Pub Date : 2024-07-05DOI: 10.1021/acs.orglett.4c02030
Nuermaimaiti Yisimayili, Zheng-Fei Li, Tao Liu, Chong-Dao Lu
Current methods for the asymmetric α-sulfenylation of carbonyls cannot be applied to acyclic carbonyls that have two similar substituents at the α-position. This research demonstrated that the electrophilic sulfenylation of geometry-defined acyclic β,β-disubstituted enesulfinamides using S-aryl or S-alkyl benzenethiosulfonates can be highly stereoselective. This process results in enantioenriched α,α-disubstituted α-sulfenylated ketone surrogates with sulfur-containing acyclic tetrasubstituted carbon stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl). Furthermore, by employing the corresponding stereoisomers of enensulfinamides, any of the four stereoisomers of α-sulfenylated ketimines can be selectively accessed.
{"title":"Stereoselective Electrophilic Sulfenylation of β,β-Disubstituted Enesulfinamides: Asymmetric Construction of Less Accessible Acyclic α,α-Disubstituted α-Sulfenylated Ketimines.","authors":"Nuermaimaiti Yisimayili, Zheng-Fei Li, Tao Liu, Chong-Dao Lu","doi":"10.1021/acs.orglett.4c02030","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c02030","url":null,"abstract":"<p><p>Current methods for the asymmetric α-sulfenylation of carbonyls cannot be applied to acyclic carbonyls that have two similar substituents at the α-position. This research demonstrated that the electrophilic sulfenylation of geometry-defined acyclic β,β-disubstituted enesulfinamides using <i>S</i>-aryl or <i>S</i>-alkyl benzenethiosulfonates can be highly stereoselective. This process results in enantioenriched α,α-disubstituted α-sulfenylated ketone surrogates with sulfur-containing acyclic tetrasubstituted carbon stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl). Furthermore, by employing the corresponding stereoisomers of enensulfinamides, any of the four stereoisomers of α-sulfenylated ketimines can be selectively accessed.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1021/acs.langmuir.4c00753
Pu Feng, Jun Liu, Lian-Jun Bao, Eddy Y Zeng, Chunfeng Ma, Lingling Wang, Guangzhao Zhang, Xiangjun Gong
Marine antibiofouling using low-amplitude electric pulses (EP) is an energy-efficient and eco-friendly approach, but potential mechanisms for preventing biofouling remain unclear. In the present study, the 3D adhesion dynamics of a model microorganism─Pseudomonas aeruginosa (PAO1)─under low-amplitude cathodic EP were examined as a function of applying voltage and its duration (td). The results demonstrated that adhered bacteria escaped from the electrode surface even when EP was removed. The escaped bacteria ratio, induction period of escape, and duration of the detachment were influenced profoundly by EP amplitude but slightly by td when td ≥ 5 min. The acceleration of escaped PAO1 from the surface indicated that their flagellar motor was powered by EP. Particularly, EP enabled swimming bacteria to have adaptive motions that were sustainable and regulated by the gene rsmA. As a result, they had less accumulation near the surface. The propulsion of adhered bacteria and adaptive escape of swimming bacteria were enhanced in response to low-amplitude EP. Hence, low-amplitude and short-duration EP is promising for sustainable antibiofouling applications.
