Pub Date : 2025-03-01Epub Date: 2022-10-12DOI: 10.1177/0306624X221124853
Ayako Sasaki, Akemi Mochizuki, Daiki Yoshihara
The primary focus of this study was to explore the parenting attitudes that predict abusive parenting among incarcerated mothers in Japan. Data analyzed on 63 incarcerated mothers who had the legal custody of the youngest child revealed that belief in corporal punishment significantly predicted abusive parenting. The data further revealed that the impact of adverse childhood experiences and the parenting style of an intimate partner remained significant in predicting the risk of abusive parenting. These multiple risk factors affecting child abuse perpetration indicate the need to develop a multi-dimensional intervention in prison settings to address those multiple issues.
{"title":"Parenting Attitudes and Abusive Parenting among Incarcerated Mothers in Japan.","authors":"Ayako Sasaki, Akemi Mochizuki, Daiki Yoshihara","doi":"10.1177/0306624X221124853","DOIUrl":"10.1177/0306624X221124853","url":null,"abstract":"<p><p>The primary focus of this study was to explore the parenting attitudes that predict abusive parenting among incarcerated mothers in Japan. Data analyzed on 63 incarcerated mothers who had the legal custody of the youngest child revealed that belief in corporal punishment significantly predicted abusive parenting. The data further revealed that the impact of adverse childhood experiences and the parenting style of an intimate partner remained significant in predicting the risk of abusive parenting. These multiple risk factors affecting child abuse perpetration indicate the need to develop a multi-dimensional intervention in prison settings to address those multiple issues.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"317-335"},"PeriodicalIF":16.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33524531","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 : 2025-03-01Epub Date: 2022-09-01DOI: 10.1177/15347346221124239
Christos Argyriou, Nikolaos Papanas, George S Georgiadis
Diabetic foot ulcers remain difficult to heal, especially in the setting of peripheral arterial disease (PAD). Vascular surgeons are very important members of the multidisciplinary foot care team. To make the most of their potential, adequate education of vascular trainees on diabetic PAD remains a priority. This should include not only endovascular therapies but also open surgical approaches. Evaluation of trainees' skills, as well as of the educational program itself, is also desirable. Finally, simulation-based training may prove a useful educational tool.
糖尿病足溃疡仍然难以愈合，尤其是在患有外周动脉疾病（PAD）的情况下。血管外科医生是多学科足部护理团队中非常重要的成员。为了最大限度地发挥他们的潜力，当务之急是对血管外科医生学员进行有关糖尿病 PAD 的充分教育。这不仅应包括血管内疗法，还应包括开放手术方法。对受训者的技能以及教育项目本身进行评估也是可取的。最后，模拟培训可能会被证明是一种有用的教育工具。
{"title":"Diabetic Foot Management: Education of Vascular Surgeons Remains a Priority.","authors":"Christos Argyriou, Nikolaos Papanas, George S Georgiadis","doi":"10.1177/15347346221124239","DOIUrl":"10.1177/15347346221124239","url":null,"abstract":"<p><p>Diabetic foot ulcers remain difficult to heal, especially in the setting of peripheral arterial disease (PAD). Vascular surgeons are very important members of the multidisciplinary foot care team. To make the most of their potential, adequate education of vascular trainees on diabetic PAD remains a priority. This should include not only endovascular therapies but also open surgical approaches. Evaluation of trainees' skills, as well as of the educational program itself, is also desirable. Finally, simulation-based training may prove a useful educational tool.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"28-30"},"PeriodicalIF":16.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40341247","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 : 2025-03-01Epub Date: 2022-09-14DOI: 10.1177/15347346221126004
Eran Tamir, Aharon S Finestone, Yiftah Beer, Yoram Anekstein, Ran Atzmon, Yossi Smorgick
Minimally invasive floating metatarsal osteotomy is an option for treating neuropathic ulcers under the metatarsal heads. This study presents the radiographic results of the floating metatarsal osteotomy. We reviewed files and radiographs at least 4 months after a floating metatarsal osteotomy in patients with diabetic neuropathy. In 71 osteotomies in 54 patients with late onset diabetes (mean age 61 ± 9, mean HbA1c 7.9 ± 1.9%), the primary ulcer healed within 3.5 ± 1.4 weeks. Of 66 osteotomies where radiographs were available 10 had non-union (15%, all asymptomatic), 15 (23%) had hypertrophic callus formation and 41 (62%) had normal union. One patient developed an ulcer under the hypertrophic callus. This necessitated callus resection. Asymptomatic non-union may happen in 15% of floating osteotomies, but the osteotomies appear to be relatively safe and effective for neuropathic plantar metatarsal head ulcers. Hypertropic callus causing local re-ulceration is rare and can be managed surgically.
