bluuebunny/crossref_metadata_2025 huggingface dataset:
CH Bond Functionalization by the Confluence of Organocatalysis and/or Transition Metal Catalysis with Photoredox Catalysis
Authors: Bhowmick Anindita , Behera Mousumi , Bhat Ramakrishna G.
Published: November 2022

Over the years, the visible‐light photoredox catalysis has gained a great interest and attention to achieve efficient and attractive strategies to construct useful organic scaffolds relatively more sustainable manner using a clean energy source. There has been a great focus on the CH bond functionalization via photoredox catalysis over the last few years owing to its atom‐ and step‐economical features. Recently, the merger of photoredox catalysis with transition metal catalysis or organocatalysis is emerging as a very powerful and promising tool to access useful molecules which otherwise were difficult via traditional approaches. This article highlights some of the recent advancements in the CH bond functionalization by the merger of photoredox catalysis with organocatalysis and/or transition metal catalysis, and some of the miscellaneous reactions of photoredox catalysis. This article also highlights the protocols based on dual catalysis using organic photoredox catalysts to avoid the metal catalysts. The strategic merging of photoredox catalysis with complementary activation modes of catalysis has successfully allowed the interesting transformations to construct useful compounds.
Gold‐Catalyzed C(sp
2
)H Bond Functionalization
Authors: Liu Xun‐Shen , Liu Lu
Published: November 2022

The direct conversion of CH bond into CX bond has been emergent as an efficient approach for the construction of complex molecules. In this area, gold‐catalyzed C(sp
2
)H bond functionalization has attracted great interest over the past two decades as a synthetic toolbox for the construction of complex molecules and late‐stage modification of bioactive compounds. This article summarizes the evolution of gold‐catalyzed C(sp
2
)H bond functionalization and exhibits the different chemo‐ and site‐selectivities under various reaction conditions.
Metal‐Free Oxidative CH Bond Functionalization
Authors: Dahatonde Dipak J. , Bisht Shweta , Batra Sanjay
Published: November 2022

Direct replacement of an inert CH bond with a functional group is traditionally termed CH bond functionalization. Remarkable progress in the strategies for CH functionalization has enabled organic chemists to take advantage of the ubiquity of the CH bond in the chemical feedstock to construct complex molecules. The CH bond functionalizations, resulting in a CC or C–hetero bond that is conventionally achieved via metal‐mediated activation of inert CH bond, are now of paramount importance in modern synthetic chemistry. However, growing environmental concerns and issues about sustainability have inspired the development of metal‐free approaches to such useful CH functionalization reactions under oxidative conditions. During the last decade, there has been profound progress in the development of a variety of innovative metal‐free oxidative CH functionalization reactions and this article presents the assimilation of the literature since 2015, concerning the construction of CC and C–hetero (N, O, S, Se, Te, P, B) bonds using the strategy.
Cobalt‐Catalyzed C(sp
2
)H Functionalizations
Authors: Zhai Hongbin , Qiu Shuxian , Zhai Shengxian , Wang Huifei
Published: November 2022

Cobalt catalysis has emerged as a powerful tool for the efficient and economic synthesis of numerous synthetic useful molecules in recent years. This chapter summarizes the recent progress and synthetic utility of cobalt catalysts toward C(sp
2
)H functionalization processes achieving CC bond formation, CX bond formation, and different types of annulations. And CH functionalizations by merging cobalt and photoredox catalysis or electro‐catalysis are also included.
Recent Advances in Palladium‐Based Cross‐Dehydrogenative‐Coupling (CDC) with C(sp
2
)H/C(sp
2
)H Bond to Form New C(sp
2
)C(sp
2
) Bond
Authors: Leung Man Pan , Tsang Yi Ling , Choy Pui Ying , Kwong Fuk Yee
Published: November 2022

The advancement of CH/CH cross‐dehydrogenative coupling (CDC) reactions for the construction of C(sp
2
)C(sp
2
) bond with representative examples from mainly 2016 to May 2021 is overviewed. Palladium‐catalyzed CDC reaction has been considered as a modern and attractive synthetic tool due to (i) limited amount of undesired and toxic by‐products; (ii) more straightforward synthetic approach from simple materials, resulting in a better step‐ and atom economy. Diversified applications across pharmaceutical and material areas have been successfully realized. In addition to the ordinary CDC reaction, the most recent accomplishments of asymmetric CDC process are also included.
Transition Metal‐Catalyzed CH Functionalization of Aldehydes
Authors: Wu Xianqing , Shrestha Mohini , Chen Yifeng
Published: November 2022

