Pub Date : 2024-09-18DOI: 10.26434/chemrxiv-2024-jg6bn
Vivian S., Lin, Aaron T., Wright, Stephen J., Callister, Leo J., Gorham, Gerard X., Lomas, Agne, Sveistyte, John T., Melchior, Priscila M., Lalli, Chathuri J., Kombala, Tong, Zhang, Vanessa L., Paurus
Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses chemical probes to label active enzymes selectively and covalently in complex proteomes. Competitive ABPP, which involves treatment of the active proteome with an analyte of interest, is especially powerful for profiling how small molecules impact specific protein activities. Advances in higher throughput workflows have made it possible to generate extensive competitive ABPP data across various biological systems and treatments, making this approach highly appealing for characterizing shared and unique proteins affected by perturbations such as drug or chemical exposures. To use the competitive ABPP approach effectively to understand potential adverse effects of chemicals of concern, a wide range of concentrations may be needed, particularly for chemicals that may lack toxicity data. In this work, we present an integral competitive ABPP method that enables target sensitivity differentiation across a wide range of concentrations for the model organophosphate (OP), paraoxon. Using previously developed OP-ABPs, we optimized conditions for tandem mass tag (TMT) multiplexing of ABPP samples and compared conventional competitive ABPP involving discrete samples at various paraoxon concentrations with pooling of samples across that same concentration range. The results show that small vs. large differences in integral intensities for the competitive sample can be used to distinguish low vs. high sensitivity proteins, respectively, without increasing the overall number of samples. We envision the integral ABPP method will provides a means to screen diverse chemicals more rapidly to identify both highly sensitive and less sensitive protein targets.
{"title":"An integral activity-based protein profiling (IABPP) method for higher throughput determination of protein target sensitivity to small molecules","authors":"Vivian S., Lin, Aaron T., Wright, Stephen J., Callister, Leo J., Gorham, Gerard X., Lomas, Agne, Sveistyte, John T., Melchior, Priscila M., Lalli, Chathuri J., Kombala, Tong, Zhang, Vanessa L., Paurus","doi":"10.26434/chemrxiv-2024-jg6bn","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-jg6bn","url":null,"abstract":"Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses chemical probes to label active enzymes selectively and covalently in complex proteomes. Competitive ABPP, which involves treatment of the active proteome with an analyte of interest, is especially powerful for profiling how small molecules impact specific protein activities. Advances in higher throughput workflows have made it possible to generate extensive competitive ABPP data across various biological systems and treatments, making this approach highly appealing for characterizing shared and unique proteins affected by perturbations such as drug or chemical exposures. To use the competitive ABPP approach effectively to understand potential adverse effects of chemicals of concern, a wide range of concentrations may be needed, particularly for chemicals that may lack toxicity data. In this work, we present an integral competitive ABPP method that enables target sensitivity differentiation across a wide range of concentrations for the model organophosphate (OP), paraoxon. Using previously developed OP-ABPs, we optimized conditions for tandem mass tag (TMT) multiplexing of ABPP samples and compared conventional competitive ABPP involving discrete samples at various paraoxon concentrations with pooling of samples across that same concentration range. The results show that small vs. large differences in integral intensities for the competitive sample can be used to distinguish low vs. high sensitivity proteins, respectively, without increasing the overall number of samples. We envision the integral ABPP method will provides a means to screen diverse chemicals more rapidly to identify both highly sensitive and less sensitive protein targets.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Most traditional optical biosensors operate through molecular recognition, where ligand binding causes conformational changes that lead to optical perturbations in the emitting motif. Optical sensors developed from single-strand DNA functionalized single-walled carbon nanotubes (ssDNA-SWCNT) have started to make useful contributions to biological research. However, the mechanisms underlying their function have remained poorly understood. In this study, we used a combination of experimental and computational approaches to show that ligand binding alone is not sufficient for optical modulation in this class of synthetic biosensors. Instead, the optical response that occurs after ligand binding is highly dependent on the chemical properties of the ligands, resembling mechanisms seen in activity-based biosensors. Specifically, we show that in ssDNA-SWCNT catecholamine sensors, the optical response correlates positively with electron density on the aryl motif, even when ligand binding affinities are similar. These findings could serve as a foundation for tuning the performance of existing sensors and guiding the development of new biosensors of this class.