利用低振幅电脉冲(EP)进行海洋生物防污是一种节能环保的方法,但防止生物污染的潜在机制仍不清楚。在本研究中,研究人员考察了模型微生物--铜绿假单胞菌(PAO1)--在低幅阴极电脉冲下的三维粘附动态,并将其作为施加电压及其持续时间(td)的函数。结果表明,即使去除极压,附着的细菌也会从电极表面逃逸。逸出细菌比率、逸出诱导期和脱离持续时间受 EP 振幅的影响很大,但在 td ≥ 5 分钟时受 td 的影响较小。从表面逃逸的 PAO1 的加速度表明,它们的鞭毛运动是由 EP 驱动的。特别是,EP 使游动的细菌能够在 rsmA 基因的调控下进行可持续的适应性运动。因此,它们在表面附近的积聚较少。在低振幅 EP 的作用下,粘附细菌的推进力和游动细菌的自适应逃逸能力都得到了增强。因此,低振幅和短持续时间的 EP 在可持续抗生物污染应用中大有可为。
{"title":"Adaptive Escape of <i>Pseudomonas aeruginosa</i> by Application of Low-Amplitude Electric Pulses.","authors":"Pu Feng, Jun Liu, Lian-Jun Bao, Eddy Y Zeng, Chunfeng Ma, Lingling Wang, Guangzhao Zhang, Xiangjun Gong","doi":"10.1021/acs.langmuir.4c00753","DOIUrl":"https://doi.org/10.1021/acs.langmuir.4c00753","url":null,"abstract":"<p><p>Marine antibiofouling using low-amplitude electric pulses (EP) is an energy-efficient and eco-friendly approach, but potential mechanisms for preventing biofouling remain unclear. In the present study, the 3D adhesion dynamics of a model microorganism─<i>Pseudomonas aeruginosa</i> (PAO1)─under low-amplitude cathodic EP were examined as a function of applying voltage and its duration (<i>t</i><sub>d</sub>). The results demonstrated that adhered bacteria escaped from the electrode surface even when EP was removed. The escaped bacteria ratio, induction period of escape, and duration of the detachment were influenced profoundly by EP amplitude but slightly by <i>t</i><sub>d</sub> when <i>t</i><sub>d</sub> ≥ 5 min. The acceleration of escaped PAO1 from the surface indicated that their flagellar motor was powered by EP. Particularly, EP enabled swimming bacteria to have adaptive motions that were sustainable and regulated by the gene <i>rsmA</i>. As a result, they had less accumulation near the surface. The propulsion of adhered bacteria and adaptive escape of swimming bacteria were enhanced in response to low-amplitude EP. Hence, low-amplitude and short-duration EP is promising for sustainable antibiofouling applications.</p>","PeriodicalId":50,"journal":{"name":"Langmuir","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532831","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}
Pub Date : 2024-07-05Epub Date: 2024-05-30DOI: 10.1021/acs.jproteome.4c00013
Irina Oganesyan, Timothy P Jenkins, Andreas H Laustsen, Renato Zenobi, Julian A Harrison
Investigating snake venom is necessary for developing new treatments for envenoming and harnessing the therapeutic potential that lies within venom toxins. Despite considerable efforts in previous research, several technical challenges remain for characterizing the individual components within such complex mixtures. Here, we present native and top-down mass spectrometry (MS) workflows that enable the analysis of individual venom proteins within complex mixtures and showcase the utility of these methodologies on King cobra (Ophiophagus hannah) venom. First, we coupled ion mobility spectrometry for separation and electron capture dissociation for charge reduction to resolve highly convoluted mass spectra containing multiple proteins with masses ranging from 55 to 127 kDa. Next, we performed a top-down glycomic analysis of a 25.5 kDa toxin, showing that this protein contains a fucosylated complex glycan. Finally, temperature-controlled nanoelectrospray mass spectrometry facilitated the top-down sequence analysis of a β-cardiotoxin, which cannot be fragmented by collisional energy due to its disulfide bond pattern. The work presented here demonstrates the applicability of new and promising MS methods for snake venom analysis.
{"title":"Streamlining the Analysis of Proteins from Snake Venom.","authors":"Irina Oganesyan, Timothy P Jenkins, Andreas H Laustsen, Renato Zenobi, Julian A Harrison","doi":"10.1021/acs.jproteome.4c00013","DOIUrl":"10.1021/acs.jproteome.4c00013","url":null,"abstract":"<p><p>Investigating snake venom is necessary for developing new treatments for envenoming and harnessing the therapeutic potential that lies within venom toxins. Despite considerable efforts in previous research, several technical challenges remain for characterizing the individual components within such complex mixtures. Here, we present native and top-down mass spectrometry (MS) workflows that enable the analysis of individual venom proteins within complex mixtures and showcase the utility of these methodologies on King cobra (<i>Ophiophagus hannah</i>) venom. First, we coupled ion mobility spectrometry for separation and electron capture dissociation for charge reduction to resolve highly convoluted mass spectra containing multiple proteins with masses ranging from 55 to 127 kDa. Next, we performed a top-down glycomic analysis of a 25.5 kDa toxin, showing that this protein contains a fucosylated complex glycan. Finally, temperature-controlled nanoelectrospray mass spectrometry facilitated the top-down sequence analysis of a β-cardiotoxin, which cannot be fragmented by collisional energy due to its disulfide bond pattern. The work presented here demonstrates the applicability of new and promising MS methods for snake venom analysis.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05Epub Date: 2024-05-29DOI: 10.1021/acs.jproteome.4c00187
Kerry A Ramsbottom, Ananth Prakash, Yasset Perez-Riverol, Oscar Martin Camacho, Zhi Sun, Deepti J Kundu, Emily Bowler-Barnett, Maria Martin, Jun Fan, Dmytro Chebotarov, Kenneth L McNally, Eric W Deutsch, Juan Antonio Vizcaíno, Andrew R Jones
Phosphorylation is the most studied post-translational modification, and has multiple biological functions. In this study, we have reanalyzed publicly available mass spectrometry proteomics data sets enriched for phosphopeptides from Asian rice (Oryza sativa). In total we identified 15,565 phosphosites on serine, threonine, and tyrosine residues on rice proteins. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation likely caused by different kinase groups. We cross-referenced phosphosites against the rice 3,000 genomes, to identify single amino acid variations (SAAVs) within or proximal to phosphosites that could cause loss of a site in a given rice variety and clustered the data to identify groups of sites with similar patterns across rice family groups. The data has been loaded into UniProt Knowledge-Base─enabling researchers to visualize sites alongside other data on rice proteins, e.g., structural models from AlphaFold2, PeptideAtlas, and the PRIDE database─enabling visualization of source evidence, including scores and supporting mass spectra.
