ACS Publications最新文献_第7页

Formation of β-U₃O₈ from UCl₃ Salt Compositions under Oxygen Exposure. UCl3 盐成分在氧气暴露下形成 β-U3O8

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-11-14 Epub Date: 2024-11-05 DOI: 10.1021/acs.jpcb.4c02776

Benjamin W Tuffy, Nancy R Birkner, Juliano Schorne-Pinto, Ryan C Davis, Amir M Mofrad, Clara M Dixon, Mina Aziziha, Matthew S Christian, Timothy J Lynch, Maxwell T Bartlett, Theodore M Besmann, Kyle S Brinkman, Wilson K S Chiu

{"title":"Formation of β-U3O8 from UCl3 Salt Compositions under Oxygen Exposure.","authors":"Benjamin W Tuffy, Nancy R Birkner, Juliano Schorne-Pinto, Ryan C Davis, Amir M Mofrad, Clara M Dixon, Mina Aziziha, Matthew S Christian, Timothy J Lynch, Maxwell T Bartlett, Theodore M Besmann, Kyle S Brinkman, Wilson K S Chiu","doi":"10.1021/acs.jpcb.4c02776","DOIUrl":"10.1021/acs.jpcb.4c02776","url":null,"abstract":"Complementary X-ray absorption fine structure (XAFS) and Raman spectroscopy studies were conducted on various UCl3 concentrations in alkali chloride salt compositions. The samples were 5 mol % UCl3 in LiCl (S1), 5 mol % UCl3 in KCl (S2), 5 mol % UCl3 in LiCl-KCl eutectic (S4), 50 mol % UCl3 in KCl (S5), and 20 mol % UCl3 in KCl (S6) molar concentrations. Samples were heated to 800 °C and allowed to cool to room temperature with measurements performed at selected temperatures; the highest temperatures showed the most stability and will be primarily referenced for conclusions. The processing and interpretation of the Raman and extended X-ray absorption fine structure (EXAFS) peaks revealed several uranium-oxygen bond lengths and symmetries in the samples before, during, and after heating. Based on published thermodynamic data of similar systems, X-ray absorption fine structure spectroscopy, and identification of Raman peaks, a β variation of α-U3O8, typical at room temperature, is the suspected dominant phase of all samples at high temperatures (800 °C). In the existing literature, this β structure of U3O8 was synthesized by slow cooling of uranium oxides from 1350 °C. This paper suggests the rapid formation of the compound due to the decomposition of the uranium chlorides or oxychlorides at increasing temperatures and O2 reaction kinetics.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Explicit Configurational Entropy of Mixing in Molecular Dynamics Simulations. 分子动力学模拟中混合的显式构型熵。

IF 4.8 2区化学

The Journal of Physical Chemistry Letters Pub Date : 2024-11-14 Epub Date: 2024-11-05 DOI: 10.1021/acs.jpclett.4c02819

T Hanke, A L Upterworth, D Sebastiani

引用次数: 0

Luminescence and Transport Behavior in Incommensurately Modulated CaGd₂(MoO₄)₄:Yb/Er. 不可比调制 CaGd2(MoO4)4:Yb/Er.中的发光和传输行为

IF 4.8 2区化学

The Journal of Physical Chemistry Letters Pub Date : 2024-11-14 Epub Date: 2024-11-06 DOI: 10.1021/acs.jpclett.4c02554

Yinghan Wang, Zeyue Zhang, Guohong Cai, Jingxie Xiong, Zhengren Tao, Chunhai Wang, Junliang Sun, Shi Ye

{"title":"Luminescence and Transport Behavior in Incommensurately Modulated CaGd2(MoO4)4:Yb/Er.","authors":"Yinghan Wang, Zeyue Zhang, Guohong Cai, Jingxie Xiong, Zhengren Tao, Chunhai Wang, Junliang Sun, Shi Ye","doi":"10.1021/acs.jpclett.4c02554","DOIUrl":"10.1021/acs.jpclett.4c02554","url":null,"abstract":"The phenomenon of thermal quenching of luminescence can significantly compromise the efficiency of luminescent materials, a process accompanied by the generation of substantial phonon populations. While plenty of models for elucidating this behavior have been proposed, the crucial role of phonon transport has largely been neglected, particularly in the enigmatic incommensurate scheelite structure with good luminescence performance. In this study, we delve into the thermal quenching dynamics of the near-infrared emission in the incommensurately modulated CaGd2(MoO4)4:Yb/Er system. Our comprehensive investigation reveals distinct evolutionary patterns in electrical conductivity, luminescence intensity, thermal conductivity, and Raman scattering at varying temperature regimes. Notably, we have determined that thermally induced ion migration, occurring above ∼300 °C, serves as a pivotal trigger for the activation of all phonons and the enhancement of phonon-defect scattering within this incommensurate framework. This phenomenon not only diminishes the thermal conductivity but also accelerates the multiphonon relaxation of the Er3+ emission levels, culminating in a marked thermal quenching of luminescence. This work illuminates the thermal quenching mechanism of luminescence by focusing on phonon scattering dynamics, providing critical insights for the design of thermally robust near-infrared luminescent materials, which are essential for the advancement of optical amplification systems.","PeriodicalId":62,"journal":{"name":"The Journal of Physical Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of BAY 2413555, First Selective Positive Allosteric Modulator of the M2 Receptor to Restore Cardiac Autonomic Balance. 发现 BAY 2413555--首个恢复心脏自主神经平衡的 M2 受体选择性正性异构调节剂。