Aldehydes are ubiquitous and commercially available compounds with the characteristic of less toxicity and low cost. In the past decade, transition metal‐catalyzed cross‐coupling reactions have emerged as one of the most important tools for synthetic chemists to assemble various chemical bonds for the efficient construction of natural products and bioactive molecules. Recently, CH bond functionalization of aldehydes with manifold carbon coupling partners, catalyzed by different transition metals, has attracted growing attention as a straightforward and atom‐economical route to valuable ketone and ester synthesis. In this article, acylation of arene via selective CH activation will be briefly summarized. In addition, acylation of CX (X = halides, O, N, and metal) bond, recent hydroacylation, and carboacylation of unsaturated bond using aldehyde as an acyl surrogate will be mainly discussed.
Catalytic Aromatic CH Functionalization Involving Metal Carbene
Authors: Bao Ming , Huang Jingjing , Xu Xinfang
Published: November 2022

The metal carbene species, which catalytically generated from diazo compounds or other types of precursors, is one of the reactive and versatile synthons that possess broad applications in modern synthetic chemistry. A variety of reactions involving metal carbene have been well documented and reviewed, for example the metal carbene CH insertion reaction has become a very attractive and promising method for the expeditious construction of molecules with structural complexity. Whereas, reviews that focused on the catalytic aromatic CH functionalization using metal carbene, which went through a nondirected CH functionalization, are rare. This reaction has attracted considerable interest because of its ability for the direct CC bond formation with no need for prefunctionalization, providing a powerful and efficient tool in organic synthesis for rapid assembly of important molecules with structural diversity. The advances of catalytic aromatic CH functionalization using metal carbene in the last five decades using a variety of carbene precursors in the presence of different catalysts (or catalytic conditions), and the versatility of this method for the preparation of bioactive molecules, will be outlined in this article.
Sulfur (S)‐Directed CH Functionalization
Authors: Bao Rui‐Peng , Shao Nan‐Qi , Wang Fan , Wang Dong‐Hui
Published: November 2022

The uses of sulfur (S) atoms as the directing groups for the CH bond functionalization are summarized.
Alkynylation by Electrophilic CH Functionalization
Authors: Della‐Felice Franco , Montesinos‐Magraner Marc , Echavarren Antonio M.
Published: November 2022

The introduction of alkyne scaffolds in organic molecules is an interesting topic for researchers ranging from synthetic organic chemists to materials scientists. This goal can be achieved through very diverse disconnections strategies, among which the direct alkynylation of CH bonds is particularly appealing due to the broad scope of substrates that can be employed. In this article, we focus on electrophilic alkynylation methodologies, which employ haloalkynes and hypervalent iodine reagents as acetylene donors. As a result of the length constrains, methodologies based on radical mechanisms and those under oxidative conditions, including cross‐dehydrogenative couplings, are out of scope. The existing protocols for electrophilic alkynylation are herein described and organized by their undirected or directed character. For the latter, different sections were considered according to the nature of the directing group.
Organocatalytic Routes to CH Functionalization Reactions
Authors: Barik Shilpa , Biju Akkattu T.
Published: November 2022

Transition metal‐catalyzed reactions are powerful and routinely used for the functionalization of inert CH bonds. However, the toxicity of the metals, cost of the metal catalysts, and their availability limit the potential application of this strategy. Organocatalysis is an elegant alternative, and in few cases, provides reaction outcomes unparalleled in transition metal catalysis. The use of various organocatalytic techniques such as secondary amine catalysis,
N
‐heterocyclic carbene catalysis, H‐bonding catalysis, photoredox catalysis, etc. can be utilized for the transition metal‐free CH functionalization reactions. This article is aimed at highlighting the organocatalytic protocols for inert CH functionalization reactions (with selected examples) giving special emphasis on the catalytic mode of action and the type of inert CH bond being functionalized.
Deprotonative CH Zincation for Carbon–Carbon Bond Formation
Authors: Cho Seoyoung , Bitting Katie J. , Wang Qiu
Published: November 2022

This article focuses on the recent developments of deprotonative C

H zincation approaches for carbon–carbon bond formation as a useful strategy of C

H functionalization. Key to the success of this strategy is the development of different zincate bases for regioselective C

H zincation and subsequent coupling reactions of the generated organozinc intermediates with various partners. Herein presented are recent examples using deprotonative C