大多数传统的光学生物传感器都是通过分子识别来工作的，配体结合会引起构象变化，从而导致发射图案的光学扰动。由单链 DNA 功能化单壁碳纳米管（ssDNA-SWCNT）开发的光学传感器已开始为生物研究做出有益的贡献。然而，人们对其功能的基本机制仍然知之甚少。在这项研究中，我们结合使用了实验和计算方法，结果表明在这类合成生物传感器中，仅靠配体结合不足以实现光学调制。相反，配体结合后产生的光学响应高度依赖于配体的化学特性，这与基于活性的生物传感器的机制相似。具体来说，我们发现在 ssDNA-SWCNT 儿茶酚胺传感器中，即使配体的结合亲和力相似，光学响应也与芳基基团上的电子密度呈正相关。这些发现可作为调整现有传感器性能的基础，并指导开发此类新型生物传感器。
{"title":"Molecular Determinants of Optical Modulation in ssDNA-Carbon Nanotube Biosensors: Insights from Experimental and Computational Approaches","authors":"Abraham, Beyene, Andrew, Krasley, Sayantani, Chakraborty, Lela, Vukovic","doi":"10.26434/chemrxiv-2024-8k2q2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-8k2q2","url":null,"abstract":"Most traditional optical biosensors operate through molecular recognition, where ligand binding causes conformational changes that lead to optical perturbations in the emitting motif. Optical sensors developed from single-strand DNA functionalized single-walled carbon nanotubes (ssDNA-SWCNT) have started to make useful contributions to biological research. However, the mechanisms underlying their function have remained poorly understood. In this study, we used a combination of experimental and computational approaches to show that ligand binding alone is not sufficient for optical modulation in this class of synthetic biosensors. Instead, the optical response that occurs after ligand binding is highly dependent on the chemical properties of the ligands, resembling mechanisms seen in activity-based biosensors. Specifically, we show that in ssDNA-SWCNT catecholamine sensors, the optical response correlates positively with electron density on the aryl motif, even when ligand binding affinities are similar. These findings could serve as a foundation for tuning the performance of existing sensors and guiding the development of new biosensors of this class.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several industrial processes are carried out on moving bed reactors (MBRs), and the development of mathematical models plays a fundamental role in designing, optimizing, and controlling these processes. Thus, this work initially develops a local solution for a linearized vertical MBR model to lumped parameters in the solid and fluid phases. Then, a semi-analytical solution (SAS) of the original nonlinear problem is obtained from the local solution. The SAS is easy to implement, stable, accurate, and performs fast, making it an efficient tool for MBR simulations. Excellent agreement was found comparing the SAS results with those of traditional numerical methods. SAS is capable of fast integration of model equations for systems with stiffness ratio SR=10^33. A numerical analysis was also carried out, indicating optimal refining parameters in relation to linearization error and machine error. The developments carried out can be easily extended to systems with multiple first-order reactions.
{"title":"Semi-Analytical Solution for a Lumped Model of a Co-Current Moving Bed Reactor","authors":"Natan, Padoin, Cíntia, Soares, Sávio , Bertoli, Jesús, Apolinar-Hernández, Carolina, Krebs de Souza, Marcel, Jeferson Gonçalves","doi":"10.26434/chemrxiv-2024-t30tv","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-t30tv","url":null,"abstract":"Several industrial processes are carried out on moving bed reactors (MBRs), and the development of mathematical models plays a fundamental role in designing, optimizing, and controlling these processes. Thus, this work initially develops a local solution for a linearized vertical MBR model to lumped parameters in the solid and fluid phases. Then, a semi-analytical solution (SAS) of the original nonlinear problem is obtained from the local solution. The SAS is easy to implement, stable, accurate, and performs fast, making it an efficient tool for MBR simulations. Excellent agreement was found comparing the SAS results with those of traditional numerical methods. SAS is capable of fast integration of model equations for systems with stiffness ratio SR=10^33. A numerical analysis was also carried out, indicating optimal refining parameters in relation to linearization error and machine error. The developments carried out can be easily extended to systems with multiple first-order reactions.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.26434/chemrxiv-2024-sfn8p
Mátyás, Pápai