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-11-14 Epub Date: 2024-10-28 DOI: 10.1021/acs.jmedchem.4c01590

Alexandros Vakalopoulos, Daniel Basting, Markus Brechmann, Henrik Teller, Melissa Boultadakis Arapinis, Alexander Straub, Joachim Mittendorf, Mark Meininghaus, Thomas Müller, Katrin Nowak-Reppel, Martina Schäfer, Matthias Wittwer, Maximilian Kullmann, Carsten Terjung, Dieter Lang, Thorsten Poethko, Tobias Marquardt, Till Freudenberger, Thomas Mondritzki, Jörg Hüser, Michael Heckmann, Hanna Tinel

{"title":"Discovery of BAY 2413555, First Selective Positive Allosteric Modulator of the M2 Receptor to Restore Cardiac Autonomic Balance.","authors":"Alexandros Vakalopoulos, Daniel Basting, Markus Brechmann, Henrik Teller, Melissa Boultadakis Arapinis, Alexander Straub, Joachim Mittendorf, Mark Meininghaus, Thomas Müller, Katrin Nowak-Reppel, Martina Schäfer, Matthias Wittwer, Maximilian Kullmann, Carsten Terjung, Dieter Lang, Thorsten Poethko, Tobias Marquardt, Till Freudenberger, Thomas Mondritzki, Jörg Hüser, Michael Heckmann, Hanna Tinel","doi":"10.1021/acs.jmedchem.4c01590","DOIUrl":"10.1021/acs.jmedchem.4c01590","url":null,"abstract":"Autonomic disbalance, i.e., sympathetic overactivation and parasympathetic withdrawal, is a causal driver of disease progression in heart failure. While sympatholytic drugs are established treatments, no drug therapy restoring vagal control of cardiac function is available. We report here the HTS-based discovery of a novel class of 1,8-naphthyridin-4(1H)-one carboxamides acting as positive allosteric modulators (PAMs) of the M2 muscarinic acetylcholine receptor (M2R). M2R is the main postsynaptic myocyte receptor regulating heart rate, electrical conduction, and contractile strength. Extensive optimization of the screening hit in terms of potency, permeation, metabolic stability, and solubility ultimately resulted in the discovery of the first-in-class clinical candidate BAY 2413555 (27). With an overall technical profile compatible with once-daily oral administration in a phase 1 study, no apparent effects on blood pressure, and a mechanism that largely preserves autonomic regulatory capacity, BAY 2413555 could be the tool to finally study the restoration of autonomic balance.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perspective for Drug Discovery Targeting SARS Coronavirus Methyltransferases: Function, Structure and Inhibition. 针对 SARS 冠状病毒甲基转移酶的药物研发展望：功能、结构和抑制。

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-11-14 Epub Date: 2024-10-31 DOI: 10.1021/acs.jmedchem.4c01749

Xin Li, Yongcheng Song

引用次数: 0

A Prostate-Specific Membrane Antigen-Targeting Small Molecule-Drug Conjugate Strategy to Overcome the Hematological Toxicity of Olaparib. 克服奥拉帕利血液学毒性的前列腺特异性膜抗原靶向小分子药物共轭物策略

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-11-14 Epub Date: 2024-10-31 DOI: 10.1021/acs.jmedchem.4c01910

