Molecular Systems Design & Engineering最新文献

α-Synuclein (αSYN), and its tendency to self-aggregate, plays an important role in the development of Parkinson's disease (PD). αSYN aggregates are characterized by a stacking of αSYN chains and an interaction between the stackings to form dimer-like structures. The stability of these supramolecular assemblies is ensured by the presence of numerous residues that adopt “β-strand” and then “β-sheet” conformations, implying multiple interactions within and between the chains of αSYN. Following our previous study on the ability of small organic molecules to form columnar supramolecular assemblies (organic nanotubes, ONs) [Le Bras, L.; Dory, Y. L.; Champagne, B. Computational prediction of the supramolecular self-assembling properties of organic molecules: the role of conformational flexibility of amide moieties. Phys. Chem. Chem. Phys., 2021, 23, 20453–20465], we propose here to unravel the ability of these ONs to interact with αSYN aggregates. More than an interaction, we expect the organic molecules to avoid the complete aggregation process and ideally to induce destabilization of the stacking. Both molecular dynamics simulation and quantum mechanical-based calculations are used to identify the key parameters of the interaction and the resulting (de)stabilization of the assembly.

Bulk radical copolymerisation of N-vinylcaprolactam (VCL) and N-vinylimidazole (VI) is studied experimentally and theoretically. It is shown that the copolymer composition is maintained up to high comonomer conversions. This is explained by a constant ratio of concentrations of comonomers in the reaction zone. The copolymers obtained show thermally induced conformational behaviour. In an aqueous medium above 60 °C, they can form compact globular structures with a hydrophobic core of VCL monomer units covered by a hydrophilic corona of VI monomer units, which allows them to be considered as a basis for thermally switchable functional nanostructures.

Aptamers are short single-stranded oligonucleotides, which offer several advantages over antibodies as bioreceptors. The widely used method for generating aptamer sequences, SELEX, has some limitations such as a limited oligonucleotide library used and amplification bias of PCR. Bioinformatics approaches have been shown to optimise and increase aptamer affinity. This research aimed to enhance the affinity of the NT-proBNP (N-terminal pro-brain natriuretic peptide, a biomarker for heart failure)-targeting aptamer acquired from SELEX using computational strategies involving sequence truncation and secondary structure-guided random mutations. DNA aptamers and protein structures are predicted by MC-Fold + 3dDNA and Robetta, respectively, whereas the computational evaluations utilize molecular docking, interaction profiles, and molecular dynamics simulations. The structural and energetic analysis revealed that the in silico optimised aptamer had more stable and robust interactions in binding to the NT-proBNP protein than the SELEX-obtained aptamer. Furthermore, our approach was supported and confirmed by in vitro colourimetric assay based on gold nanoparticle aggregation, evidenced by a detection limit of 0.5 ng mL⁻¹ which is lower than the SELEX-obtained aptamer (2.3 ng mL⁻¹).

ZSM-48 is a kind of high-silica zeolite with one dimensional (1D) 10-member ring (10-MR) channel structure. It is well known for its unique pore structure and acid properties, as well as exceptional catalytic performance in various reactions. However, the diffusion limitation and insufficient acid density pose significant challenges to its widespread application and promotion. This review aims to summarize the advancements in enhancing diffusivity and regulating acid properties of ZSM-48 zeolite, as well as its catalytic applications. To alleviate diffusion limitations, the construction of hierarchical ZSM-48 zeolites through post-treatment and in situ strategies is extensively summarized. Ongoing endeavors focus on determining the optimal balance between maintaining structural integrity and improving mass transfer capacity through post-treatment techniques. Concerning acid regulation, various strategies such as the use of a special organic structure directing agent (OSDA), seed-assisted synthesis, zeolite hybridization, and heteroatom doping strategies have been developed. The emphasis on acid regulation in ZSM-48 zeolite involves efforts to design or discover more cost-effective OSDAs. Additionally, researchers are exploring simpler and more economical seed-assisted synthesis routes to produce Al-rich candidates. In terms of catalytic application, extensive research has been conducted on various reactions including hydroisomerization of paraffin, isomerization of xylenes, cracking of hydrocarbons, and methanol conversion to hydrocarbons. Its distinctive catalytic performance is primarily related to the shape-selective advantage conferred by its 1D channel structure. In particular, ZSM-48 zeolite is widely regarded as the leading candidate in paraffin hydroisomerization reactions, attributed to its high proportion of multi-branched isomers in the catalytic products. The present review aims to provide a comprehensive reference for researchers dedicated to the synthesis, modification, and application of ZSM-48 zeolite.