The assessment of electronic structure descriptions utilized in the simulation of ultrafast excited-state dynamics of Fe(II) complexes is presented. Herein, we evaluate the performance of the RPBE, OPBE, BLYP, B3LYP, B3LYP*, CAM-B3LYP, and LC-BLYP (time-dependent) density functional theory (DFT/TD-DFT) methods in full-dimensional trajectory surface hopping (TSH) simulations carried out on linear vibronic coupling (LVC) potentials. We exploit the existence of time-resolved X-ray emission spectroscopy (XES) data for the [Fe(bmip)2]2+ and [Fe(terpy)2]2+ prototypes for dynamics between metal-to-ligand charge transfer (MLCT) and metal-centered (MC) states, which serve as a reference to benchmark the calculations (bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, terpy = 2,2’:6’,2''-terpyridine). The results show that the simulated ultrafast population dynamics between MLCT and MC states with various spin multiplicilities (singlet, triplet, quintet) highly depend on the utilized DFT/TD-DFT method with the percentage of exact (Hartree-Fock) exchange being the governing factor. Importantly, B3LYP* is the only DFT/TD-DFT method reproducing all important aspects of the experimentally resolved dynamics for both complexes, signalling an optimal balance in the description of MLCT-MC energetics. This work demonstrates the power of combining TSH/LVC dynamics simulations with time-resolved experimental reference data to benchmark full-dimensional potential energy surfaces.
{"title":"Simulation of Ultrafast Excited-State Dynamics in Fe(II) Complexes: Assessment of Electronic Structure Descriptions","authors":"Mátyás, Pápai","doi":"10.26434/chemrxiv-2024-sfn8p","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-sfn8p","url":null,"abstract":"The assessment of electronic structure descriptions utilized in the simulation of ultrafast excited-state dynamics of Fe(II) complexes is presented. Herein, we evaluate the performance of the RPBE, OPBE, BLYP, B3LYP, B3LYP*, CAM-B3LYP, and LC-BLYP (time-dependent) density functional theory (DFT/TD-DFT) methods in full-dimensional trajectory surface hopping (TSH) simulations carried out on linear vibronic coupling (LVC) potentials. We exploit the existence of time-resolved X-ray emission spectroscopy (XES) data for the [Fe(bmip)2]2+ and [Fe(terpy)2]2+ prototypes for dynamics between metal-to-ligand charge transfer (MLCT) and metal-centered (MC) states, which serve as a reference to benchmark the calculations (bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, terpy = 2,2’:6’,2''-terpyridine). The results show that the simulated ultrafast population dynamics between MLCT and MC states with various spin multiplicilities (singlet, triplet, quintet) highly depend on the utilized DFT/TD-DFT method with the percentage of exact (Hartree-Fock) exchange being the governing factor. Importantly, B3LYP* is the only DFT/TD-DFT method reproducing all important aspects of the experimentally resolved dynamics for both complexes, signalling an optimal balance in the description of MLCT-MC energetics. This work demonstrates the power of combining TSH/LVC dynamics simulations with time-resolved experimental reference data to benchmark full-dimensional potential energy surfaces.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.26434/chemrxiv-2024-ng3ws
Pavlo O., Dral, Yuxinxin, Chen
Machine learning (ML) potentials typically target a single quantum chemical (QC) level while the ML models developed for multi-fidelity learning have not been shown to provide scalable solutions for foundational models. Here we introduce the all-in-one (AIO) ANI model architecture based on multimodal learning which can learn an arbitrary number of QC levels. Our all-in-one learning approach offers a more general and easier-to-use alternative to transfer learning. We use it to train the AIO-ANI-UIP foundational model with the generalization capability comparable to semi-empirical GFN2-xTB and DFT with a double-zeta basis set for organic molecules. We show that the AIO-ANI model can learn across different QC levels ranging from semi-empirical to density functional theory to coupled cluster. We also use AIO models to design the foundational model Δ-AIO-ANI based on Δ-learning with increased accuracy and robustness compared to AIO-ANI-UIP. The code and the foundational models are available at https://github.com/dralgroup/aio-ani; they will be integrated into the universal and updatable AI-enhanced QM (UAIQM) library and made available in the MLatom package so that they can be used online at the XACS cloud computing platform (see https://github.com/dralgroup/mlatom for updates).
