Hasil untuk "Analytical chemistry"

Jenna C. Fromer, Alexandra D. Volkova, Connor W. Coley

Early stage drug discovery and molecular design projects often follow iterative design-make-test cycles. The selection of which compounds to synthesize from all possible candidate compounds is a complex decision inherent to these design cycles that must weigh multiple factors. We build upon the algorithmic downselection framework SPARROW that considers synthetic cost, synthetic feasibility, and compound utility, extending it to address additional critical factors related to the risk of synthesis failure, molecular diversity, and parallel chemistry capabilities. These design considerations further align algorithmic compound selection with the true complexity of this decision-making process, allowing SPARROW to capture a broader set of principles typically reliant on expert chemist intuition. The application of these formulations to an exemplary case study highlights SPARROW's ability to promote the selection of diverse batches of compounds whose syntheses are amenable to parallel chemistry.

Xiaojie Hou, Hongmei Yin, Xiaodie Qin et al.

ABSTRACT Pengqi sauce is a traditional Chinese naturally fermented aquatic product, and its unique flavor formation mechanism is closely related to microbial function. In this study, we combined metabolomics and microbiomics techniques to analyze the flavor evolution and the rules and mechanisms of bacterial flora action during the natural fermentation process of Wedelia sauce. On the basis of electronic nose, gas chromatography–mass spectrometry (GC–MS) and GC–ion mobility spectrometry (GC–IMS) techniques, nine core flavor components, including 2‐methylpyrazine, 1‐heptanol, tetrahydrothiophene, and isoamyl isobutyrate, which confer baking, fruity, and creamy aromas, were identified as key volatile components during the fermentation process. Meanwhile, the 16S rRNA sequencing technology was used for the first time to clarify the flavor profile of the Pengqi sauce fermentation system. The actual abundance changes of microorganisms in the Pengqi sauce fermentation system: Paracoccus, Nocardioides, and Marinilactibacillus, the absolute abundance of which reached 12,129, 9411, and 9113 copies/g, respectively, on Day 56, and still maintained a high level on Day 84. Orthogonal partial least squares discriminant analysis (OPLS‐DA) and Spearman correlation analyses indicated that the above genera showed very strong positive correlations (ρ > 0.9, p < 0.05) with key flavor substances such as 1‐hexanol and 2‐methylpyrazine, and their functional predictions indicated that they drove flavor formation through protein degradation, lipid oxidation, and glucose metabolism pathways. This study demonstrated that the absolute microbial quantification strategy can reveal the contribution of bacterial flora to fermentation flavor more accurately and provide a theoretical basis for process optimization and standardized production of traditional fermented foods.

S. Irem Kaya, Ahmet Cetinkaya, Sibel A. Ozkan

Ke Zhang

Planets are formed inside disks around young stars. The gas, dust, and ice in these natal disks are the building materials of planets, and therefore their compositions fundamentally shape the final chemical compositions of planets. In this review, we summarize current observations of molecular lines in protoplanetary disks, from near-infrared to millimeter wavelengths. We discuss the basic types of chemical reactions in disks and the current development of chemical modeling. In particular, we highlight the progress made in understanding snowline locations, abundances of main carriers of carbon, oxygen, and nitrogen, and complex organic molecules in disks. Finally, we discuss efforts to trace planet formation history by combining the understanding of disk chemistry and planet formation processes.

G. Esplugues, M. Rodríguez-Baras, D. Navarro-Almaida et al.

The observational detection of some metastable isomers in the interstellar medium with abundances comparable to those of the most stable isomer, or even when the stable isomer is not detected, highlights the importance of non-equilibrium chemistry. This challenges our understanding of the interstellar chemistry. We present a chemical study of isomers through the sulphur isomer pair HNCS and HSCN, since HSCN has been observed in regions where its stable isomer has not been detected, and the observed HNCS/HSCN ratio seems to significantly vary from cold to warm regions. We have used the Nautilus chemical code to model the formation and destruction paths of HNCS and HSCN in different astrochemical scenarios, and the time evolution of the HNCS/HSCN ratio. We have also analysed the influence of the environmental conditions on their chemical abundances. We present an observational detection of the metastable isomer HSCN in the Class I object B1-a, but not of the stable isomer HNCS, despite HNCS lying 3200 K lower in energy than HSCN. Our results show an HNCS/HSCN ratio sensitive to the gas temperature and the evolutionary time, with the highest values obtained at early stages (t<10^4 yr) and low (Tg<20 K) temperatures. The results suggest a different efficiency of the isomerisation processes depending on the source temperature. The progressive decrease of HNCS/HSCN with gas temperature at early evolutionary times indicates that this ratio may be used as a tracer of cold young objects. This work also demonstrates the key role of grain surface chemistry in the formation of the isomer pair HNCS and HSCN in cold regions, and the importance of the ions H2NCS+ and HNCSH+ in warm/hot regions. Since most of the interstellar regions where HSCN is detected are cold regions, a larger sample including sources characterised by high temperatures are needed to corroborate the theoretical results.