Qi Chen, Zhenying Wu, Haiying Zhu, Xi Zhang, Yongping Yu, Wenteng Chen

{"title":"A Prostate-Specific Membrane Antigen-Targeting Small Molecule-Drug Conjugate Strategy to Overcome the Hematological Toxicity of Olaparib.","authors":"Qi Chen, Zhenying Wu, Haiying Zhu, Xi Zhang, Yongping Yu, Wenteng Chen","doi":"10.1021/acs.jmedchem.4c01910","DOIUrl":"10.1021/acs.jmedchem.4c01910","url":null,"abstract":"PARP inhibitors have gained attention in the treatment of metastatic castration-resistant prostate cancer, but approximately half of patients have to abort treatment due to severe hematological toxicity. Herein, we proposed a prostate-specific membrane antigen (PSMA)-targeting small molecule-drug conjugate (SMDC) strategy to address this issue. This led to CQ-16, which achieved its targeting to prostate tumor cells through binding to PSMA. Also, CQ-16 retained the PARP inhibitory activity and exhibited highly selective antiproliferative activities between PSMA-positive and PSMA-negative prostate cells. Moreover, the hematological toxicity observed in Olaparib was not showing in the group of CQ-16 even at a high dose of 390 mg/kg. Moreover, oral administration of CQ-16 exerted significant tumor growth inhibition in the 22Rv1 xenograft mouse model. These above findings not only highlight the potential of CQ-16 to overcome the hematological toxicity associated with PARP inhibitors but also provide a strategy to develop an SMDC with enhanced safety profiles.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Palladium-Mediated Bioorthogonal System for Prodrug Activation of N-Benzylbenzamide-Containing Tubulin Polymerization Inhibitors for the Treatment of Solid Tumors. 钯介导的生物正交系统，用于原药激活含 N-苄基苯甲酰胺的管蛋白聚合抑制剂以治疗实体瘤。

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-11-14 Epub Date: 2024-11-01 DOI: 10.1021/acs.jmedchem.4c02419

Jinlong Li, Tong Zhang, Di Wu, Chen He, Haoxiang Weng, Tiandong Zheng, Jie Liu, Hong Yao, Jichao Chen, Yansong Ren, Zheying Zhu, Jinyi Xu, Shengtao Xu

{"title":"Palladium-Mediated Bioorthogonal System for Prodrug Activation of N-Benzylbenzamide-Containing Tubulin Polymerization Inhibitors for the Treatment of Solid Tumors.","authors":"Jinlong Li, Tong Zhang, Di Wu, Chen He, Haoxiang Weng, Tiandong Zheng, Jie Liu, Hong Yao, Jichao Chen, Yansong Ren, Zheying Zhu, Jinyi Xu, Shengtao Xu","doi":"10.1021/acs.jmedchem.4c02419","DOIUrl":"10.1021/acs.jmedchem.4c02419","url":null,"abstract":"Bioorthogonal cleavage reactions have been developed as an intriguing strategy to enhance the safety of chemotherapeutics. Aiming to reduce the toxicity and improve the targeted release properties of the colchicine binding site inhibitors (CBSIs) based on previous work, a series of biologically inert prodrugs were further designed and synthesized through a bioorthogonal prodrug strategy. The therapeutic effects of prodrugs could be \"turned-on\" once combined with palladium resins. Particularly, prodrug 2b was 68.3-fold less cytotoxic compared to the parent compound, while its cytotoxicity was recovered in situ in the presence of palladium resins. Mechanism studies confirmed that 2b inhibited cell growth in the same manner as CBSIs. More importantly, in vivo efficacy studies demonstrated the efficient activation of 2b by palladium resins, resulting in significant inhibition of tumor growth (63.2%). These results suggest that prodrug 2b with improved safety and targeted release property catalyzed by a Pd-mediated bioorthogonal cleavage reaction deserves further investigation.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

G-Quadruplex Recognition by Tetraalkylammonium Ions: A New Paradigm for Discrimination between Parallel and Antiparallel G-Quadruplexes. 四烷基铵离子识别 G-四重链：区分平行和反平行 G-四重链的新范例。

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-11-14 Epub Date: 2024-10-31 DOI: 10.1021/acs.jpcb.4c06355

Xuan Li, David N Dubins, Jens Völker, Tigran V Chalikian

{"title":"G-Quadruplex Recognition by Tetraalkylammonium Ions: A New Paradigm for Discrimination between Parallel and Antiparallel G-Quadruplexes.","authors":"Xuan Li, David N Dubins, Jens Völker, Tigran V Chalikian","doi":"10.1021/acs.jpcb.4c06355","DOIUrl":"10.1021/acs.jpcb.4c06355","url":null,"abstract":"G-quadruplexes are an important class of noncanonical secondary structures of DNA that exist in the cell and are involved in the regulation of principal genomic events. Any regulatory role of a G-quadruplex in the genome is coupled with the attendant interconversions between the G-quadruplex and duplex states. Much effort has been invested in the quest for agents that can recognize individual G-quadruplexes and shift the associated duplex-G-quadruplex equilibria toward the G-quadruplex state. In this communication, we demonstrate that, notwithstanding their simplicity, tetraalkylammonium ions, [H(CH2)n]4N+, recognize and strongly stabilize the parallel c-MYC G-quadruplex, while not binding to the antiparallel human telomeric G-quadruplex or duplex DNA. The affinity of TAA+ ions for the c-MYC G-quadruplex correlates with the length of the aliphatic side chains. Our CD spectral data suggest that the binding of tetraalkylammonium ions is external, not resulting in structural changes in the host G-quadruplex. The observed discriminatory power identifies tetraalkylammonium salts as a starting point for developing topology-selective G-quadruplex-binding agents.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atmospheric Degradation of CH₂═C(CH₃)C(O)O[CH₂]₄CH₃ by ^•OH Radicals: Reactivity, POCP, and Carbonyl Formation. 大气中 -OH 自由基对 CH2═C(CH3)C(O)O[CH2]4CH3 的降解作用：反应性、POCP 和羰基形成。

