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Crystal structure determination of Verinurad via proton-detected ultra-fast MAS NMR and machine learning 通过质子检测超快 MAS NMR 和机器学习确定 Verinurad 的晶体结构
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-17 DOI: 10.1039/d4fd00076e
Daria Torodii, Jacob Holmes, Pinelopi Moutzouri, Sten O. Nilsson Lill, Manuel Cordova, Arthur C. Pinon, Kristof Grohe, Sebastian Wegner, Okky Dwichandra Putra, Stefan Tommy Norberg, Anette Welinder, Staffan Schantz, Lyndon Emsley
The recent development of ultra-fast MAS (>100 kHz) provides new opportunities for structural characterization in solids. Here we use NMR crystallography to validate the structure of verinurad, a microcrystalline active pharmaceutical ingredient. To do this, we take advantage of 1H resolution improvement at ultra-fast MAS and use solely 1H-detected experiments and machine learning methods to assign all the experimental proton and carbon chemical shifts. This framework provides a new tool for elucidating chemical information from crystalline samples with limited sample volume and yields remarkably faster acquisition times compared to 13C-detected experiments, without the need to employ dynamic nuclear polarization.
超快速 MAS(100 kHz)的最新发展为固体结构表征提供了新的机遇。在此,我们利用核磁共振晶体学验证了微晶活性药物成分 verinurad 的结构。为此,我们利用超快 MAS 的 1H 分辨率改进,并完全使用 1H 检测实验和机器学习方法来分配所有实验质子和碳化学位移。这一框架为从样品体积有限的晶体样品中阐明化学信息提供了新的工具,与 13C 检测实验相比,采集时间大大缩短,而且无需使用动态核偏振。
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引用次数: 0
Atomic-level structure of the amorphous drug Atuliflapon by NMR crystallography 通过核磁共振晶体学研究无定形药物阿托利夫拉朋的原子级结构
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-17 DOI: 10.1039/d4fd00078a
Jacob Holmes, Daria Torodii, Martins Balodis, Manuel Cordova, Albert Hofstetter, Federico Paruzzo, Sten O. Nilsson Lill, Emma Eriksson, Pierrick Berruyer, Bruno Simões de Almeida, Michael J. Quayle, Stefan Tommy Norberg, Anna Svensk-Ankarberg, Staffan Schantz, Lyndon Emsley
We determine the complete atomic-level structure of the amorphous form of the drug altuliflapon, a 5-lipooxygenase activating protein (FLAP) inhibitor, by chemical shift driven NMR crystallography. The ensemble of preferred structures allows us to identify a number of specific conformations and interactions that stabilize the amorphous structure. These include preferred hydrogen bonding motifs with water and with other drug molecules, as well as conformations of the cyclohexane and pyrazole rings that stabilize structure by indirectly allowing for optimization of hydrogen bonding.
我们通过化学位移驱动核磁共振晶体学确定了药物 Altuliflapon(一种 5-脂氧合酶活化蛋白(FLAP)抑制剂)无定形形式的完整原子级结构。通过优选结构的组合,我们确定了稳定无定形结构的一些特定构象和相互作用。其中包括与水和其他药物分子的首选氢键图案,以及环己烷和吡唑环的构象,这些构象通过间接优化氢键来稳定结构。
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引用次数: 0
Nanoscale visualization of the anti-tumor effect of a plasma-activated Ringer’s lactate solution 等离子激活的林格乳酸盐溶液抗肿瘤效果的纳米级可视化
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-16 DOI: 10.1039/d4fd00116h
Junichi Usuda, Kenshin Yagyu, Hiromasa Tanaka, Masaru Hori, Kenji Ishikawa, Takahashi Yasufumi
Plasma-activated Ringer’s lactate solutions (PALs), which are Ringer’s lactate solutions treated with non-thermal atmospheric-pressure plasma, have anti-tumor effect and can be used for chemotherapy. As the anti-tumor effect of the PAL is influenced by the cell-treatment time, it is necessary to monitor the structural changes of the cell surface with non-invasive, nanoscale, and time-lapse imaging to understand the anti-tumor effect. In this study, to characterize the anti-tumor effect of the PAL, we used a scanning ion conductance microscopy (SICM), using glass nanopipettes as probes, to visualize the structural changes of the cell surface. SICM time-lapse topographic imaging visualized a decrease in the movement of lamellipodia in normal cells and cancer cells after the PAL treatment. Furthermore, in normal cells, protrusive structures were observed on the cell surface. Time-lapse imaging using SICM allowed us to characterize the differences in the morphological changes between the normal and cancer cells upon exposure to the PAL.