{"title":"Radiographic Bone Healing in Minimally Invasive Floating Metatarsal Osteotomy for Neuropathic Plantar Metatarsal Head Ulcers - A Retrospective Cohort Study.","authors":"Eran Tamir, Aharon S Finestone, Yiftah Beer, Yoram Anekstein, Ran Atzmon, Yossi Smorgick","doi":"10.1177/15347346221126004","DOIUrl":"10.1177/15347346221126004","url":null,"abstract":"<p><p>Minimally invasive floating metatarsal osteotomy is an option for treating neuropathic ulcers under the metatarsal heads. This study presents the radiographic results of the floating metatarsal osteotomy. We reviewed files and radiographs at least 4 months after a floating metatarsal osteotomy in patients with diabetic neuropathy. In 71 osteotomies in 54 patients with late onset diabetes (mean age 61 ± 9, mean HbA1c 7.9 ± 1.9%), the primary ulcer healed within 3.5 ± 1.4 weeks. Of 66 osteotomies where radiographs were available 10 had non-union (15%, all asymptomatic), 15 (23%) had hypertrophic callus formation and 41 (62%) had normal union. One patient developed an ulcer under the hypertrophic callus. This necessitated callus resection. Asymptomatic non-union may happen in 15% of floating osteotomies, but the osteotomies appear to be relatively safe and effective for neuropathic plantar metatarsal head ulcers. Hypertropic callus causing local re-ulceration is rare and can be managed surgically.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"219-224"},"PeriodicalIF":16.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40363451","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 : 2025-03-01Epub Date: 2022-11-03DOI: 10.1177/0306624X221133014
Katarzyna Czubak-Paluch, Małgorzata Łysiak
The world of people imprisoned in penitentiary institutions may never be understood by those who enjoy their freedom. The present study investigated the narratives about close relations, produced by inmates, with the analyses focusing specifically on the motive of power and the motive of intimacy, as described by McAdams. It was hypothesized that, depending on the length of prison sentence, the inmates would differ significantly regarding these motives and secondly that the motive of intimacy and the subjects' age would be significant predictors for the duration of the prison sentence. The study involved 356 male inmates (M = 28.80; SD = 10.91) who were asked to write stories about close relations with their partners. The findings show that individuals with longer prison sentence present a higher level of the power motive focused on building a stronger self, compared to the inmates sentenced to prison for a shorter duration. A multivariate regression analysis showed that the duration of imprisonment is positively predicted by the subjects' age and negatively by the motive of intimacy.