{"title":"All-in-one foundational models learning across quantum chemical levels","authors":"Pavlo O., Dral, Yuxinxin, Chen","doi":"10.26434/chemrxiv-2024-ng3ws","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-ng3ws","url":null,"abstract":"Machine learning (ML) potentials typically target a single quantum chemical (QC) level while the ML models developed for multi-fidelity learning have not been shown to provide scalable solutions for foundational models. Here we introduce the all-in-one (AIO) ANI model architecture based on multimodal learning which can learn an arbitrary number of QC levels. Our all-in-one learning approach offers a more general and easier-to-use alternative to transfer learning. We use it to train the AIO-ANI-UIP foundational model with the generalization capability comparable to semi-empirical GFN2-xTB and DFT with a double-zeta basis set for organic molecules. We show that the AIO-ANI model can learn across different QC levels ranging from semi-empirical to density functional theory to coupled cluster. We also use AIO models to design the foundational model Δ-AIO-ANI based on Δ-learning with increased accuracy and robustness compared to AIO-ANI-UIP. The code and the foundational models are available at https://github.com/dralgroup/aio-ani; they will be integrated into the universal and updatable AI-enhanced QM (UAIQM) library and made available in the MLatom package so that they can be used online at the XACS cloud computing platform (see https://github.com/dralgroup/mlatom for updates).","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polyolefins are ubiquitous in consumer products but are notoriously difficult to recycle due to the inherent incompatibility of their common varieties. Existing approaches to addressing this challenge either require complex syntheses or compromise the properties of the parent materials. Here, a new method to compatibilize mixed polyolefins is developed. With a single-step photocatalysis, acid or base functionality can be readily installed onto polyolefins. The combination of acid- and base-modified polyolefins functions as compatibilizers. Incorporating them into polyolefin blends results in excellent mechanical strength, with up to an 82-fold increase in ductility. Importantly, compatibilization can be readily achieved on post-consumer polyolefin mixtures. Furthermore, direct functionalization and compatibilization of polyolefin blends is achieved. This strategy promises to transform polyolefin recycling and will likely find broad applications.
{"title":"Compatibilization of polyolefin blends through acid–base interactions","authors":"Yucheng, Yuan, Jiawei, He, Jiangwei, Liu, Ming-Chi, Wang, Tuhin, Ganguly, John, Santoro, Junpeng, Wang, Jeffery, Byers, Jia, Niu, Mingjiang, Zhong, Dunwei, Wang","doi":"10.26434/chemrxiv-2024-qhsj9","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-qhsj9","url":null,"abstract":"Polyolefins are ubiquitous in consumer products but are notoriously difficult to recycle due to the inherent incompatibility of their common varieties. Existing approaches to addressing this challenge either require complex syntheses or compromise the properties of the parent materials. Here, a new method to compatibilize mixed polyolefins is developed. With a single-step photocatalysis, acid or base functionality can be readily installed onto polyolefins. The combination of acid- and base-modified polyolefins functions as compatibilizers. Incorporating them into polyolefin blends results in excellent mechanical strength, with up to an 82-fold increase in ductility. Importantly, compatibilization can be readily achieved on post-consumer polyolefin mixtures. Furthermore, direct functionalization and compatibilization of polyolefin blends is achieved. This strategy promises to transform polyolefin recycling and will likely find broad applications.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.26434/chemrxiv-2024-vxdq4
Yatong, Wang, Geert, Brocks, Ceren, Tayran, Süleyman, Er
Two-dimensional (2D) Janus materials gain increasing attention as water splitting photocatalysts for hydrogen production. We use first-principles calculations to predict a stable 2D Janus $T$-TiNBr structure, with strong near-ultraviolet sunlight absorption and band edges that align favorably with the water redox potentials for oxygen and hydrogen evolution. We show that the optical and electronic properties of $T$-TiNBr can be modulated to a certain extend by applying external uniaxial strain. Explicit calculations of the redox reactions reveal that solar-driven water splitting is viable at the N-side of $T$-TiNBr, while the Br-side requires modifications such as vacancy creation, the application of an external potential, or adjustment of the pH conditions.