等离子体激活的林格氏乳酸盐溶液(PALs)是用非热大气压等离子体处理过的林格氏乳酸盐溶液,具有抗肿瘤作用,可用于化疗。由于 PAL 的抗肿瘤效果受细胞处理时间的影响,因此有必要利用无创、纳米级和延时成像技术监测细胞表面的结构变化,以了解其抗肿瘤效果。在本研究中,为了表征 PAL 的抗肿瘤效果,我们使用了扫描离子电导显微镜(SICM),以玻璃纳米吸头为探针,观察细胞表面的结构变化。SICM 延时地形图成像显示,PAL 处理后,正常细胞和癌细胞中的片状突起运动均有所减少。此外,在正常细胞中,还观察到细胞表面有突起结构。利用 SICM 的延时成像技术,我们得以描述正常细胞和癌细胞在接触 PAL 后形态变化的差异。
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引用次数: 0
Embedding human knowledge in material screening pipeline as filters to identify novel synthesizable inorganic materials 将人类知识嵌入材料筛选管道,作为识别新型可合成无机材料的过滤器
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-16 DOI: 10.1039/d4fd00120f
Basita Das, Kangyu Ji, FANG SHENG, Kyle McCall, Tonio Buonassisi
How might one embed a chemist’s knowledge into an automated materials-discovery pipeline? In generative design for inorganic crystalline materials, generating candidate compounds is no longer a bottleneck — there are now synthetic datasets of millions of compounds. However, weeding out unsynthesizable or difficult to synthesize compounds remains an outstanding challenge. Post-generation “filters” have been proposed as a means of embedding human domain knowledge, either in the form of scientific laws or rules of thumb. Examples include charge neutrality, electronegativity balance, and energy above hull. Some filters are “hard” and some are “soft” — for example, it is difficult to envision creating a stable compound while violating the rule of charge neutrality; however, several compounds break the Hume-Rothery rules. It is therefore natural to wonder: Can one compile a comprehensive list of “filters” that embed domain knowledge, adopt a principled approach to classifying them as either non- conditional or conditional "filters," and envision a software environment to implement combinations of these in a systematic manner? In this commentary we explore such questions, “filters” for screening of novel inorganic compounds for synthesizability.
如何将化学家的知识嵌入自动材料发现管道?在无机晶体材料的生成设计中,生成候选化合物已不再是瓶颈--现在已有数百万个化合物的合成数据集。然而,如何剔除无法合成或难以合成的化合物仍是一项艰巨的挑战。有人提出了后代 "过滤器",以科学定律或经验法则的形式嵌入人类领域知识。这方面的例子包括电荷中性、电负性平衡和高于船体的能量。有些过滤是 "硬 "的,有些则是 "软 "的--例如,很难设想在违反电荷中性规则的同时还能创造出稳定的化合物;然而,有几种化合物却违反了 Hume-Rothery 规则。因此,我们自然会有这样的疑问:我们能否编制一份包含领域知识的 "过滤器 "综合清单,采用一种有原则的方法将它们归类为非条件 "过滤器 "或条件 "过滤器",并设想一种软件环境,以系统的方式实现这些过滤器的组合?在本评论中,我们将探讨此类问题,即筛选新型无机化合物合成性的 "过滤器"。
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引用次数: 0
Exploring the crystallisation of aspirin in a confined porous material using solid-state nuclear magnetic resonance 利用固态核磁共振探索阿司匹林在密闭多孔材料中的结晶过程
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-16 DOI: 10.1039/d4fd00123k
Marie Juramy, Eric Besson, Stephane Gastaldi, Fabio Ziarelli, Stéphane Viel, Giulia Mollica, Pierre Thureau
In this study, nuclear magnetic resonance (NMR) is used to investigate the crystallisation behaviour of aspirin within a mesoporous SBA-15 silica material. The potential of dynamic nuclear polarisation (DNP) experiments is also investigated using specifically designed porous materials that incorporate polarising agents within their walls. The formation of the metastable crystalline form II is observed when crystallisation occurs within the pores of the mesoporous structure. Conversely, bulk crystallisation yields the most stable form, namely form I, of aspirin. Remarkably, the metastable form II remains trapped within the pores of mesoporous SBA-15 silica material even 30 days after impregnation, underscoring its persistent stability within this confined environment.