{"title":"Power and Intimacy Motives in Narratives About Closeness Presented by People Staying in a Penitentiary Institution.","authors":"Katarzyna Czubak-Paluch, Małgorzata Łysiak","doi":"10.1177/0306624X221133014","DOIUrl":"10.1177/0306624X221133014","url":null,"abstract":"<p><p>The world of people imprisoned in penitentiary institutions may never be understood by those who enjoy their freedom. The present study investigated the narratives about close relations, produced by inmates, with the analyses focusing specifically on the motive of power and the motive of intimacy, as described by McAdams. It was hypothesized that, depending on the length of prison sentence, the inmates would differ significantly regarding these motives and secondly that the motive of intimacy and the subjects' age would be significant predictors for the duration of the prison sentence. The study involved 356 male inmates (<i>M</i> = 28.80; <i>SD</i> = 10.91) who were asked to write stories about close relations with their partners. The findings show that individuals with longer prison sentence present a higher level of the power motive focused on building a stronger self, compared to the inmates sentenced to prison for a shorter duration. A multivariate regression analysis showed that the duration of imprisonment is positively predicted by the subjects' age and negatively by the motive of intimacy.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"336-351"},"PeriodicalIF":16.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464121","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 : 2025-03-01Epub Date: 2022-11-29DOI: 10.1007/s10354-022-00985-4
Christian Reiter
On the occasion of the reburial of Beethoven's mortal remains in 1863, skull fragments are said to have come into the possession of Prof. Dr. Seligmann, who was present at that time and had conducted scientific investigations. These fragments were inherited in his family and are currently housed in the USA. Their authenticity is doubted by some scientists. On the basis of a plaster cast of Beethoven's skull kept in the Natural History Museum, Fool's Tower, in Vienna, the exact topographical position of these skull fragments could be reconstructed and it could be shown that there is no indication that the fragments did not originate from Beethoven's skull.
{"title":"On the authenticity of Beethoven's skull fragments from the estate of Prof. Dr. Romeo Seligmann.","authors":"Christian Reiter","doi":"10.1007/s10354-022-00985-4","DOIUrl":"10.1007/s10354-022-00985-4","url":null,"abstract":"<p><p>On the occasion of the reburial of Beethoven's mortal remains in 1863, skull fragments are said to have come into the possession of Prof. Dr. Seligmann, who was present at that time and had conducted scientific investigations. These fragments were inherited in his family and are currently housed in the USA. Their authenticity is doubted by some scientists. On the basis of a plaster cast of Beethoven's skull kept in the Natural History Museum, Fool's Tower, in Vienna, the exact topographical position of these skull fragments could be reconstructed and it could be shown that there is no indication that the fragments did not originate from Beethoven's skull.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"52-59"},"PeriodicalIF":16.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40711452","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 : 2025-02-28DOI: 10.1021/acs.accounts.4c00800
Mei Hong
<p><p>ConspectusEnveloped viruses encode ion-conducting pores that permeabilize the host cell membranes and mediate the budding of new viruses. These viroporins are some of the essential membrane proteins of viruses, and have high sequence conservation, making them important targets of antiviral drugs. High-resolution structures of viroporins are challenging to determine by X-ray crystallography and cryoelectron microscopy, because these proteins are small, hydrophobic, and prone to induce membrane curvature. Solid-state NMR (ssNMR) spectroscopy is an ideal method for elucidating the structure, dynamics, and mechanism of action of viroporins in phospholipid membranes. This Account describes our investigations of influenza M2 proteins and the SARS-CoV-2 E protein using solid-state NMR.M2 proteins form acid-activated tetrameric proton channels that initiate influenza uncoating in the cell. <sup>15</sup>N and <sup>13</sup>C exchange NMR revealed that M2 shuttles protons into the virion using a crucial histidine, whose imidazole nitrogens pick up and release protons on the microsecond time scale at acidic pH. This proton exchange is synchronized with and facilitated by imidazole reorientation, which is observed in NMR spectra. Quantitative <sup>15</sup>N NMR spectra yielded