{"title":"Meta-Analysis of Rice Phosphoproteomics Data to Understand Variation in Cell Signaling Across the Rice Pan-Genome.","authors":"Kerry A Ramsbottom, Ananth Prakash, Yasset Perez-Riverol, Oscar Martin Camacho, Zhi Sun, Deepti J Kundu, Emily Bowler-Barnett, Maria Martin, Jun Fan, Dmytro Chebotarov, Kenneth L McNally, Eric W Deutsch, Juan Antonio Vizcaíno, Andrew R Jones","doi":"10.1021/acs.jproteome.4c00187","DOIUrl":"10.1021/acs.jproteome.4c00187","url":null,"abstract":"<p><p>Phosphorylation is the most studied post-translational modification, and has multiple biological functions. In this study, we have reanalyzed publicly available mass spectrometry proteomics data sets enriched for phosphopeptides from Asian rice (<i>Oryza sativa</i>). In total we identified 15,565 phosphosites on serine, threonine, and tyrosine residues on rice proteins. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation likely caused by different kinase groups. We cross-referenced phosphosites against the rice 3,000 genomes, to identify single amino acid variations (SAAVs) within or proximal to phosphosites that could cause loss of a site in a given rice variety and clustered the data to identify groups of sites with similar patterns across rice family groups. The data has been loaded into UniProt Knowledge-Base─enabling researchers to visualize sites alongside other data on rice proteins, e.g., structural models from AlphaFold2, PeptideAtlas, and the PRIDE database─enabling visualization of source evidence, including scores and supporting mass spectra.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05Epub Date: 2024-05-31DOI: 10.1021/acs.jproteome.4c00010
Erin M Humphries, Dylan Xavier, Keith Ashman, Peter G Hains, Phillip J Robinson
High-throughput tissue proteomics has great potential in the advancement of precision medicine. Here, we investigated the combined sensitivity of trap-elute microflow liquid chromatography with a ZenoTOF for DIA proteomics and phosphoproteomics. Method optimization was conducted on HEK293T cell lines to determine the optimal variable window size, MS2 accumulation time and gradient length. The ZenoTOF 7600 was then compared to the previous generation TripleTOF 6600 using eight rat organs, finding up to 23% more proteins using a fifth of the sample load and a third of the instrument time. Spectral reference libraries generated from Zeno SWATH data in FragPipe (MSFragger-DIA/DIA-NN) contained 4 times more fragment ions than the DIA-NN only library and quantified more proteins. Replicate single-shot phosphopeptide enrichments of 50-100 μg of rat tryptic peptide were analyzed by microflow HPLC using Zeno SWATH without fractionation. Using Spectronaut we quantified a shallow phosphoproteome containing 1000-3000 phosphoprecursors per organ. Promisingly, clear hierarchical clustering of organs was observed with high Pearson correlation coefficients >0.95 between replicate enrichments and median CV of 20%. The combined sensitivity of microflow HPLC with Zeno SWATH allows for the high-throughput quantitation of an extensive proteome and shallow phosphoproteome from small tissue samples.