在这项研究中,核磁共振 (NMR) 被用来研究阿司匹林在介孔 SBA-15 硅材料中的结晶行为。此外,还利用专门设计的多孔材料(其壁内含有极化剂)研究了动态核极化(DNP)实验的潜力。当结晶发生在介孔结构的孔隙中时,可观察到 "可转移结晶形式 II "的形成。相反,块状结晶会产生最稳定的阿司匹林形态,即形态 I。值得注意的是,即使在浸渍 30 天后,析晶形式 II 仍被困在介孔 SBA-15 二氧化硅材料的孔隙中,这表明它在这种密闭环境中具有持久的稳定性。
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引用次数: 0
Scanning electrochemical probe microscopy: towards the characterization of micro-and nanostructured photocatalytic materials 扫描电化学探针显微镜:表征微纳米结构的光催化材料
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-15 DOI: 10.1039/d4fd00136b
Giada Caniglia, Sarah Horn, Christine Kranz
Platinum-black (Pt-B) has been demonstrated as an excellent electrocatalytic material for the electrochemical oxidation of hydrogen peroxide (H2O2). As Pt-B films can be deposited electrochemically, micro- and nano-sized conductive transducers can be modified with Pt-B. Here, we present the potential of Pt-B micro- and sub-micro-sized sensors for the detection and quantification of hydrogen (H2) in solution. Using these microsensors, no sampling step for H2 determination is required and e.g., in photocatalysis, the onset of H2 evolution can be monitored in situ. We present Pt-B- based H2 micro- and sub-micro-sized sensors based on different electrochemical transducers such as microelectrodes and atomic force microscopy (AFM)- scanning electrochemical microscopy (SECM) probes, which enable local measurements e.g., at heterogenized photocatalytically active samples. The microsensors are characterized in terms of limits of detection (LOD), which ranges from 4.0 µM to 30 µM depending on the size of the sensors and the experimental conditions such as type of electrolyte and pH. The sensors were tested for the in situ H2 evolution by light-driven water-splitting, i.e., using ascorbic acid or triethanolamine, showing a wide linear concertation range, good reproducibility, and high sensitivity. Proof-of-principle experiments using Pt-B-modified cantilever-based sensors were performed using a model sample like platinum substrate to map the electrochemical H2 evolution along with the topography using AFM-SECM.