William Dawson, Katsuhisa Ozaki, Jens Domke et al.

The abundant demand for deep learning compute resources has created a renaissance in low precision hardware. Going forward, it will be essential for simulation software to run on this new generation of machines without sacrificing scientific fidelity. In this paper, we examine the precision requirements of a representative kernel from quantum chemistry calculations: calculation of the single particle density matrix from a given mean field Hamiltonian (i.e. Hartree-Fock or Density Functional Theory) represented in an LCAO basis. We find that double precision affords an unnecessarily high level of precision, leading to optimization opportunities. We show how an approximation built from an error-free matrix multiplication transformation can be used to potentially accelerate this kernel on future hardware. Our results provide a road map for adapting quantum chemistry software for the next generation of High Performance Computing platforms.

Jihua Chen, Yue Yuan, Amir Koushyar Ziabari et al.

Artificial Intelligence (AI) approaches are increasingly being applied to more and more domains of Science, Engineering, Chemistry, and Industries to not only improve efficiencies and enhance productivity, but also enable new capabilities. The new opportunities range from automated molecule design and screening, properties prediction, gaining insights of chemical reactions, to computer-aided design, predictive maintenance of systems, robotics, and autonomous vehicles. This review focuses on the new applications of AI in manufacturing and healthcare. For the Manufacturing Industries, we focus on AI and algorithms for (1) Battery, (2) Flow Chemistry, (3) Additive Manufacturing, (4) Sensors, and (5) Machine Vision. For Healthcare applications, we focus on: (1) Medical Vision (2) Diagnosis, (3) Protein Design, and (4) Drug Discovery. In the end, related topics are discussed, including physics integrated machine learning, model explainability, security, and governance during model deployment.

Sima Singh, Ada Raucci, Wanda Cimmino et al.

Small interfering RNA (siRNA) is essential for the process of gene silencing, especially for cancer. Despite its considerable promise, siRNA faces challenges due to stability issues of formulation and undesirable off-target side effects. In order to address these difficulties, it is essential to carefully monitor the levels of siRNA. The existing point-of-care (POC) systems cannot precisely and efficiently detect or monitor siRNA levels. In light of these challenges, this review gives the prospects of siRNA detection by proposing a novel hypothesis of existing electrical and optical-based detection of DNA/RNA with the POC platform. This hypothesis offers an interesting novel perspective to potentially fill the existing gaps, in detecting siRNA. By utilising these technologies, there is high potential to develop a proof-of-concept system that will not only overcome the existing challenges, but it will also allow effective and precise monitoring of siRNA, in real-world healthcare environments. In summary, the prospects for siRNA in the realm of POC platforms are quite encouraging, since it allows precise and effective monitoring.

Hind Yassmine Chennai, Salah Belaidi, Lotfi Bourougaa et al.

Huperzine A (HUP) plays a crucial role in Alzheimer’s therapy by enhancing cognitive function through increased cholinergic activity as a reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen in AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for Alzheimer’s disease. To achieve the goal of the discovery of potential HUP analogues with improved physicochemical properties, less toxic properties, and high biological activity, many in silico methods were applied. Based on the acetylcholinesterase–ligand complex, an e-pharmacophore model was developed. Subsequently, a virtual screening involving a collection of 1762 natural compounds, sourced from the PubChem database, was performed. This screening yielded 131 compounds that exhibited compatibility with the established pharmacophoric hypothesis. These selected ligands were then subjected to molecular docking within the active site of the 4EY5 receptor. As a result, we identified four compounds that displayed remarkable docking scores and exhibited low free binding energy to the target. These top four compounds, CID_162895946, CID_44461278, CID_44285285, and CID_81108419, were submitted to ADMET prediction and molecular dynamic simulations, yielding encouraging findings in terms of their pharmacokinetic characteristics and stability. Finally, the molecular dynamic simulation, cross-dynamic correlation matrix, free energy landscape, and MM-PBSA calculations demonstrated that two ligands from the selected ligands formed very resilient complexes with the enzyme acetylcholinesterase, with significant binding affinity. Therefore, these two compounds are recommended for further experimental research as possible (AChE) inhibitors.