{"title":"High-Throughput Proteomics and Phosphoproteomics of Rat Tissues Using Microflow Zeno SWATH.","authors":"Erin M Humphries, Dylan Xavier, Keith Ashman, Peter G Hains, Phillip J Robinson","doi":"10.1021/acs.jproteome.4c00010","DOIUrl":"10.1021/acs.jproteome.4c00010","url":null,"abstract":"<p><p>High-throughput tissue proteomics has great potential in the advancement of precision medicine. Here, we investigated the combined sensitivity of trap-elute microflow liquid chromatography with a ZenoTOF for DIA proteomics and phosphoproteomics. Method optimization was conducted on HEK293T cell lines to determine the optimal variable window size, MS2 accumulation time and gradient length. The ZenoTOF 7600 was then compared to the previous generation TripleTOF 6600 using eight rat organs, finding up to 23% more proteins using a fifth of the sample load and a third of the instrument time. Spectral reference libraries generated from Zeno SWATH data in FragPipe (MSFragger-DIA/DIA-NN) contained 4 times more fragment ions than the DIA-NN only library and quantified more proteins. Replicate single-shot phosphopeptide enrichments of 50-100 μg of rat tryptic peptide were analyzed by microflow HPLC using Zeno SWATH without fractionation. Using Spectronaut we quantified a shallow phosphoproteome containing 1000-3000 phosphoprecursors per organ. Promisingly, clear hierarchical clustering of organs was observed with high Pearson correlation coefficients >0.95 between replicate enrichments and median CV of 20%. The combined sensitivity of microflow HPLC with Zeno SWATH allows for the high-throughput quantitation of an extensive proteome and shallow phosphoproteome from small tissue samples.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.
{"title":"Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.","authors":"Hui-Ping Shen, Xiaotao Dong, Zhi-Bin Li, Jing-Zhu Wu, Chun-Mei Zheng, Xie-Jun Hu, Chao Qian, Sheng-Pang Wang, Yu-Long Zhao, Ji-Cheng Li","doi":"10.1021/acs.jproteome.4c00040","DOIUrl":"10.1021/acs.jproteome.4c00040","url":null,"abstract":"<p><p>Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05Epub Date: 2024-06-13DOI: 10.1021/acs.joc.4c00570
Maryam Miri, Avat Arman Taherpour, Curt Wentrup
The formation and rearrangements of nitrile imines are of ongoing synthetic and theoretical interest. In this paper, we report a computational investigation at the M06/6-311 + G(d,p) level of the formation and rearrangement of propargylic N-phenyl-C-styrylnitrile imine 3 from 2-phenyl-5-styryltetrazole 1 by flash vacuum pyrolysis (FVP). Nitrile imine 3 cyclizes to 3aH-3-styrylindazole 4, which is also generated by H-shifts in the FVP of 3-styrylindazole 8. Tautomerization of 4 and N2-elimination afford cyclohexadienylidene 14, which by cyclization followed by H-shifts yields the primary pyrolysis product, 3-phenylindene 5. An alternate path via 7aH-3-styrylindazole, phenyl(styryl)diazomethane, and phenyl(styryl)carbene is potentially possible. The analogous pyrolysis of 2-phenyl-5-phenylethynyltetrazole 1' afforded cyclopenta[fg]fluorene and cyclopenta[def]phenanthrene via N-phenyl-C-phenylethynylnitrile imine 3' and 3aH-3-phenylethynylindazole 4'. In both cases, 3 and 3', rearrangement to diazocyclohexadienes and cyclohexadienylidenes (e.g., 14) is energetically preferred over alternate aryldiazomethane and arylcarbene intermediates.
{"title":"Nitrile Imine Cyclizations and Rearrangements: <i>N</i>-Phenyl-<i>C</i>-styrylnitrile Imine and <i>N</i>-Phenyl-<i>C</i>-phenylethynylnitrile Imine.","authors":"Maryam Miri, Avat Arman Taherpour, Curt Wentrup","doi":"10.1021/acs.joc.4c00570","DOIUrl":"10.1021/acs.joc.4c00570","url":null,"abstract":"<p><p>The formation and rearrangements of nitrile imines are of ongoing synthetic and theoretical interest. In this paper, we report a computational investigation at the M06/6-311 + G(d,p) level of the formation and rearrangement of propargylic <i>N-</i>phenyl<i>-C-</i>styrylnitrile imine <b>3</b> from 2-phenyl-5-styryltetrazole <b>1</b> by flash vacuum pyrolysis (FVP). Nitrile imine <b>3</b> cyclizes to 3a<i>H</i>-3-styrylindazole <b>4</b>, which is also generated by H-shifts in the FVP of 3-styrylindazole <b>8</b>. Tautomerization of <b>4</b> and N<sub>2</sub>-elimination afford cyclohexadienylidene <b>14</b>, which by cyclization followed by H-shifts yields the primary pyrolysis product, 3-phenylindene <b>5</b>. An alternate path via 7a<i>H</i>-3-styrylindazole, phenyl(styryl)diazomethane, and phenyl(styryl)carbene is potentially possible. The analogous pyrolysis of 2-phenyl-5-phenylethynyltetrazole <b>1'</b> afforded cyclopenta[<i>fg</i>]fluorene and cyclopenta[<i>def</i>]phenanthrene via <i>N</i>-phenyl-<i>C</i>-phenylethynylnitrile imine <b>3'</b> and 3a<i>H</i>-3-phenylethynylindazole <b>4'</b>. In both cases, <b>3</b> and <b>3'</b>, rearrangement to diazocyclohexadienes and cyclohexadienylidenes (e.g., <b>14</b>) is energetically preferred over alternate aryldiazomethane and arylcarbene intermediates.</p>","PeriodicalId":57,"journal":{"name":"The Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309640","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}
Pub Date : 2024-07-05Epub Date: 2024-06-17DOI: 10.1021/acs.jproteome.4c00339
Brooke M Harkness, Siting Chen, Kilsun Kim, Ashok P Reddy, Trevor J McFarland, Deborah M Hegarty, Steven J Everist, Julie A Saugstad, Jodi Lapidus, Anat Galor, Sue A Aicher
Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.