铂黑(Pt-B)已被证明是过氧化氢(H2O2)电化学氧化的优良电催化材料。由于铂-B 薄膜可以通过电化学方法沉积,因此可以用铂-B 对微型和纳米尺寸的导电传感器进行改性。在此,我们介绍了 Pt-B 微型和亚微型传感器在检测和定量溶液中的氢(H2)方面的潜力。使用这些微型传感器,测定氢气不需要取样步骤,例如,在光催化过程中,可以原位监测氢气进化的开始。我们介绍了基于 Pt-B 的微型和亚微型 H2 传感器,这些传感器基于不同的电化学传感器,例如微电极和原子力显微镜(AFM)- 扫描电化学显微镜(SECM)探针,可对异质化光催化活性样品等进行局部测量。根据传感器的尺寸和实验条件(如电解质类型和 pH 值),微型传感器的检测限(LOD)从 4.0 µM 到 30 µM。该传感器通过光驱动分水(即使用抗坏血酸或三乙醇胺)进行了原位 H2 演化测试,结果显示其线性协调范围宽、重现性好、灵敏度高。使用 Pt-B 改性悬臂式传感器进行了原理验证实验,使用类似铂基底的模型样品,利用原子力显微镜-扫描电子显微镜绘制了电化学 H2 演化和形貌图。
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引用次数: 0
Indigo production identifies hotspots in cytochrome P450 BM3 for diversifying aromatic hydroxylation. 靛蓝生产确定了细胞色素 P450 BM3 中芳香烃羟化多样化的热点。
IF 3.3 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-12 DOI: 10.1039/d4fd00017j
Douglas J Fansher, Jonathan N Besna, Joelle N Pelletier

Evolution of P450 BM3 is a topic of extensive research, but screening the various substrate/reaction combinations remains a time-consuming process. Indigo production has the potential to serve as a simple high-throughput method for reaction screening, as bacterial colonies expressing indigo (+) variants can be visually identified via their blue phenotype. Indigo (+) single variants, indigo (-) single variants and a combinatorial library, containing mutations that enable the blue phenotype, were screened for their ability to hydroxylate a panel of 12 aromatic compounds using the 4-aminoantipyrine colorimetric assay. Recombination of indigo (+) single variants to create a multiple-variant library is a particularly useful strategy, as all top performing P450 BM3 variants with high hydroxylation activity were either indigo (+) single variants or contained multiple substitutions. Furthermore, active variants, as determined using the 4-AAP assay, were further characterized and several variants were identified that gave more than 90% conversion with 1,3-dichlorobenzene and predominantly formed 2,6-dichlorophenol; other variants showed significant substrate selectivity. This supports the hypothesis that substitution at positions that enable the indigo (+) phenotype, or hotspot residues, is a general mechanism for increasing aromatic hydroxylation activity. Overall, this research demonstrates that indigo (+) single variants, identified via colorimetric colony-based screening, may be recombined to generate a multiply-substituted variant library containing many variants with high aromatic hydroxylation activity. The combination of colony-based screening and other screening assays greatly accelerates enzyme engineering, as readily-identified indigo (+) single variants can be recombined to create a library of active multiple variants without extensive screening of single variants.

P450 BM3 的进化是一个广泛的研究课题,但筛选各种底物/反应组合仍然是一个耗时的过程。靛蓝的产生有可能成为一种简单的高通量反应筛选方法,因为表达靛蓝(+)变体的细菌菌落可以通过其蓝色表型直观地识别出来。使用 4-氨基安替比林比色法筛选了靛蓝(+)单一变体、靛蓝(-)单一变体和组合库(其中包含可产生蓝色表型的突变)羟化 12 种芳香族化合物的能力。重组靛蓝(+)单变体以创建多变体库是一种特别有用的策略,因为所有具有高羟化活性的 P450 BM3 顶级变体要么是靛蓝(+)单变体,要么包含多个取代。此外,利用 4-AAP 分析法确定的活性变体得到了进一步表征,并确定了几个变体,这些变体与 1,3-二氯苯的转化率超过 90%,并主要形成 2,6-二氯苯酚;其他变体则表现出明显的底物选择性。这支持了一种假设,即在能够产生靛蓝(+)表型的位置或热点残基上进行取代是提高芳香烃羟基化活性的一般机制。总之,这项研究表明,通过比色菌落筛选鉴定出的靛蓝(+)单一变体可以通过重组产生一个多取代变体库,其中包含许多具有高芳香羟化活性的变体。基于菌落的筛选与其他筛选测定法的结合大大加快了酶工程的进程,因为无需对单一变体进行广泛筛选,就可以将容易识别的靛蓝(+)单一变体进行重组,生成具有活性的多重变体库。
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引用次数: 0
Quantum chemistry, classical heuristics, and quantum advantage 量子化学、经典启发法和量子优势
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-11 DOI: 10.1039/d4fd00141a
Garnet Kin-Lic Chan
We describe the problems of quantum chemistry, the intuition behind classical heuristic methods used to solve them, a conjectured form of the classical com- plexity of quantum chemistry problems, and the subsequent opportunities for quantum advantage. This article is written for both quantum chemists and quan- tum information theorists. In particular, we attempt to summarize the domain of quantum chemistry problems as well as the chemical intuition that is applied to solve them within concrete statements (such as a classical heuristic cost conjec- ture) in the hope that this may stimulate future analysis.
