and offloading (FPSO) units [1]. With strict regulation on greenhouse gases, it is increasingly paramount to utilize engineering measures to provide a contingency plan in mitigating carbon footprint with emerging novel technologies. The purpose of this study is to retrofit an existing FPSO with a CO2 capture plant; the efficiency of the capture plant, its capture capacity, and energy requirement based on experimental data will be thoroughly investigated during the scale up procedure. The research proceedings will require the use of a plethora of simulation suites which include Autodesk Fusion 360 for plant design. Further simulation will be carried out with numerical suites using Mathcad Prime 3.0 to study the scale up procedure from experimental to industrial sized adsorption unit complete with dimensions, energy requirement, capture capacity, and thermal values. The FPSO in figure 1 above presented by (Araujo et al., 2016) indicates the availability of a capture plant as part of the process train on an FPSO. Efficiency loss contribution to the system may be deduced but also it is relevant to note the custom nature of the FPSO design being independent in its operation mode compared to other profiles. The availability of the stage compressors, dehydration units, and steam generation plant as part of the FPSO operation aid in minimising the need for additional equipment for the adsorption plant, however investigation has to be made on the redirecting of processes to serve the additional components highlighted above. Primary results have shown a low tendency for dual adsorption from the initial kinetic stoichiometric balance which could also be due to the force field parameters and charges affecting the active sites. For the current concept the fixed bed experimental model from the Research and Innovation Centre on CO2 and H2 is scaled up numerically to a fixed bed height of 6.56 feet, and filled with precipitated silica impregnated with PEI solution pressurized with CO2 inflow rated at 13 lb/hr at a fixed 1.2 Bar 60°C. The operational nature of the FPSO will be modified to account for the changes requested in gas sweetening and capture programs or enhanced oil recovery. Results from the simulation will also assist in providing a tangible and relatable understanding to the complexity of solid sorption technology integration within existing processing plants. The findings of this study will help comprehend the viability of an integrated adsorption plant within an existing process train. The efficiency of the plant operation for an oil production offshore facility with associated gas or for a standalone gas field will be addressed using a feasibility study conducted for the purpose of sustainable offshore operations.

ТЕОРЕМА ОБ ИЗМЕНЕНИИ ЭНЕРГИЙ ПАРЦИАЛЬНЫХ ДВИЖЕНИЙ ГОЛОНОМНЫХ МЕХАНИЧЕСКИХ, ЭЛЕКТРИЧЕСКИХ И ЭЛЕКТРОМЕХАНИЧЕСКИХ СИСТЕМ С НЕСКОЛЬКИМИ СТЕПЕНЯМИ СВОБОДЫ

The purpose of this research is to formulate and prove the principle of energy of partial subsystems for mechanical, electrical, and electromechanical holonomic systems with time-independent constraints, as well as the development of a simple method to derive equations of motion for such systems. This principle is helpful in giving short courses of theoretical mechanics to students who know only the basic principle of energy and the D’Alembert principle. Two issues are covered in this paper: firstly, the formulation of the principle of energies for interacting mechanical partial subsystems, including the proof of the theorem, and, finally, the application of the developed method for mechanical, electrical, and electromechanical systems. The energy principle is developed using the D’Alembert principle for partial motions of the system when deriving kinetic and power balance equations. For electrical and electromechanical systems, the principle is based on the first electromechanical analogy of Maxwell’s postulate and Kirchhoff 's laws. As examples, the principle allowed obtaining equations of motion of mechanical systems with three degrees of freedom: rotation of a disk on an elastic shaft, dynamics of a vibration table, an electrical system with two cyclic currents connected through a resistor, and an electromechanical system of the acceleration sensor.