Rafal Sitko, Beata Zawisza, Ewa Malicka

Honghui Shang, Yi Fan, Li Shen et al.

Quantum computing is moving beyond its early stage and seeking for commercial applications in chemical and biomedical sciences. In the current noisy intermediate-scale quantum computing era, quantum resource is too scarce to support these explorations. Therefore, it is valuable to emulate quantum computing on classical computers for developing quantum algorithms and validating quantum hardware. However, existing simulators mostly suffer from the memory bottleneck so developing the approaches for large-scale quantum chemistry calculations remains challenging. Here we demonstrate a high-performance and massively parallel variational quantum eigensolver (VQE) simulator based on matrix product states, combined with embedding theory for solving large-scale quantum computing emulation for quantum chemistry on HPC platforms. We apply this method to study the torsional barrier of ethane and the quantification of the protein-ligand interactions. Our largest simulation reaches $1000$ qubits, and a performance of $216.9$ PFLOPS is achieved on a new Sunway supercomputer, which sets the state-of-the-art for quantum computing emulation for quantum chemistry

S. A. Deshmukh, H. -G. Ludwig

Binary molecules such as CO, OH, CH, CN, and C$_2$ are often used as abundance indicators in stars. These species are usually assumed to be formed in chemical equilibrium. The time-dependent effects of hydrodynamics can affect the formation and dissociation of these species and may lead to deviations from chemical equilibrium. We aim to model departures from chemical equilibrium in dwarf stellar atmospheres by considering time-dependent chemical kinetics alongside hydrodynamics and radiation transfer. We examine the effects of a decreasing metallicity and an altered C/O ratio on the chemistry when compared to the equilibrium state. We used the radiation-(magneto)hydrodynamics code CO5BOLD, and its own chemical solver to solve for the chemistry of 15 species and 83 reactions. The species were treated as passive tracers and were advected by the velocity field. The steady-state chemistry was also computed to isolate the effects of hydrodynamics. In most of the photospheres in the models we present, the mean deviations are smaller than $0.2$ dex, and they generally appear above $\logτ = -2$. The deviations increase with height because the chemical timescales become longer with decreasing density and temperature. A reduced metallicity similarly results in longer chemical timescales and in a reduction in yield that is proportional to the drop in metallicity; a decrease by a factor $100$ in metallicity loosely corresponds to an increase by factor $100$ in chemical timescales. As both CH and OH are formed along reaction pathways to CO, the C/O ratio means that the more abundant element gives faster timescales to the constituent molecular species. Overall, the carbon enhancement phenomenon seen in very metal-poor stars is not a result of an improper treatment of molecular chemistry for stars up to a metallicity as low as [Fe/H] = $-3.0$.

Shaohua Lu, Hong Lu, Tingkai Zheng et al.

Abstract The development of high-throughput omics technology has greatly promoted the development of biomedicine. However, the poor reproducibility of omics techniques limits their application. It is necessary to use standard reference materials of complex RNAs or proteins to test and calibrate the accuracy and reproducibility of omics workflows. The transcriptome and proteome of most cell lines shift during culturing, which limits their applicability as standard samples. In this study, we demonstrated that the human hepatocellular cell line MHCC97H has a very stable transcriptome (r = 0.983~0.997) and proteome (r = 0.966~0.988 for data-dependent acquisition, r = 0.970~0.994 for data-independent acquisition) after 9 subculturing generations, which allows this steady standard sample to be consistently produced on an industrial scale in long term. Moreover, this stability was maintained across labs and platforms. In sum, our study provides omics standard reference material and reference datasets for transcriptomic and proteomics research. This helps to further standardize the workflow and data quality of omics techniques and thus promotes the application of omics technology in precision medicine.

Paweł Kościelniak

Eric Cancès, Geneviève Dusson, Gaspard Kemlin et al.

In this article, we propose general criteria to construct optimal atomic centered basis sets in quantum chemistry. We focus in particular on two criteria, one based on the ground-state one-body density matrix of the system and the other based on the ground-state energy. The performance of these two criteria are then numerically tested and compared on a parametrized eigenvalue problem, which corresponds to a one-dimensional toy version of the ground-state dissociation of a diatomic molecule.

Gargee Roy, Ritu Gupta, Satya Ranjan Sahoo et al.

