RSC Mechanochemistry最新文献

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Piezoelectric biomaterials have diverse potential biomedical applications via ultrasound-based wireless mechanochemical reaction at a remote area of the body/medical device. However, most biomaterials have weak piezoelectric properties compared to chemically designed piezoelectric materials. In the current approach, piezoelectric properties of certain biomaterials are enhanced by transforming them into anisotropic fibril/sheet-like morphology. Here, we demonstrate that the piezoelectric property of amyloid fibrils can be enhanced by 2 times via conjugation with nanoparticles and this can enhance the ultrasound-based mechanochemical production of reactive oxygen species by 4 times. In particular, we have synthesized nanoparticle-conjugated lysozyme fibrils with a piezoelectric constant value as high as 82 pm V⁻¹. Thin films derived from these materials can generate periodic voltage/current pulses under the exposure of medical-grade ultrasound that can reach up to 1 V/15 nA. A colloidal dispersion of these materials generates superoxide/hydroxyl radicals via ultrasound-based mechanochemical reaction and degrade a dye. This strategy can be adapted to improve the mechanochemical reaction performance of weakly piezoelectric materials.

We report a continuous, solvent-free method for aldimine synthesis using single-screw extrusion (SSE) that achieves high yields with water as the sole byproduct. Under optimized conditions, SSE delivered aldimines in high to near-quantitative yields (>99% for selected derivatives) across diverse substrate classes including cyclohexanol amines, L-phenylalaninate methyl esters and ethylenediamine-derived bis-aldimines without requiring product purification. Furthermore, an optimized process is demonstrated, with a throughput rate of 6740 g day⁻¹, corresponding to a space-time yield of 1716 kg m⁻³ day⁻¹. The extrusion process outperformed mechanochemical grinding and batch methods in efficiency and crystallinity, as evidenced by the DSC endothermic peak. The synthesized compounds were characterized using various analytical tools like IR, GC-MS, NMR, single crystal XRD and HRMS. By leveraging mechanochemistry in a continuous flow system, SSE provides a simple yet powerful platform that significantly expands the possibilities for sustainable organic synthesis.

Quantitative analysis of crude reaction mixtures is essential for the development of new synthetic methodologies and conducting mechanistic studies. While internal standard method is widely used for determining reaction yields in homogeneous solvent-based organic synthesis, its application in mechanochemical synthesis, which often involves heterogeneous mixtures, has not been properly validated. This study showcases applicability of triphenylmethane (TPM) as a solid internal standard in liquid-assisted, multi-component synthesis of homomeric cycHC[8] and mono-biotinylated mixHC[8] eight-membered cyclohexanohemicucurbit[n]urils. A fast and reliable HPLC-UV-MS analytical procedure was developed to determine yields by analyzing crude reaction mixtures, as a prerequisite of applying design-of-experiments optimisation approach. The influence of various parameters, including TPM concentration, reactant mixture weight, milling time, and the type and amount of liquid-assisted grinding additive, on the validity of the analysis was systematically studied. The results indicate that the primary challenge to trustworthy analysis arises from the non-uniform distribution of components. However, this issue can be detected with proper sampling and mitigated by optimising parameters to ensure uniform distribution of the internal standard throughout the reaction mixture. The results could be valuable for ensuring the credibility of ex situ and in situ analytical methods used to track the progress of mechanochemical reactions through single-point measurements.

Solvents have long been integral to the success of synthetic chemistry, influencing reaction rates, mechanisms, and product selectivity. However, mechanochemistry—typically involving the grinding and mixing of solid reagents—offers an alternative environment that is solvent-free or at least greatly minimizes solvent use, and that drives reactions through mechanical force. In a recent study, the reaction between the salt of a bulky allyl anion, K[A′] (A′ = 1,3-(SiMe₃)₂C₃H₃), and a nickel halide gave very different outcomes depending on whether the reaction was conducted without solvent using a solid material, with a starting solvated complex, [Ni(py)₄Cl₂], modified by a small amount of pyridine, or in pyridine solution. Under certain conditions, halide metathesis occurred, forming the allyl complex in near quantitative yield. Under others, a redox reaction dominated, generating allyl radicals that coupled and left {A′}₂ (1,3,4,6-tetrakis(trimethylsilyl)hexa-1,5-diene) as the major product. To understand these differing outcomes, the formation mechanisms of under varying solvent conditions were investigated here using Density Functional Theory (DFT). The effects of the reaction conditions on factors such as Gibbs free energy change, bond energy behavior, and transition states collectively suggest that electrostatic stabilization dominates in the solvent phase. In the case of solvate-assisted conditions, a complete energy profile diagram of the reaction between [Ni(py)₄Cl₂] and 2K[A′], leading to and KCl, was calculated, with evidence for one of the intermediates ([A′Ni(py)Cl]) being provided by experiments. Calculations confirm that coordination of pyridine to the nickel, whether from the free liquid or (preferentially) from the pyridine solvate, weakens the Ni–Cl bond so that metathesis can proceed easily. If pyridine is absent (i.e., under solvent-free conditions), the redox route will have a kinetic advantage in the reaction. This study provides molecular-level insights for understanding and optimizing solvent-assisted grinding processes.

