Accounts of Chemical Research最新文献

Asymmetric catalytic radical reactions represent a powerful yet underexplored strategy for the efficient construction of chiral organic molecules. In this field, we have successfully integrated the advantages of electrosynthesis with chiral Lewis acid catalysis to establish an innovative outer-sphere catalytic mode based on chiral radical intermediates. The chiral Lewis acid catalyst activates carbonyl compounds to generate electron-rich enolate intermediates, thus lowering their oxidation potential while simultaneously generating key catalyst-associated radical intermediates under anodic oxidation. The Lewis acid-promoted electron transfer (LCET) mechanism inherently suppresses noncomplexed radical formation, resulting in minimal racemic background interference. Crucially, since the chiral catalyst is attached to the radical intermediate, the stereoselectivity can be modulated through rational ligand design, thereby achieving highly enantioselective radical transformations. This catalytic system is particularly noteworthy as the chiral catalyst engages in both the electron transfer process and stereoselective control. Based on this electrocatalytic platform, we have explored the reactivity of electrochemically generated chiral radical intermediates with various π-systems, including alkenes, alkynes, allenes, conjugated polyenes, and nitronate anions. These reactions consistently deliver excellent stereoselectivity to underscore the generality of this approach. This remarkable result has motivated us to further expand the scope of this strategy to develop asymmetric oxidative and dehydrogenative coupling reactions. Specifically, employing a nickel-bound α-carbonyl radical as a chiral template, we achieved reactions with diverse transient active intermediates, such as radicals and radical cation intermediates generated in situ under electrochemical conditions. Moreover, a new dual-catalytic electrochemical asymmetric system was developed to enable stereodivergent anodically oxidative homocoupling reactions for the predictable synthesis of all stereoisomers of the target molecule with precise control over both absolute and relative stereochemical configurations. The success of this electrocatalytic system demonstrates the synthetic potential of chiral radical intermediates while simultaneously opening new avenues for their application in the asymmetric and stereodivergent synthesis of complex molecular architectures. These advances establish a robust foundation for the advancement of enantioselective electrochemistry and highlight the considerable potential for broader application in synthetic methodologies.

The production of value-added chemicals from CO₂ has been a thriving topic of research for the past few decades because of its contribution to a circular carbon economy. Combined with CO₂ capture and storage, thermocatalytic hydrogenation of CO₂ to CH₃OH with green or blue hydrogen, offers an attractive route to mitigate CO₂ emissions and to decarbonize the chemical industry. Numerous studies have been focused on catalysts based on supported metallic nanoparticles; these catalysts consist of at least one transition or coinage metal and a promoter element combined with an oxide support to disperse the active phase. Besides Zn-promoters used in Cu-based hydrogenation catalysts, numerous reports point to Ga as a promoter for methanol synthesis. In recent years, Ga has been shown to convert almost all transition metals toward selective methanol synthesis, but its specific role remains a topic of discussions.

In this Account, we summarize how surface organometallic chemistry (SOMC) has enabled the discovery of novel catalysts and the development of detailed structure–activity relationships. Particularly, we show that Ga uniquely generates alloys with transition and coinage (Cu) metal elements across groups 8–11 and converts them into selective methanol synthesis catalysts. Specifically, we highlight the role of M–Ga alloy formation, alloy stability, and the formation of M(Ga)–GaO_x interfaces under reaction conditions. This has been possible thanks to the combination of SOMC, which enables the formation of supported nanoparticles with tailored compositions and interfaces, and state-of-the-art characterization including operando techniques along with computational modeling, including ab initio molecular dynamic calculations. Dynamic alloying–dealloying behaviors under reaction conditions and the formation of M/MGa–GaO_x interfaces are identified as key drivers for efficient methanol formation.

Reactive intermediates are valuable and intriguing in synthetic chemistry, but their high reactivity often makes them challenging to handle. Therefore, developing strategies to generate these species in a mild and controlled manner is crucial. One effective approach involves embedding the reactive intermediate within a molecular scaffold. Upon gentle heating, the scaffold undergoes fragmentation, liberating the desired intermediate. Ideally, the resulting byproducts are inert and do not participate in the subsequent reaction. Carpino’s hydrazine, H₂N₂A (A = C₁₄H₁₀ or anthracene), thus serves as an excellent scaffold candidate. By attaching a functional group of interest (E) to the hydrazine, the resulting compound EN₂A is expected to undergo fragmentation, releasing E, dinitrogen (N₂), and anthracene.