{"title":"2D TiNBr as photocatalyst for overall water splitting","authors":"Yatong, Wang, Geert, Brocks, Ceren, Tayran, Süleyman, Er","doi":"10.26434/chemrxiv-2024-vxdq4","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-vxdq4","url":null,"abstract":"Two-dimensional (2D) Janus materials gain increasing attention as water splitting photocatalysts for hydrogen production. We use first-principles calculations to predict a stable 2D Janus $T$-TiNBr structure, with strong near-ultraviolet sunlight absorption and band edges that align favorably with the water redox potentials for oxygen and hydrogen evolution. We show that the optical and electronic properties of $T$-TiNBr can be modulated to a certain extend by applying external uniaxial strain. Explicit calculations of the redox reactions reveal that solar-driven water splitting is viable at the N-side of $T$-TiNBr, while the Br-side requires modifications such as vacancy creation, the application of an external potential, or adjustment of the pH conditions.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.26434/chemrxiv-2024-mfpcn
Dhiman, Ray, Valerio, Rizzi
We introduce an enhanced sampling algorithm to obtain converged free energy landscapes of molecular rare events, even when the collective variable (CV) used for biasing is not optimal. Our approach is a combination of the On-the-fly probability enhanced sampling (OPES) and its exploratory variant, OPES Explore (OPESe). We demonstrate the successful application of this combined algorithm on the two-dimensional Wolfe-Quapp potential, ligand-receptor binding in trypsin-benzamidine complex, and folding-unfolding of chignolin. Apart from computing accurate free energy profiles, we can discover additional metastable configurations not distinguished by the sub-optimal CV space. Moreover, we can control the trade-off between accuracy and convergence speed by varying the ratio of the barrier parameters in OPES and OPESe components. The improved efficiency and accuracy of free energy calculation, and the possibility of using generic and intuitive collective variables, make our proposed algorithm particularly promising for the simulation of complex molecular systems.
我们介绍了一种增强采样算法，即使用于偏置的集体变量（CV）不是最佳的，也能获得收敛的分子稀有事件自由能景观。我们的方法是即时概率增强采样（OPES）及其探索变体 OPES Explore（OPESe）的结合。我们展示了这一组合算法在二维 Wolfe-Quapp 势、胰蛋白酶-苯甲脒复合物中配体-受体结合以及木犀草素的折叠-解折上的成功应用。除了计算精确的自由能曲线外，我们还能发现次优 CV 空间无法区分的其他可转移构型。此外，我们还可以通过改变 OPES 和 OPESe 组件中势垒参数的比例来控制精度和收敛速度之间的权衡。自由能计算效率和精度的提高，以及使用通用直观集合变量的可能性，使我们提出的算法在复杂分子系统的模拟中大有可为。
{"title":"Enhanced Sampling with Sub-optimal Collective Variables: Reconciling Accuracy and Convergence Speed","authors":"Dhiman, Ray, Valerio, Rizzi","doi":"10.26434/chemrxiv-2024-mfpcn","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-mfpcn","url":null,"abstract":"We introduce an enhanced sampling algorithm to obtain converged free energy landscapes of molecular rare events, even when the collective variable (CV) used for biasing is not optimal. Our approach is a combination of the On-the-fly probability enhanced sampling (OPES) and its exploratory variant, OPES Explore (OPESe). We demonstrate the successful application of this combined algorithm on the two-dimensional Wolfe-Quapp potential, ligand-receptor binding in trypsin-benzamidine complex, and folding-unfolding of chignolin. Apart from computing accurate free energy profiles, we can discover additional metastable configurations not distinguished by the sub-optimal CV space. Moreover, we can control the trade-off between accuracy and convergence speed by varying the ratio of the barrier parameters in OPES and OPESe components. The improved efficiency and accuracy of free energy calculation, and the possibility of using generic and intuitive collective variables, make our proposed algorithm particularly promising for the simulation of complex molecular systems.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We have evaluated the antibacterial activity of the essential oil of the leaves of Coreopsis lanceolata (CL-EO) collected in southeastern Brazil. against a representative panel of cariogenic bacteria. The activity was evaluated in terms of its Minimum Inhibitory Concentration (MIC) values. CL-EO displays moderate activity against Streptococcus mutans, S. sanguinis, S. salivarus, S. sobrinus, Lactobacillus paracasei, and Enterococcus faecalis (MIC = 1000 µg/mL) and strong activity against S. mitis (MIC = 500 µg/mL). We have identified 1,11-tridecadiene-3,5,7,9-tetrayne (48.9%), β-bisabolene (22.8%), germacrene D (9.2%), and globulol (4.6%) as the major compounds in CL-EO. This is the first report on the chemical composition of the essential oil obtained from C. lanceolata leaves.