the populations of neutral and cationic histidines as a function of pH, giving four proton dissociation constants (p<i>K</i><sub>a</sub>'s). The p<i>K</i><sub>a</sub>'s of influenza AM2 indicate that the +3 charged channel has the highest time-averaged single-channel conductance; thus the third protonation event defines channel activation. In comparison, influenza BM2 exhibits lower p<i>K</i><sub>a</sub>'s due to a second, peripheral histidine, which accelerates proton dissociation from the central proton-selective histidine. Amantadine binding to AM2 suppressed proton exchange and imidazole reorientation, indicating that this antiviral drug acts by inhibiting proton shuttling. Solid-state NMR <sup>13</sup>C-<sup>2</sup>H distance measurements revealed that amantadine binds the N-terminal pore of the channel near a crucial Ser31, whose mutation to asparagine causes amantadine resistance in circulating influenza A viruses. A second binding site, on the lipid-facing surface of the protein, only occurs when amantadine is in large excess in lipid bilayers. M2 not only functions as a proton channel but also conducts membrane scission during influenza budding in a cholesterol-dependent manner. Solid-state NMR distance experiments revealed that two cholesterol molecules bind asymmetrically to the surface of the tetrameric channel, thus recruiting the protein to the cholesterol-rich budding region of the cell membrane to cause membrane scission.To accelerate full structure determination of viroporins, we developed a suite of <sup>19</sup>F solid-state NMR techniques that measure interatomic distances to 1-2 nm. Using this approach, we determined the atomic structures of influenza BM2, SAR
{"title":"Solid-State NMR of Virus Membrane Proteins.","authors":"Mei Hong","doi":"10.1021/acs.accounts.4c00800","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00800","url":null,"abstract":"<p><p>ConspectusEnveloped viruses encode ion-conducting pores that permeabilize the host cell membranes and mediate the budding of new viruses. These viroporins are some of the essential membrane proteins of viruses, and have high sequence conservation, making them important targets of antiviral drugs. High-resolution structures of viroporins are challenging to determine by X-ray crystallography and cryoelectron microscopy, because these proteins are small, hydrophobic, and prone to induce membrane curvature. Solid-state NMR (ssNMR) spectroscopy is an ideal method for elucidating the structure, dynamics, and mechanism of action of viroporins in phospholipid membranes. This Account describes our investigations of influenza M2 proteins and the SARS-CoV-2 E protein using solid-state NMR.M2 proteins form acid-activated tetrameric proton channels that initiate influenza uncoating in the cell. <sup>15</sup>N and <sup>13</sup>C exchange NMR revealed that M2 shuttles protons into the virion using a crucial histidine, whose imidazole nitrogens pick up and release protons on the microsecond time scale at acidic pH. This proton exchange is synchronized with and facilitated by imidazole reorientation, which is observed in NMR spectra. Quantitative <sup>15</sup>N NMR spectra yielded the populations of neutral and cationic histidines as a function of pH, giving four proton dissociation constants (p<i>K</i><sub>a</sub>'s). The p<i>K</i><sub>a</sub>'s of influenza AM2 indicate that the +3 charged channel has the highest time-averaged single-channel conductance; thus the third protonation event defines channel activation. In comparison, influenza BM2 exhibits lower p<i>K</i><sub>a</sub>'s due to a second, peripheral histidine, which accelerates proton dissociation from the central proton-selective histidine. Amantadine binding to AM2 suppressed proton exchange and imidazole reorientation, indicating that this antiviral drug acts by inhibiting proton shuttling. Solid-state NMR <sup>13</sup>C-<sup>2</sup>H distance measurements revealed that amantadine binds the N-terminal pore of the channel near a crucial Ser31, whose mutation to asparagine causes amantadine resistance in circulating influenza A viruses. A second binding site, on the lipid-facing surface of the protein, only occurs when amantadine is in large excess in lipid bilayers. M2 not only functions as a proton channel but also conducts membrane scission during influenza budding in a cholesterol-dependent manner. Solid-state NMR distance experiments revealed that two cholesterol molecules bind asymmetrically to the surface of the tetrameric channel, thus recruiting the protein to the cholesterol-rich budding region of the cell membrane to cause membrane scission.To accelerate full structure determination of viroporins, we developed a suite of <sup>19</sup>F solid-state NMR techniques that measure interatomic distances to 1-2 nm. Using this approach, we determined the atomic structures of influenza BM2, SAR","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522087","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 : 2025-02-27DOI: 10.1021/acs.accounts.5c00024