H zincation strategy for diverse carbon functionalization of Csp
3

H, Csp
2

H, and Csp

H bonds, including the installation of alkyl, alkenyl, alkynyl, aryl, and acyl groups, as well as zincation‐mediated multifunctionalization reactions in providing step‐efficient synthetic strategies.
Organocatalytic Allylic and Benzylic CH Bond Functionalization
Authors: Khuntia Rupkumar , Gharui Chandan , Pan Subhas C.
Published: November 2022

Selective functionalization of benzylic and allylic CH bonds has enormous effect in feedstock and fine chemistry. Conventional activation strategies of inert C(sp
3
)H bond usually require relatively harsh conditions. The most explored direction in the domain is transition metal catalysis, while organocatalysis is following behind. A joint force of organocatalysis and CH functionalization could be possible as they are coexisting and rapidly growing research fields in modern synthetic chemistry. This article summarizes the recent state of art in organocatalytic benzylic and allylic CH functionalization reactions for the formation of CC, CO, CN, CS, and Chalogen bonds. Diverse organocatalytic CH activation mechanisms have also been discovered in parallel with these studies, which complement or even bypass the prevalent transition metal catalysis.
Synthesis of Heteropolycyclic Aromatic Hydrocarbons Through Directed CH Functionalization
Authors: Biswal Pragati , Prusty Namrata , Ravikumar Ponneri C.
Published: November 2022

The increasing demand for polycyclic aromatic hydrocarbons (PAHs) as an advanced material led to significant interest among synthetic and material science community. PAHs being highly conjugated are found to have good absorption and emission properties. Heteropolycyclic aromatic hydrocarbons (hetero‐PAHs) are those with one or more heteroatoms in the carbon framework, and they have multifold applications in optoelectronics. Synthesis of such molecules via directed CH functionalization has reduced the time, energy, and more importantly multiple steps in comparison with their classical synthesis. In this article, the synthesis of these valuable doped‐PAHs/hetero‐PAHs through directed CH functionalization has been documented.
CH Functionalization‐Based Strategy in the Synthesis and Late‐Stage Modification of Drug and Bioactive Molecules
Authors: Wang Hua‐Nan , Bag Raghunath , Karuppu Selvaraj , Chen Gang , Xiao Guolan
Published: November 2022

CH functionalization approach is an attractive strategy in synthetic chemistry for the construction and diversification of bioactive drug molecules and their developments. Transition metal‐catalyzed CH activation, Minisci type radical reaction, and metal/organo‐photoredox‐catalyzed reactions are the hottest approaches, used in the organic chemist's toolbox for the rapid construction and late‐stage modification of functionalized bioactive scaffolds to achieve the desired drug research and development. In this aspect, the de novo synthesis has been utilized for the formation of drug molecules having new carbon–carbon and carbon–hetero bonds more efficiently within fewer steps via CH functionalization reactions. On the other hand, late‐stage functionalization is studied for the fast construction of highly diversified drug scaffolds without any kind of prefunctionalizations and has a major impact on drug discovery. In this article, we focus on the significant advances achieved in the CH functionalization‐based strategies including late‐stage methodology for the synthesis of selective drugs and drug‐like compounds found in academia as well as industry and showcase how the implementation of these modern strategies successfully accelerate the selectivity and efficiency in the drug discovery process to access new molecules of interest.
High‐Valent Oxomanganese Complexes of Relevance in Oxyfunctionalization of Hydrocarbons
Authors: Biswas Sachidulal , Biswas Achintesh N.
Published: November 2022

Selective activation of inert and ubiquitous CH bonds is one of the most challenging reactions in synthetic organic chemistry. Nature utilizes earth‐abundant paramagnetic metals to bind molecular oxygen and forms reactive high‐valent metal–oxo intermediates, which in turn, cleave strong CH bonds. A large number of biomimetic metal–oxo transients have been successfully synthesized in the last few decades, and many of these have shown promising reactivity toward oxyfunctionalization of hydrocarbons. The field is largely dominated by iron and manganese complexes supported by heme or nonheme ligands. Manganese, albeit of little significance in biological oxidation reactions, can generate high‐valent oxo transients to achieve stoichiometric and catalytic CH and CC activation. Reactivity studies in tandem with spectroscopic and computational analyses have endowed important insights onto the energetics of the oxomanganese transients. Oxidative reactivity of the high‐valent oxomanganese complexes has been shown to be influenced by secondary interactions, redox potentials, and metal–oxo basicity In this article, we highlight notable advances made in the high‐valent oxomanganese chemistry, with special emphasis on their reactivity in oxidation reactions, which include hydroxylation of alkanes and epoxidation of olefins.
Contemporary Concepts to Decipher the Reactivity of Paramagnetic Transition Metal Catalysts
Authors: Sen Asmita , Kumar Ravi , Rajaraman Gopalan
Published: November 2022