Kinetic-matching between electrodes and electrolyte enabling solid-state sodium-ion capacitors with improved voltage output and ultra-long cyclability

Broader context: A kinetic-matched bilayer ionogel electrolyte and an ultra-high kinetic anode were proposed to overcome the kinetic imbalance in solid-state sodium-ion capacitors. The COMSOL Multiphysics simulation proved that as-formed asymmetrical ionogel electrolyte could efficiently weaken the concentration gradient up to 0.3 M at 5 A g −1 and relieve polarization. A sodium-ion capacitor exhibited high energy density of 94.8 Wh kg −1 at 1925.0 W kg -1 and ultra-long-term ability of 10,000 cycles within 4.0 V owing to the double kinetic-matchings design. • A new kinetic-matched design was proposed for solid-state sodium-ion capacitors. • An ultra-high kinetic anode was fabricated via a “Phase Engineering” route. • A COMSOL simulation verified the function of the asymmetric ionogel electrolyte. • The kinetic-balanced sodium-ion capacitor exhibited high stability of 10,000 cycles. Sodium-ion capacitors (SICs) are attracting extensive attentions owing to their high energy density and the availability of abundant sodium element. However, kinetic imbalance between cathodes and anodes or between electrodes and electrolytes at interfaces originating from different ions storage mechanisms need to be well minimized. Thus, it is significant to design specific ion-matching enabled electrodes and electrolytes. Here, an ultra-high kinetic TiO 2 (A)/TiO 2 (B)@C/CNT nanohybrid electrode with rich textured interfaces and a capacity of 251 mAh g −1 was fabricated via a “Phase Engineering” route. In particular, the effects induced by cubic and monoclinic phases were distinguished by an In-situ XRD technique. Moreover, a bi-layered ternary ionogel electrolyte was constructed to achieve optimal kinetic balance and ion matching. Impressively, the optimized bilayer solid electrolyte exhibited an ionic conductivity of 5.22 × 10 -3 S cm −1 and a high Na + transference number of ~ 0.611, resulting to a weakened concentration gradient of 0.3 M at 5 A g −1 and enhanced intercalation/deintercalation of Na + at the anode/electrolyte interface. The enhanced kinetic matching was verified by a COMSOL Multiphysics simulation. Significantly, the double-kinetic-matching design on both electrodes and electrolyte rendered a sodium-ion capacitor (SIC) with an energy density of 94.8 Wh kg −1 at 1925.0 W kg −1 and an ultra-long cyclability of 10,000 cycles at an effective operating potential of 4.0 V. This work demonstrates an effective strategy to high performance solid-state sodium-ion capacitors via the synergistic optimization of electrodes and electrolyte and highlights the importance of understanding the kinetic matching.

Ruthenium(III) complexes with imidazole ligands that modulate the aggregation of the amyloid-β peptide via hydrophobic interactions

Alzheimer's disease (AD) is the most common form of dementia, characterized by extracellular protein deposits, comprised primarily of the peptide amyloid-beta (Aβ), are a pathological indicator of the disease. Commonly known as Aβ plaques, these deposits contain a relatively high concentration of metals, making metallotherapeutics uniquely suited to target soluble Aβ, thereby limiting its aggregation and cytotoxicity. Ruthenium-based complexes are promising candidates for advancement, as the complex PMRU20 (2-aminothiazolium [trans-RuCl4(2-aminothiazole)2]) and several thiazole-based derivatives were found to prevent the aggregation of Aβ, with hydrogen-bonding functional groups improving their performance. Further investigation into the impact of the heteroatom in the azole ring on the activity of Ru complexes was achieved through the synthesis and evaluation of a small set of imidazole-based compounds. The ability of the complexes to prevent the aggregation of Aβ was determined where the same sample was subjected to analysis by three complementary methods: ThT fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM). It was found that hydrophobic interactions, along with hydrogen-bonding via the imidazole nitrogen heteroatom, promoted interactions with the Aβ peptide, thereby limiting its aggregation. Furthermore, it was found that having rapid and sequential exchange proved detrimental as it resulted in a decreased association with Aβ. These results highlight important considerations between a balance of intermolecular interactions and ligand exchange kinetics in the design of further therapeutic candidates.