IF 2.7 2区化学

The Journal of Physical Chemistry A Pub Date : 2024-11-14 Epub Date: 2024-11-01 DOI: 10.1021/acs.jpca.4c04393

Vianni Giovanna Straccia Cepeda, María B Blanco, Mariano Teruel

{"title":"Atmospheric Degradation of CH2═C(CH3)C(O)O[CH2]4CH3 by •OH Radicals: Reactivity, POCP, and Carbonyl Formation.","authors":"Vianni Giovanna Straccia Cepeda, María B Blanco, Mariano Teruel","doi":"10.1021/acs.jpca.4c04393","DOIUrl":"10.1021/acs.jpca.4c04393","url":null,"abstract":"Relative rate studies of the gas-phase reaction of amyl methacrylate, CH2═C(CH3)C(O)O[CH2]4CH3, with •OH radicals were performed at (298 ± 2) K and 1000 mbar. The experiments were conducted in an atmospheric Pyrex chamber coupled to in situ Fourier transform infrared spectroscopy (FTIR). The rate coefficient obtained from the average of several experiments was kAMMA+•OH = (8.10 ± 1.98) × 10-11 cm3 molecule-1 s-1. Additionally, product studies were conducted under conditions similar to those of the kinetic experiments by using in situ FTIR spectroscopy. Pentanal, butanal, and hydroxyacetone were identified as the main reaction products. The initial pathway for the degradation of amyl methacrylate with •OH radicals occurs via addition of •OH to the >C═C< bond or hydrogen abstraction from the alkyl chain of the ester. The likelihood of hydrogen atom abstraction is 25%, while the addition of hydroxyl radicals to the double bond occurs with a probability of 75%. Based on these outcomes, a degradation mechanism is postulated. Furthermore, the atmospheric implications of the studied reaction were evaluated by estimating the tropospheric lifetime of amyl methacrylate toward •OH radicals as τOH = 3.43 h. Additionally, the Photochemical Ozone Creation Potential (POCP) of 84 was calculated for the reaction studied. Carbonyl compounds found as reaction products can exert a substantial influence on both air quality and public health.","PeriodicalId":59,"journal":{"name":"The Journal of Physical Chemistry A","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Oral Bioavailable Coumarin Derivatives as Potential AR Antagonists Targeting Prostate Cancer. 鉴定可口服生物利用的香豆素衍生物作为针对前列腺癌的潜在 AR 拮抗剂。

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-11-14 Epub Date: 2024-11-04 DOI: 10.1021/acs.jmedchem.4c01752

Jinbiao Liao, Jianing Liao, Minkui Zhang, Yanzhen Yu, Lvtao Cai, Kaixin Le, Weitao Fu, Yiyang Qin, Tingjun Hou, Dan Li, Rong Sheng

{"title":"Identification of Oral Bioavailable Coumarin Derivatives as Potential AR Antagonists Targeting Prostate Cancer.","authors":"Jinbiao Liao, Jianing Liao, Minkui Zhang, Yanzhen Yu, Lvtao Cai, Kaixin Le, Weitao Fu, Yiyang Qin, Tingjun Hou, Dan Li, Rong Sheng","doi":"10.1021/acs.jmedchem.4c01752","DOIUrl":"10.1021/acs.jmedchem.4c01752","url":null,"abstract":"Androgen receptor (AR) is a crucial driver of prostate cancer (PCa), but acquired resistance to AR antagonists significantly undermines their clinical efficacy. We previously discovered coumarin derivative 1, which is capable of disrupting AR ligand-binding domain dimers, offering the potential for overcoming resistance. However, its poor oral bioavailability limited further development. In this study, comprehensive structure optimizations led to compound 4a (IC50 = 0.051 μM), which exhibited comparable AR antagonistic activity to enzalutamide (IC50 = 0.060 μM) and demonstrated excellent selectivity over other nuclear receptors in vitro. Especially, 4a showed superior efficacy against ARF876L/T877A and ARW741C mutants compared to darolutamide and enzalutamide. Moreover, 4a exhibited favorable pharmacokinetic profiles (F = 66.24%) in vivo and significant tumor growth inhibition in an LNCaP xenograft mouse model upon oral administration. These results highlight the potential of 4a as a promising oral AR antagonist for overcoming drug resistance in PCa.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0