Ferrocene, since its discovery in 1951, has been extensively exploited as a redox probe in a variety of processes ranging from solution chemistry, medicinal chemistry, supramolecular chemistry, surface chemistry to solid-state molecular electronic and spintronic circuit elements to unravel electrochemical charge-transfer dynamics. Ferrocene represents an extremely chemically and thermally stable, and highly reproducible redox probe that undergoes reversible one-electron oxidation and reduction occurring at the interfaces of electrode/ferrocene solution in response to applied anodic and cathodic potentials, respectively. It has been almost 70 years after its discovery and has become one of the most widely studied and model organometallic compounds not only for probing electrochemical charge-transfer process but also as molecular building blocks for the synthesis of chiral organometallic catalysts, potential drug candidates, polymeric compounds, electrochemical sensors, to name a few. Ferrocene and its derivatives have been a breakthrough in many aspects due to its versatile reactivity, fascinating chemical structures, unconventional metal-ligand coordination, and the magic number of electrons (18 e-). The present review discusses the recent progress made towards ferrocene-containing molecular systems exploited for redox reactions, surface attachment, spin-dependent electrochemical process to probe spin polarization, photo-electrochemistry, and integration into prototype molecular electronic devices. Overall, the present reviews demonstrate a piece of collective information about the recent advancements made towards the ferrocene and its derivatives that have been utilized as iconic redox markers.

Elena Gerasimova, Elena Gazizullina, Sofya Kolbaczkaya et al.

For the first time, new possibilities of using the DPPH^• as a signal-forming oxidant molecule with potentiometric detection are shown. The CV method confirmed the presence of a quasi-reversible potential-determining system DPPH^•/DPPH-H under experimental conditions. This fact makes it possible to use DPPH^• as the model of the oxidizing agent for obtaining an analytical signal by the potentiometry method. The potentiometric approach makes it possible to obtain the value of the Nernst slope and the antioxidant capacity in one experiment. It consists of an antioxidant supplement and two consecutive DPPH^• supplements. In this case, the calculation of the Nernst slope is carried out by introducing the second addition of the oxidizing agent and constructing a calibration curve against the reaction background with an antioxidant. Solutions of individual antioxidants α-tocopherol, quercetin, (±)-catechin hydrate, and α-lipoic acid were studied by the developed approach. A high correlation with the results of spectrophotometric measurements is shown. At the same time, the potentiometry method is devoid of the concentration limitations of the spectrophotometric method, which was confirmed. In the study of plant materials extracts, a high correlation of antioxidant capacity, obtained by potentiometric and spectrophotometric methods, was shown only for objects whose color did not contribute to the DPPH^• absorption. The versatility of the potentiometric method for studying objects of any color was shown.

H. E. O'Hora, S. V. Petersen, J. Vellekoop et al.

<p>Paleotemperature reconstructions of the end-Cretaceous interval document local and global climate trends, some driven by greenhouse gas emissions from Deccan Traps volcanism and associated feedbacks. Here, we present a new clumped-isotope-based paleotemperature record derived from fossil bivalves from the Maastrichtian type region in southeastern Netherlands and northeastern Belgium. Clumped isotope data document a mean temperature of <span class="inline-formula">20.4±3.8</span> <span class="inline-formula">^∘</span>C, consistent with other Maastrichtian temperature estimates, and an average seawater <span class="inline-formula"><i>δ</i>¹⁸</span>O value of <span class="inline-formula">0.2±0.8 ‰</span> VSMOW for the region during the latest Cretaceous (67.1–66.0 Ma). A notable temperature increase at <span class="inline-formula">∼66.4</span> Ma is interpreted to be a regional manifestation of the globally defined Late Maastrichtian Warming Event, linking Deccan Traps volcanic CO<span class="inline-formula">₂</span> emissions to climate change in the Maastricht region. Fluctuating seawater <span class="inline-formula"><i>δ</i>¹⁸</span>O values coinciding with temperature changes suggest alternating influences of warm, salty southern-sourced waters and cooler, fresher northern-sourced waters from the Arctic Ocean. This new paleotemperature record contributes to the understanding of regional and global climate response to large-scale volcanism and ocean circulation changes leading up to a catastrophic mass extinction.</p>

Zhenlong Yu, Jian Gao, Xiaolei Zhang et al.

Abstract NEMO/IKKβ complex is a central regulator of NF-κB signaling pathway, its dissociation has been considered to be an attractive therapeutic target. Herein, using a combined strategy of molecular pharmacological phenotyping, proteomics and bioinformatics analysis, Shikonin (SHK) is identified as a potential inhibitor of the IKKβ/NEMO complex. It destabilizes IKKβ/NEMO complex with IC50 of 174 nM, thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo. In addition, we also elucidated the potential target sites of SHK in the NEMO/IKKβ complex. Our study provides some new insights for the development of potent small-molecule PPI inhibitors.