In this account, we describe our efforts to develop a series of molecular precursors featuring the composition EN₂A (E = C, CH₂, SO, RLB, and R₂B). These precursors are expected to be capable of releasing a single carbon atom, methylene, sulfur monoxide, borylene, and boryl anion, respectively. Interestingly, the fragmentation behavior of these hydrazine-based precursors is highly dependent on the substituents at nitrogen. For CN₂A, H₂CN₂A, and OSN₂A, the precursors are stable at room temperature. Meanwhile, for (RLB)N₂A, and (R₂B)N₂A, the precursors are transient intermediate and undergo anthracene extrusion even at low temperatures.

While the initial goal was to generate reactive species E, many cases have shown that free intermediates are not necessarily required for group transfer reactions. Instead, the hydrazine precursors often facilitate group transfer through highly selective, associative mechanisms (Type A). Additionally, the diazo intermediates formed via primary fragmentation are of particular interest, as they display reactivity analogous to diazoalkanes (R₂CN₂) or organic azides (RN₃, Type B). Notably, although hydrazine precursors, diazo intermediates, and low-valent species all participate in group transfer reactions, they exhibit distinct electronic structures. Consequently, their reactivity patterns and selectivity vary significantly, underscoring the diverse chemical space accessible through this versatile platform.

We believe that continued development of Carpino’s hydrazine derivatives holds significant potential for uncovering new reactive intermediates and gaining deeper mechanistic insights. Moreover, the reactivity demonstrated with boron may be extended to other main group elements, potentially enabling access to a broader class of compounds featuring terminal N₂ complexes.

Photoelectrochemical (PEC) systems are among the most promising solar-to-electrochemical energy conversion and storage technologies and are uniquely positioned to address global energy demand and environmental sustainability. Mimicking the essential functions of natural photosynthesis, including light harvesting, catalytic water oxidation, CO₂ reduction, and energy storage, requires materials that integrate efficient photon capture with rapid charge transport and robust catalytic activity. However, conventional photoelectrochemical materials are limited by the incomplete utilization of the solar spectrum and rapid charge recombination, leading to a narrowed redox potential window and compromised overall conversion efficiency. In this context, organic molecular PEC materials offer distinct advantages through their tunable, well-defined structures, enabling precise control over their electronic properties, redox behavior, and broad-spectrum light utilization. Integrating electron donor–acceptor (D–A) frameworks with redox-active or catalytic units into porous assemblies establishes spatially organized pathways for charge separation and catalytic transformation, although such a molecular-level design remains in its early stages. The central challenge lies in translating these structure–function insights into design principles that deliver multifunctional materials capable of controlled charge modulation, long-range electron transfer, and adaptive catalysis, thereby advancing the realization of complete artificial photosynthesis.

In this Account, we begin with decoding PEC systems through the design principles of molecular materials, emphasizing how molecular-level modifications influence key performance metrics. The main concept of developing molecular materials through molecular engineering for artificial photosynthesis, centered on PEC energy conversion and storage, is presented in this Account. It focuses on the state-of-the-art construction of efficient D–A structures by tuning functional groups and incorporating single and dual metals, with charge dynamics regulated by thermodynamic and kinetic processes. Advances and challenges in molecular engineering are highlighted, emphasizing that designing efficient D–A architectures requires the appropriate selection of molecular functional groups, tailored structures, and optimized properties, which are crucial for regulating long-lived charge separation states and driving diverse redox reactions in PEC systems. We outline best practices for designing and assembling coupled D–A architectures, highlighting our research contributions and the broader progress in solar-to-electrochemical energy conversion and storage during the past decade. The discussion further explores coupled/decoupled strategies, which offer solutions to challenges associated with solar-driven CO₂ splitting (for CO and O₂ generation), N₂ reduction (for NH₃ synthesis), a

Guanidine exhibits both similarities and differences compared to amines, endowing it with unique catalytic properties. The synthesis of chiral guanidine organocatalysts has garnered significant interest, focusing on three primary guanidine backbones: bicyclic, monocyclic, and open-chain structures. Acyclic guanidines, while more synthetically accessible than their cyclic counterparts, present challenges due to their flexible conformations and multiple substitution patterns. Moreover, the potential of chiral guanidine ligands in metal complex catalysis remains largely underexplored.