{"title":"Chemical composition and antibacterial activity of the essential oil of Coreopsis lanceolata leaves","authors":"Antônio, Crotti, Richard, Lima, Ana Carla, Colli, Sara, Souza, Milton, Groppo, Carlos, Martins","doi":"10.26434/chemrxiv-2024-dk7v6","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-dk7v6","url":null,"abstract":"We have evaluated the antibacterial activity of the essential oil of the leaves of Coreopsis lanceolata (CL-EO) collected in southeastern Brazil. against a representative panel of cariogenic bacteria. The activity was evaluated in terms of its Minimum Inhibitory Concentration (MIC) values. CL-EO displays moderate activity against Streptococcus mutans, S. sanguinis, S. salivarus, S. sobrinus, Lactobacillus paracasei, and Enterococcus faecalis (MIC = 1000 µg/mL) and strong activity against S. mitis (MIC = 500 µg/mL). We have identified 1,11-tridecadiene-3,5,7,9-tetrayne (48.9%), β-bisabolene (22.8%), germacrene D (9.2%), and globulol (4.6%) as the major compounds in CL-EO. This is the first report on the chemical composition of the essential oil obtained from C. lanceolata leaves.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of chemoselective defluorination reactions is highly desirable due to the exceptional stability of the C–F bond compared to other functional groups. Recent advances in photocatalysis have enabled cataytic single-electron transfer (SET) processes, offering an alternative to stoichiometric methods that rely on strong reducing agents. However, these strategies have primarily focused on trifluoromethyl substrates, with limited success for compounds containing fewer fluorine atoms, which are inherently more resistant to SET. Herein, we report a novel defluorination strategy for α-fluorocarbonyl compounds, employing zirconocene and photoredox catalysis. Our method leverages the strong fluorine affinity of zirconocene and bypassed reliance on reduction potential, focusing instead on the bond dissociation energy of the fluorinated molecules. This methodology offers a complementary ap-proach for catalytic C–F bond cleavage under visible-light conditions.
与其他官能团相比，C-F 键具有极高的稳定性，因此开发化学选择性脱氟反应非常有必要。光催化技术的最新进展实现了催化单电子转移（SET）过程，为依赖强还原剂的化学计量法提供了替代方案。然而，这些策略主要集中在三氟甲基底物上，而对于含氟原子较少的化合物则成效有限，因为这些化合物对 SET 本身具有更强的抵抗力。在此，我们报告了一种新型的α-氟羰基化合物脱氟方法，该方法采用锆烯和光氧化催化。我们的方法利用了二茂锆的强氟亲和力，绕过了对还原电位的依赖，转而关注氟化分子的键解离能。这种方法为在可见光条件下催化 C-F 键裂解提供了一种补充方法。
{"title":"Reversing the Chemoselectivity in Photocatalytic C–F Bond Cleavage Enabled by Zirconocene and Photoredox Catalysis","authors":"Junichiro, Yamaguchi, Haruki, Takimoto, Kazuhiro, Aida, Yoshio, Nishimoto, Daisuke, Yokogawa, Eisuke, Ota","doi":"10.26434/chemrxiv-2024-ssj00","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-ssj00","url":null,"abstract":"The development of chemoselective defluorination reactions is highly desirable due to the exceptional stability of the C–F bond compared to other functional groups. Recent advances in photocatalysis have enabled cataytic single-electron transfer (SET) processes, offering an alternative to stoichiometric methods that rely on strong reducing agents. However, these strategies have primarily focused on trifluoromethyl substrates, with limited success for compounds containing fewer fluorine atoms, which are inherently more resistant to SET. Herein, we report a novel defluorination strategy for α-fluorocarbonyl compounds, employing zirconocene and photoredox catalysis. Our method leverages the strong fluorine affinity of zirconocene and bypassed reliance on reduction potential, focusing instead on the bond dissociation energy of the fluorinated molecules. This methodology offers a complementary ap-proach for catalytic C–F bond cleavage under visible-light conditions.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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