Li Zhang, Fei-Yu Zhou, Lei Jiao
<p><p>ConspectusPyridine is a crucial heterocyclic compound in organic chemistry. Typically, the pyridine motif behaves as an N-nucleophile and an electron-deficient aromatic ring. Transforming the pyridine ring into an electron-rich system that exhibits reactivity contrary to classical expectations could unveil new opportunities in pyridine chemistry. This Account describes an approach to the umpolung reactivity of the pyridine ring through the formation of an unprecedented <i>N</i>-boryl pyridyl anion (<i>N</i>-BPA) intermediate that enables new catalysis and transformations.In 2017, we discovered that 4-phenylpyridine acts as an efficient catalyst for the borylation of iodo- and bromoarenes using diboron(4) compounds. Mechanistic studies revealed that the <i>in situ</i> formation of an <i>N</i>-BPA intermediate in the pyridine/diboron(4)/methoxide reaction system is a pivotal step in this transformation. Further investigations showed that <i>N</i>-BPA exhibits dual reactivities as both a strong electron donor and a potent nucleophile. This unique reactivity profile has unveiled novel pathways for redox catalysis, pyridine derivatizations, and umpolung transformations.Based on the electron-donor characteristic of the <i>N</i>-boryl pyridyl anion, we have developed a redox catalytic system mediated by a pyridine catalyst. In the pyridine/diboron(4)/base reaction system, the <i>in situ</i> formation of <i>N</i>-BPA followed by single electron transfer (SET) to a substrate with regeneration of the pyridine molecule establishes a redox catalytic cycle. This approach enables the single-electron reduction of a variety of substrates employing 4-phenylpyridine as a catalyst and diboron(4) as the electron source. Upon visible-light excitation, this intermediate transitions into its excited state, exhibiting significantly enhanced reductivity. This enables the establishment of a modular photoredox system consisting of various pyridine/diboron(4)/base combinations that allow for fine-tuning of its redox property. Using this strategy, we performed a series of challenging single-electron reduction reactions, including the single -electron reduction of nonactivated chloro- and fluoroarenes, and Birch reduction of arenes.The nucleophilic character of the <i>N</i>-boryl pyridyl anion was effectively harnessed to facilitate pyridine derivatization and umpolung transformations. By directly quenching the <i>in situ</i>-generated <i>N</i>-BPA with a proton source, we developed a practical approach to <i>N</i>-H-1,4-dihydropyridines (DHPs). Bimolecular nucleophilic substitution reaction between <i>N</i>-BPA and an alkyl bromide produced a 4-alkyl-1,4-DHP, which subsequently releases an alkyl radical under photoredox conditions. This process enabled a catalytic transformation of alkyl bromides into alkyl radicals. Employing 4-trifluoromethylpyridine in this chemistry, the resulting <i>N</i>-BPA intermediate undergoes elimination of fluoride to yield a 4-pyridyldiflu
{"title":"<i>N</i>-Boryl Pyridyl Anion Chemistry.","authors":"Li Zhang, Fei-Yu Zhou, Lei Jiao","doi":"10.1021/acs.accounts.5c00024","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00024","url":null,"abstract":"<p><p>ConspectusPyridine is a crucial heterocyclic compound in organic chemistry. Typically, the pyridine motif behaves as an N-nucleophile and an electron-deficient aromatic ring. Transforming the pyridine ring into an electron-rich system that exhibits reactivity contrary to classical expectations could unveil new opportunities in pyridine chemistry. This Account describes an approach to the umpolung reactivity of the pyridine ring through the formation of an unprecedented <i>N</i>-boryl pyridyl anion (<i>N</i>-BPA) intermediate that enables new catalysis and transformations.In 2017, we discovered that 4-phenylpyridine acts as an efficient catalyst for the borylation of iodo- and bromoarenes using diboron(4) compounds. Mechanistic studies revealed that the <i>in situ</i> formation of an <i>N</i>-BPA intermediate in the pyridine/diboron(4)/methoxide reaction system is a pivotal step in this transformation. Further investigations showed that <i>N</i>-BPA exhibits dual reactivities as both a strong electron donor and a potent nucleophile. This unique reactivity profile has unveiled novel pathways for redox catalysis, pyridine derivatizations, and umpolung transformations.Based on the electron-donor characteristic of the <i>N</i>-boryl