Our research group has been actively exploring chiral guanidine-amide-based asymmetric catalysis since 2009. The design strategy for these catalysts is rooted in the bifunctional capabilities of amino acids, which are easily functionalized into acyclic guanidine amides. These compounds incorporate new Brønsted base units and hydrogen bond donors. The readily tunable structure of guanidine amides allows five forms, including monoguanidine amide (GA), bisguanidine and its hemisalt (GB), guanidine sulfonamide (GC), hybrid guanidine amide–pyridine (GD), and quaternary guanidinium salt (QG). The applications of these compounds in asymmetric catalysis can be driven into four modes based on the role of guanidines: organocatalysis, organo-metal synergistic catalysis, guanidine/transition metal complex catalysis, and phase-transfer catalysis. First, as bifunctional organocatalysts through base/H-bond activation, guanidine derivatives have demonstrated exceptional diastereo- and enantioselectivity in a wide range of reactions including polar addition and cascades, cyclization, substitution, and insertion, etc. In these cases, abundant and labile H-bond interactions from both guanidine and amides account for the high diastereo- and enantioselectivity. Second, the combination of chiral guanidines with achiral dirhodium salts enabled synergistic catalysis to activate the reaction partners simultaneously, where the guanidine unit is disclosed as a proton shuttle or a chalcogen bond acceptor. Third, the copper complexes of guanidine amides and hybrid guanidines could promote both polar and radical reactions. The unique performance of these new catalysts lies in either bifunctional catalysis via a combination of metal coordination and H-bond assistance or rich electronic and coordination properties to leverage the redox ability of the catalytic species. In addition, the quaternary guanidinium salt has emerged as an effective bifunctional phase-transfer catalyst for tackling the challenging enantioselectivity issue in asymmetric α-aromatization of arynes.

In this Account, we recount the development of a series of chiral guanidine-amide-based organocatalysts and ligands derived from amino acids. Their applications are meticulously selected from a diverse array of asymmetric reactions, highlighting the evolution of their structures, f

Complex healthcare needs can be met through effective interprofessional collaboration. Since 2014, Swedish Child Healthcare Services (CHS) include universal team-based visits with a nurse and a physician who perform such visits at the age of 4 weeks, 6 months, 12 months, and 2.5 to 3 years, as well as targeted team-based visits to address additional needs. The aim of this study was to describe the prevalence of team-based visits in the Swedish CHS and possible associations between team-based visits and contextual factors that may affect its implementation. A national cross-sectional survey was conducted using a web-based questionnaire distributed to all reachable nurses, physicians, and psychologists (n =3,552) engaged in the CHS. Data were analyzed using descriptive statistics and binary and multivariate logistic regressions. The response rate was 32%. Team-based visits were reported by 82% of the respondents. For nurses and physicians, the most frequent indication was specific ages, while for psychologists it was to provide parental support. Respondents working at Family Centers were more likely to perform team-based visits in general, at 2.5 to 3 years and in case of additional needs, compared to respondents working at Child Health Centers (CHC) and other workplaces. In conclusion, team-based visits are well implemented, but the pattern differs depending on the contextual factors. Targeted team-based visits and team-based visits at the age of 2.5 to 3 years are most unequally implemented.

Children in low- and middle-income countries (LMIC) have high levels of unmet mental health needs, especially in disadvantaged communities. To address this gap, we developed a child mental health service improvement programme. This was co-facilitated using interprofessional principles and values in four countries, South Africa, Kenya, Turkey and Brazil. Eighteen stakeholders from different professions were interviewed after six months on their perspectives on enabling factors and challenges they faced in implementing service plans. Participants valued the holistic case management approach and scaled service model that underpinned the service plans. Emerging themes on participants' priorities related to service user participation, integrated care, and different levels of capacity-building. We propose that an integrated care model in LMIC contexts can maximize available resources, engage families and mobilize communities. Implementation requires concurrent actions at micro-, meso- and macro-level.

Isolated congenital anosmia (ICA) is a rare entity worldwide with poorly understood genetic variation. The diagnosis of ICA is made by exclusion of acquired causes of anosmia. Additionally, magnetic resonance imaging in ICA is essential for diagnosis, as it shows reduced or absent development of olfactory bulbs and shallow olfactory sulci. Here, we present the case of a 21-year-old man who presented to our clinic with complete anosmia since birth. The patient's history was negative for acquired causes of anosmia, and the physical examinations of the ears, nose, throat, head, and neck were all not remarkable. Smell testing revealed complete anosmia. The CT imaging was unremarkable; however, magnetic resonance imaging of the anterior brain and olfactory region showed bilaterally absent olfactory bulbs and olfactory tracts, with a shallow olfactory groove. The patient was then subjected to whole exome sequencing. Bioinformatics analysis was performed on the 37 genes associated with olfactory dysfunction, in which a missense variant was identified in the HS6ST1(NM_004807.3) gene was identified, which insilico tools predicted to be likely pathogenic. The results of this patient's genetic analysis add to the possible genetic culprits reported in ICA cases. Additional genetic analyses are required to validate mutations and understand the heterogeneity of disease representation.