The emerging variants of SARS-CoV-2 have raised serious concerns worldwide due to their infectivity, lethality, and unpredictability. Moreover, the ability of these variants to bypass vaccine protection and immunity has compelled the research community to design novel compounds against SARS-CoV-2. This study focuses on designing novel molecules using artificial intelligence methods for the development of new therapeutics against SARS-CoV-2. Furthermore, these molecules were validated against main protease (M^pro) using in-silico methods. In this study, we used the DeepScreening RNN-based web server to design novel molecules using potential inhibitors of M^pro from CHEMBL4495582. Screened compounds were further validated by molecular docking and molecular dynamics (MD) simulation studies. One hundred molecules were obtained and studied through molecular docking and MD simulations. Additionally, eight molecules, based on their docking scores, were also evaluated for electronic structure properties by conducting Density Functional Theory (DFT) calculations using the B3LYP method and a 6-31G basis set. A total of three compounds, namely L18, L36, and L26, showed very good binding and stability with the active site of the M^pro protein. The results of this study demonstrate that potential molecules can be designed using artificial intelligence methods for the rapid development of drug candidates against SARS-CoV-2, addressing the alarming worldwide situation of emerging deadly SARS-CoV-2 variants. We hope that our study will attract the attention of the scientific community to increase the application of artificial intelligence techniques in the drug discovery process.

Blue TADF materials demonstrate significant potential for OLED and photovoltaic applications. Nevertheless, systematic studies are essential to explore the relationship between molecular structures and luminescence properties to develop blue-TADF emitters. In this study, a series of new 24 donor–acceptor–donor (D–A–D) type molecules with different electron donors and acceptors are designed theoretically, and their photophysical properties are analyzed by using DFT and TD-DFT methods. We examined the combined impact of sulfur oxidation and the symmetric incorporation of a nitrogen heteroatom, with positional modifications (2-dipyridyl and 3-dipyridyl), within the phenyl ring of the acceptor group. The findings suggest that enhancing both the donating and accepting strength of the molecules results in an orthogonal geometry and a small ΔE_ST, accompanied by an enhanced charge-transfer (CT) character. Upon sulfur oxidation, the magnitude of SOC decreases, resulting in a reduction of ΔE_ST attributed to screening and lone pair effects. Through quantum chemical calculations, we have theoretically identified 12 promising blue TADF molecules, featuring small ΔE_ST, increased SOC magnitude, and higher RISC (∼10⁺⁰⁷ s⁻¹) rates. Overall, our current study provides a robust molecular design approach and reliable computational method for designing a blue TADF emitter.

Micro/nano-robots (MNRs) have gained attention as a rapidly developing field with significant potential in advanced therapies and futuristic solutions. These self-propelled robots offer a promising strategy to enhance monitoring, overcome diffusion limitations, and interact effectively with target factors. Research in MNRs has become highly influential, especially in addressing critical issues like cancer. The progression from passive micro- and nanomaterials to active MNRs and ultimately to intelligent MNRs has led to advancements in motion abilities, multifunctionality, adaptive responses, swarming behaviour, and communication among robots. Nanorobotics, featuring sophisticated submicron devices made from nanocomponents, holds great promise for revolutionizing the healthcare industry. This review aims to highlight recent progress in propulsion mechanisms, including chemically controlled micromotors, field control, and biohybrid approaches, which serve as power sources for various biomedical and environmental applications. These applications utilize different energy sources such as magnetic, light, auditory, electric, and chemical reactions, particularly in drug delivery systems for cancer treatment. This review also discusses the challenges and future directions in the practical implementation of smart MNRs, paving the way for their real-world applications.

We would like to take this opportunity to thank all of Molecular Systems Design & Engineering (MSDE)'s reviewers for helping to preserve quality and integrity in chemical science literature. We would also like to highlight the Outstanding Reviewers for MSDE in 2023.

Epoxy resins have been utilized across various industries due to their superior mechanical and chemical properties. However, discovering the optimal design of epoxy resins is challenging because of the large chemical space of polymer systems. In this study, we adopted a data-driven approach to develop an effective prediction system for epoxy resin. In particular, we constructed a database of 789 epoxy resins, encompassing four key properties: density, coefficient of thermal expansion, glass transition temperature, and Young's modulus, obtained through molecular dynamics simulations. We devised descriptors that effectively represent epoxy resins. Ultimately, a machine learning model was trained, successfully predicting properties with reasonable accuracy. Our predictive model is a generalized model that was verified across various types of epoxy resins, making it applicable to all kinds of epoxy and hardener combinations. This achievement enables large-scale screening over numerous polymers, accelerating the discovery process. Further, we conducted an in-depth analysis of the important features that have a high impact on the epoxy resin. This provides valuable insights into the structure–property relationship which can guide researchers in designing new epoxy resins.

We report a new synthetic concept for converting isotropic ionic molecules into thermotropic ionic liquid crystals by forming [2]rotaxane structures. Our results demonstrate the synthesis of liquid-crystalline (LC) rotaxane from an ionic axle molecule as a mesogen core, and a molecular ring as flexible tails, neither of which possess LC properties. The [2]rotaxane obtained exhibited an interdigitated smectic A phase at around 140 °C. A simple mixture of the axle and the ring, which cannot form a rotaxane structure, did not show an LC phase. A [2]rotaxane compound having a ring with shorter flexible tails did not show an LC phase, either. These comparisons revealed that the integration of the mesogen core and flexible tails of a sufficient length in one molecule via the rotaxane structure enables the emergence of LC nature. Our results prove that the rotaxane structure serves as a connection to spatially introduce flexible tails into the mesogen core, pioneering a new approach to LC molecular design.