pyridyl anion, we have developed a redox catalytic system mediated by a pyridine catalyst. In the pyridine/diboron(4)/base reaction system, the <i>in situ</i> formation of <i>N</i>-BPA followed by single electron transfer (SET) to a substrate with regeneration of the pyridine molecule establishes a redox catalytic cycle. This approach enables the single-electron reduction of a variety of substrates employing 4-phenylpyridine as a catalyst and diboron(4) as the electron source. Upon visible-light excitation, this intermediate transitions into its excited state, exhibiting significantly enhanced reductivity. This enables the establishment of a modular photoredox system consisting of various pyridine/diboron(4)/base combinations that allow for fine-tuning of its redox property. Using this strategy, we performed a series of challenging single-electron reduction reactions, including the single -electron reduction of nonactivated chloro- and fluoroarenes, and Birch reduction of arenes.The nucleophilic character of the <i>N</i>-boryl pyridyl anion was effectively harnessed to facilitate pyridine derivatization and umpolung transformations. By directly quenching the <i>in situ</i>-generated <i>N</i>-BPA with a proton source, we developed a practical approach to <i>N</i>-H-1,4-dihydropyridines (DHPs). Bimolecular nucleophilic substitution reaction between <i>N</i>-BPA and an alkyl bromide produced a 4-alkyl-1,4-DHP, which subsequently releases an alkyl radical under photoredox conditions. This process enabled a catalytic transformation of alkyl bromides into alkyl radicals. Employing 4-trifluoromethylpyridine in this chemistry, the resulting <i>N</i>-BPA intermediate undergoes elimination of fluoride to yield a 4-pyridyldiflu","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522069","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 : 2025-02-27DOI: 10.1021/acs.accounts.4c00846
Zengrui Cheng, Zhibin Hu, Ning Jiao
<p><p>ConspectusStable and inert C-C bonds form the fundamental framework of organic compounds. Consequently, direct transformations involving C-C bond cleavage present an innovative approach for the rapid modification and remodeling of molecular skeletons. In recent years, the concept of molecular skeletal editing has garnered widespread attention and has been significantly developed, providing new opportunities for the late-stage modification of bioactive molecules, the high-value transformation of bulk chemicals, and a revolution in the traditional fragment coupling strategies of chemical synthesis. Notable advancements in this field have focused on C-C bond cleavage and the remodeling of cyclic molecules, including ring expansion, ring contraction, and ring-opening reactions, thereby enriching the synthetic toolbox available to chemists. However, selective C-C bond transformation remains a formidable challenge, especially in the remodeling of complex molecules, due to the high bond dissociation energy and the difficulty in achieving precise selectivity control. Over the past few years, our group has made efforts to address these challenges. We have demonstrated the potential of cyclic molecule remodeling reactions as an efficient strategy for the synthesis and modification of complex molecules.Herein, we present two major thematic advancements achieved by our group, utilizing cascade activation and entropy-driven reconstruction strategies for molecular ring remodeling via C-C bond cleavage. These strategies are characterized by mild conditions, the accessibility of catalysts and reagents, and exceptional functional group compatibility, thereby emerging as novel approaches for molecular ring remodeling through atom-incorporation reactions mainly on nitrogenation, oxygenation, and halogenation to synthesize pharmaceuticals, natural products, and material molecules. (1) Ring expansion reactions: We developed novel reactions that enable the insertion of C-, N-, and O-containing units into molecular rings. These methodologies offer practical and efficient routes for synthesizing amides, amines, lactones, and nitrogen-containing heterocycles. (2) Ring-opening reactions: C-C bond cleavage in ring-opening reactions enables the efficient construction of distally difunctionalized molecular frameworks. By utilizing a transition metal catalysis and radical-mediated process, we have successfully achieved the cleavage of both C-C single bonds and C═C double bonds within molecular rings. Furthermore, we have tackled the highly challenging arene ring-opening (ARO) reaction, enabling the construction of stereoselective conjugated systems through the unsaturation liberation of aromatic systems. Mechanistic studies and DFT calculations have provided critical insights into these processes. We have also identified key intermediates involved in C-C bond cleavage, including benzyl azide, <i>O</i>-acetyl hydroxylamine, β-azido peroxyl radical, copper bisnitrene, and