我们描述了量子化学问题、用于解决这些问题的经典启发式方法背后的直觉、量子化学问题经典复杂性的猜想形式,以及量子优势的后续机遇。本文既面向量子化学家,也面向量子信息理论家。特别是,我们试图总结量子化学问题的领域,以及在具体陈述(如经典启发式成本组合)中用于解决这些问题的化学直觉,希望这能激发未来的分析。
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引用次数: 0
Concluding remarks: reflections on the Faraday Discussion on New Directions in Molecular Scattering 结束语:对法拉第分子散射新方向讨论的思考
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-11 DOI: 10.1039/d4fd00118d
Mark Brouard
These concluding remarks summarize the Faraday Discussion on New Directions in Molecular Scattering [citation]. The Discussion brought together scientists from a wide range of disciplines, from astrochemistry to coherent quantum control, and the submitted papers highlighted the need for innovation in experimental methods and computational tools to tackle more complex systems, relevant to chemistry in the real world. As recorded in the previous pages of this Discussion, the meeting saw lively debate on numerous topical issues. This summary outlines some of the highlighted key developments in the field, and points towards future directions of molecular scattering research.
这些结束语总结了法拉第分子散射新方向讨论[引文]。本次讨论汇聚了从天体化学到相干量子控制等众多学科的科学家,提交的论文强调了实验方法和计算工具创新的必要性,以解决现实世界中与化学相关的更复杂的系统问题。正如本讨论前几页所记录的那样,会议就众多热点问题展开了热烈讨论。本摘要概述了该领域的一些重要发展,并指出了分子散射研究的未来方向。
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引用次数: 0
How big is Big Data? 大数据有多大?
IF 3.4 3区 化学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-07-11 DOI: 10.1039/d4fd00102h
Daniel Speckhard, Tim Bechtel, Luca M. Ghiringhelli, Martin Kuban, Santiago Rigamonti, Claudia Draxl
Big data has ushered in a new wave of predictive power using machine learning models. In this work, we assess what {it big} means in the context of typical materials-science machine-learning problems. This concerns not only data volume, but also data quality and veracity as much as infrastructure issues. With selected examples, we ask (i) how models generalize to similar datasets, (ii) how high-quality datasets can be gathered from heterogenous sources, (iii) how the feature set and complexity of a model can affect expressivity, and (iv) what infrastructure requirements are needed to create larger datasets and train models on them. In sum, we find that big data present unique challenges along very different aspects that should serve to motivate further work.
大数据带来了使用机器学习模型进行预测的新浪潮。在这项工作中,我们将评估{it big}在典型材料科学机器学习问题中的含义。这不仅涉及数据量,还涉及数据质量和真实性以及基础设施问题。通过选定的例子,我们提出了以下问题:(i) 模型如何泛化到类似的数据集;(ii) 如何从不同来源收集高质量的数据集;(iii) 模型的特征集和复杂性如何影响表达能力;(iv) 创建更大的数据集并在其上训练模型需要哪些基础设施要求。总之,我们发现大数据在不同方面提出了独特的挑战,这些挑战应有助于推动进一步的工作。
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引用次数: 0
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Faraday Discussions
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