{"title":"Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.","authors":"Brooke M Harkness, Siting Chen, Kilsun Kim, Ashok P Reddy, Trevor J McFarland, Deborah M Hegarty, Steven J Everist, Julie A Saugstad, Jodi Lapidus, Anat Galor, Sue A Aicher","doi":"10.1021/acs.jproteome.4c00339","DOIUrl":"10.1021/acs.jproteome.4c00339","url":null,"abstract":"<p><p>Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (<i>n</i> = 16)] and patients with no pain [NRS ≤ 1 at 3 months (<i>n</i> = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05Epub Date: 2024-06-20DOI: 10.1021/acs.orglett.4c01783
Yubing Liu, Xun Zhang, Jie Li, Ao Kou, Hongxin Ding, Siping Pang, Chunlin He
Exploiting novel fused cyclic frameworks through simple and efficient methods has provided a blueprint for developing advanced explosives. In this study, six new [5,6,5]-tricyclic fused energetic compounds (I-VI) were synthesized through an intramolecular cyclization strategy involving a C-NH2 directed cyclization reaction. The work not only boosts the development of fused cyclic energetic compounds but also highlights their potential applications as secondary or heat-resistant explosives.
{"title":"An Intramolecular-Lock Facilitates Planar Tricyclic Fused Energetic Compounds.","authors":"Yubing Liu, Xun Zhang, Jie Li, Ao Kou, Hongxin Ding, Siping Pang, Chunlin He","doi":"10.1021/acs.orglett.4c01783","DOIUrl":"10.1021/acs.orglett.4c01783","url":null,"abstract":"<p><p>Exploiting novel fused cyclic frameworks through simple and efficient methods has provided a blueprint for developing advanced explosives. In this study, six new [5,6,5]-tricyclic fused energetic compounds (<b>I</b>-<b>VI</b>) were synthesized through an intramolecular cyclization strategy involving a C-NH<sub>2</sub> directed cyclization reaction. The work not only boosts the development of fused cyclic energetic compounds but also highlights their potential applications as secondary or heat-resistant explosives.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05Epub Date: 2024-06-20DOI: 10.1021/acs.orglett.4c02001
Runjie Xu, Yoichiro Kuninobu
We synthesized cyclic π-conjugated molecules by double Friedel-Crafts reaction of amino group-substituted 1,2-bis(2-phenylethynyl)benzene with Meldrum's acid derivative. The structures of the cyclic π-conjugated molecules were determined by single-crystal X-ray structure analysis. The oxidation of the dimethylamino group-substituted π-conjugated molecule with NOBF4 gave a closed-shell dication that is stable at >210 °C. The monoradical cation of the di(4-methoxyphenyl)amino group-substituted π-conjugated molecule is stable in dichloromethane solution (half-life of nearly 15 days) and shows near-infrared absorption.
{"title":"Synthesis and Properties of Cyclic π-Conjugated Molecules and Their Dication and Monoradical Cation.","authors":"Runjie Xu, Yoichiro Kuninobu","doi":"10.1021/acs.orglett.4c02001","DOIUrl":"10.1021/acs.orglett.4c02001","url":null,"abstract":"<p><p>We synthesized cyclic π-conjugated molecules by double Friedel-Crafts reaction of amino group-substituted 1,2-bis(2-phenylethynyl)benzene with Meldrum's acid derivative. The structures of the cyclic π-conjugated molecules were determined by single-crystal X-ray structure analysis. The oxidation of the dimethylamino group-substituted π-conjugated molecule with NOBF<sub>4</sub> gave a closed-shell dication that is stable at >210 °C. The monoradical cation of the di(4-methoxyphenyl)amino group-substituted π-conjugated molecule is stable in dichloromethane solution (half-life of nearly 15 days) and shows near-infrared absorption.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}