{"title":"Molecular Ring Remodeling through C-C Bond Cleavage.","authors":"Zengrui Cheng, Zhibin Hu, Ning Jiao","doi":"10.1021/acs.accounts.4c00846","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00846","url":null,"abstract":"<p><p>ConspectusStable and inert C-C bonds form the fundamental framework of organic compounds. Consequently, direct transformations involving C-C bond cleavage present an innovative approach for the rapid modification and remodeling of molecular skeletons. In recent years, the concept of molecular skeletal editing has garnered widespread attention and has been significantly developed, providing new opportunities for the late-stage modification of bioactive molecules, the high-value transformation of bulk chemicals, and a revolution in the traditional fragment coupling strategies of chemical synthesis. Notable advancements in this field have focused on C-C bond cleavage and the remodeling of cyclic molecules, including ring expansion, ring contraction, and ring-opening reactions, thereby enriching the synthetic toolbox available to chemists. However, selective C-C bond transformation remains a formidable challenge, especially in the remodeling of complex molecules, due to the high bond dissociation energy and the difficulty in achieving precise selectivity control. Over the past few years, our group has made efforts to address these challenges. We have demonstrated the potential of cyclic molecule remodeling reactions as an efficient strategy for the synthesis and modification of complex molecules.Herein, we present two major thematic advancements achieved by our group, utilizing cascade activation and entropy-driven reconstruction strategies for molecular ring remodeling via C-C bond cleavage. These strategies are characterized by mild conditions, the accessibility of catalysts and reagents, and exceptional functional group compatibility, thereby emerging as novel approaches for molecular ring remodeling through atom-incorporation reactions mainly on nitrogenation, oxygenation, and halogenation to synthesize pharmaceuticals, natural products, and material molecules. (1) Ring expansion reactions: We developed novel reactions that enable the insertion of C-, N-, and O-containing units into molecular rings. These methodologies offer practical and efficient routes for synthesizing amides, amines, lactones, and nitrogen-containing heterocycles. (2) Ring-opening reactions: C-C bond cleavage in ring-opening reactions enables the efficient construction of distally difunctionalized molecular frameworks. By utilizing a transition metal catalysis and radical-mediated process, we have successfully achieved the cleavage of both C-C single bonds and C═C double bonds within molecular rings. Furthermore, we have tackled the highly challenging arene ring-opening (ARO) reaction, enabling the construction of stereoselective conjugated systems through the unsaturation liberation of aromatic systems. Mechanistic studies and DFT calculations have provided critical insights into these processes. We have also identified key intermediates involved in C-C bond cleavage, including benzyl azide, <i>O</i>-acetyl hydroxylamine, β-azido peroxyl radical, copper bisnitrene, and","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513979","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 : 2025-02-26DOI: 10.1021/acs.accounts.4c00854
Hong Lu, Jie Chang, Hao Wei
<p><p>Conspectus<i>N</i>-Heterocycles are essential in pharmaceutical engineering, materials science, and synthetic chemistry. Recently, skeletal editing, which involves making specific point changes to the core of a molecule through single-atom insertion, deletion, or transmutation, has gained attention for its potential to modify complex substrates. In this context, the insertion of nitrogen atoms into carbocycles to form <i>N</i>-heterocycles has emerged as a significant research focus in modern synthetic chemistry owing to its novel synthetic logic. This distinctive retrosynthetic approach enables late-stage modification of molecular skeletons and provides a different pathway for synthesizing multiply substituted <i>N</i>-heterocycles. Nevertheless, nitrogen atom insertion into carbocycles has proven challenging because of the inherent inertness of carbon-based skeletons and difficulty in cleaving C-C bonds. Therefore, selective insertion of nitrogen atoms for skeletal editing remains a challenging and growing field in synthetic chemistry. This Account primarily highlights the contributions of our laboratory to this active field and acknowledges the key contributions from other