The co-crystal formed from the WHO essential drug rac-ibuprofen (IBU) and the food additive nicotinamide (NIC) exhibits enhanced physicochemical and analgesic properties compared to the pure active pharmaceutical ingredient (API), exemplifying how co-crystallization can modify pharmaceutical characteristics. Herein, we present a more sustainable, solvent-free mechanochemical process for synthesizing rac-ibuprofen:nicotinamide (IBU:NIC) co-crystals, moving beyond conventional solution-based methods that typically require substantial amounts of solvents and energy. For the first time, we investigate the application of a horizontal attritor mill for co-crystal synthesis. Our findings demonstrate the effectiveness of this milling technology in facilitating the co-crystallization process, achieving pure co-crystals within 30 min. Additionally, initial experiments were conducted to explore the transition from a batch process to a sequential process. While our approach demonstrate the use of attritor mills for pharmaceutical co-crystal synthesis on a multigram scale, it also indicates opportunities for scaling up this process using industrial attritor mills. This work underscores the adaptation of existing grinding technologies to facilitate mechanochemical reactions, showcasing greener alternatives for pharmaceutical manufacturing.

Ultrasonic industrial applications require theoretical support and practical guidance from a comprehensive understanding of sonochemical reaction dynamics. The influence of acoustic factors (frequency and pressure amplitude) and external parameters (liquid height) on sonochemical activity were researched. The phenomenon of sonoluminescence (SL), sonochemiluminescence (SCL) and potassium iodide (KI) dosimetry were investigated at 114 different settings. The settings included electrical loading-power of 10, 20, 30, and 40 W, 10 frequencies ranging from 22 to 2000 kHz, and reactor volumes of 200, 300, and 400 ml. A new area selection image processing technique was used to conduct a systematically quantitative analysis of SL and SCL across a broader frequency range. The sonochemical activity could be categorised into three zones based on the ultrasonic frequency (22 to 2000 kHz): f < 200 kHz, 200 kHz ≤ f ≤ 1000, and 1000 kHz ≤ f ≤ 2000 kHz. The Pearson and Spearman correlation coefficients were used to discuss the correlation between SL, SCL, reactive oxidant species (ROS) and hydrogen peroxide yields. The findings indicate that the influence of liquid height on cavitation activity within the reactor is mostly manifested in the power density. The ultrasonic oxidation capacity (as indicated by the yield of ROS) exhibits a strong positive relationship with SL intensity. A divergence of correlation between SL and I₃⁻ yield was observed. There was a lack of correlation between sonochemical activities (e.g. SCL and ROS yield). The poor correlation highlighted the importance of considering chemical mechanisms and reaction locations concerning the collapsing bubble.

By using in situ Raman spectroscopy for reaction monitoring, we compare ball milling (BM) and resonant acoustic mixing (RAM) in the preparation α,β-unsaturated ketones (chalcones). RAM achieves similar transformations to BM, though adjustments in reaction conditions may be necessary due to different mixing regimes.

Organic solvents are ubiquitously used in synthetic coordination chemistry, but these solution-based synthetic methods have severe drawbacks, such as the incapability of isolating highly reactive species which react with the solvent molecules, less-controllable heterogeneous reactions when using insoluble substrate(s), and unfavourable solvent molecule coordination. In recent years, coordination chemists have started employing mechanochemical methods (e.g., ball mill) to overcome these drawbacks. Herein, we offer our perspective about how mechanochemical methods have enabled coordination chemists to achieve what would otherwise be impossible. It should be noted that, this perspective should not be treated as a comprehensive review of mechanochemistry in coordination chemistry, instead, a “stepping stone” aiming at inspiring further endeavours. Also, due to the research background of the authors, the selection of examples herein may appear biased towards main-group chemistry, which we feel necessary to remind our readers.

Mechanochemistry can be an essential tool for coordination chemistry, demonstrating significant advantages over solution protocols, enabling highly selective, efficient, and rapid syntheses with conversion of the reagents achieved within minutes of grinding. The mechanochemical synthesis of heteroleptic Zn(II) and Cu(II) complexes containing non-chelating ligands like pyridine and p-halogen-substituted benzoates showcased the potential of this technique, with a detailed comparison to solution-based synthetic methods. Structural analyses via X-ray diffraction confirm that the crystalline phases produced mechanochemically are identical to those obtained in solution. The synthesis of anhydrous complexes under dry mechanochemical conditions was also achieved without specialized equipment, highlighting the versatility of this approach even for moisture-sensitive compounds.