researchers. It is organized into two sections based on the type of the carbocycle. The first section explores the insertion of nitrogen atoms into cycloalkenes. Recent Co-catalyzed oxidative azidation strategies have enabled nitrogen atom insertion into cyclobutenes, cyclopentenes, and cyclohexenes, facilitating the synthesis of polysubstituted pyridines, which has been conventionally challenging through pyridine cross-coupling. The subsequent section highlights our discovery in the realm of nitrogen atom insertion into arenes. The site-selective skeletal editing of stable arenes is challenging in synthetic chemistry. We developed a method for the intramolecular insertion of nitrogen atoms into the benzene rings of 2-amino biaryls by suppressing the competing C-H insertion process by using a paddlewheel dirhodium catalyst. In addition, to address the challenging site-selective issues in nitrogen atom insertion, we employed arenols as substrates, which could act as selective controlling elements in site-selective skeletal editing. We reported a Cu-catalyzed nitrogen atom insertion into arenols, which proceeds through a dearomative azidation/aryl migration process, enabling the site-selective incorporation of nitrogen atoms into arenes. Inspired by this result, we recently extended the reaction model by using a Fe-catalyst to facilitate the ring contraction of the nitrogen-inserted product, achieving the carbon-to-nitrogen transmutation of arenols. Various complex polyaromatic arenols could effectively undergo the desired atom's transmutation, presenting considerable potential for various applications in materials chemistry. In this Account, we present an overview of our achievements in nitrogen atom insertion reactions, with a focus on the reaction scopes, mechanistic
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Pub Date : 2025-02-26DOI: 10.1021/acs.accounts.5c00013
Qi-Jun Yao, Bing-Feng Shi
<p><p>ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, and environmentally friendly 3d metals poses substantial challenges, primarily due to the variable oxidation states, intricate coordination patterns, and limited mechanistic insights. In this Account, we summarize our research endeavors in the development of three novel types of Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, <i>in situ</i>-generated chiral octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) catalysis, and Co(II)/chiral phosphoric acid (CPA) cooperative catalysis, achieved through strategic chiral ligand design. Our initial objective was to achieve enantioselective C-H functionalization catalyzed by achiral Cp*Co(III) catalysts with external chiral ligands, aiming to circumvent the laborious preparation of chiral Cp<sup><i>x</i></sup>Co(III) complexes. To this end, we developed several CCA ligands, incorporating non-covalent interactions (NCIs) as a crucial design element. Next, to address the limitations associated with the lengthy synthesis of Cp-ligated Co(III) complexes and the difficulties of modification, we explored the concept of the <i>in situ</i> generation of Co(III) catalysis using commercially available cobalt(II) salts with tailor-made chiral ligands. This exploration led to the development of two innovative catalytic systems, namely, Co(II)/Salox catalysis and Co(II)/CCA sequential catalysis. The Co(II)/Salox catalysis emerged as a versatile strategy, demonstrating excellent enantioselectivities across a range of asymmetric C-H functionalization reactions to construct various chiral molecules with central, axial, planar, and inherent chirality. The facile synthesis in a single step, along with ease of modification, further enhances the versatility and applicability of this approach. Moreover, we successfully applied cobalt/Salox catalysis in electro- and photochemical-catalyzed enantioselective C-H functionalization, using electrons or oxygen as traceless oxidant, thereby eliminating the need for stoichiometric chemical oxidants. Through mechanistic studies and reaction developments, we elucidated the detailed ligand structure-enantioselectivity relationships in cobalt/Salox catalysis, which are expected to inform future research endeavors. Finally, the Co(II)/CPA cooperative catalysis enabled the synthesis of chiral spiro-γ-lactams through sequential C-H olefination/asymmetric [4 + 1] spirocyclization. Mechanistically, the establishment of stereochemistry occurs during the cyclization step, where the CPA ligand serves as both a neutral ligand and a chiral Brønsted acid, with stereoinduction independent of the C-H cleavage step. We anticipate that the insights and advancements detailed in this Account will inspire further innovations in ligand deve
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