In the past few decades, the mechanistic features of various first‐row transition metal‐oxo dependent metalloenzymes and their biomimic models have been explored using various computational tools such as the density functional theory (DFT) and ab initio methods. The metalloenzymes and their synthetic analogs are capable of activating inert CH bonds of organic compounds. Over the years, a number of concepts have been developed in this area to understand their intriguing behavior. This includes two‐state reactivity (TSR), exchange enhance reactivity (EER), identical spin multistate reactivity (ISMR), quantum tunnelling and electronic cooperativity. Although these concepts are described individually in several studies, accumulative illustrations of these concepts with apt examples are lacking. In this article, we have attempted to address this issue and hope that bringing all these concepts under one roof can explain the CH bond activation of paramagnetic species in general and will be beneficial to the readers who are aiming to design such catalysts.
Merging Metal‐Catalyzed CH Activation Strategies and Renewable Energy Sources
Authors: Cembellín Sara
Published: November 2022

Transition metal‐catalyzed CH activation has become a powerful tool to create CC or CX bonds in organic molecules due to its multiple advantages such as the use of minimally prefunctionalized substrates, few steps, and potential for less waste. However, despite great progress in the area, many of these reactions still suffer from harsh conditions as they proceed at high temperatures or in the presence of toxic and expensive chemical oxidants. On the other hand, in recent years renewable energy sources have been introduced in organic chemistry offering a huge improvement in terms of sustainability. Specifically, the fields of photocatalysis and electrochemistry have experimented a real renaissance in the last decades, capable of developing eco‐friendly methodologies to prepare complex molecules from simple precursors. Thus, the combination of these technologies with metal‐catalyzed CH activation can represent an ideal solution in line with the principles of green chemistry, achieving challenging transformations under environmentally friendly conditions. Herein, the most important advances in this topic are described, highlighting representative examples of metallaelectro‐catalyzed and metallaphoto‐catalyzed CH activation reactions.
Activation of CH Bonds Through 1,
n
‐HAT (
n
= 4–8) Pathway
Authors: Tang Hai‐Tao , Chen Yue‐Min , Pan Ying‐Ming
Published: November 2022

The selective functionalization of inactive CH bonds is a subject of continuous exploration by synthetic organic chemists. Recent approaches relying on hydrogen atom transfer (HAT) processes have led to a tremendous revival in this field, due to the ability to activate inert CH bonds becoming more easily under mild conditions. HAT is applicable to a wider range of applications, possessing a higher tolerance of functional groups. Many synthetic methods based on HAT have been widely reported in the last few years. Recently, developments in mild methods for generating various central radicals have enabled them to be utilized in HAT processes, which in turn led to the development of remote C(sp
3
)H functionalization reactions for alcohols, amines, amides, and related compounds. This article mainly covers recent advances in 1,
n
‐HAT (
n
 = 4–8) methods involving photocatalytic, electrocatalytic, and metal‐catalytic approaches to CH functionalization reactions.
Iron Catalyzed CH Amination
Authors: Mukherjee Gourab , de Visser Sam P. , Sastri Chivukula V.
Published: November 2022

Due to its large natural abundance, iron is the metal that is often utilized by metalloenzymes in Nature. Their unique catalytic properties have triggered the interest of chemists and hence many studies have explored synthetic analogues, for instance, for CH activation reactions. Herein, we show a number of examples where we describe how different iron‐based catalysts undergo CH activation reactions. In particular, several highlights on the functions of iron in synthetic models of heme and non‐heme complexes are discussed. In these catalytic cycles the active form of iron is often in a high‐valent state that gives it its oxidative abilities. Specifically, bio‐inspired CH hydroxylation reactions are at the forefront of chemistry as conducted and catalyzed by a number of iron‐oxo systems that are synthesized and stabilized in a variety of ligand frameworks. In recent years; however, the isolobal analogue, namely the high‐valent iron‐imido complex, has been studied as well and found to be able to undergo CH activation of organic substrates. In this chapter, we have compiled a comparative analysis of iron‐oxo and imido systems towards CH activation reactions, and the factors governing such changes.
Mechanistic Studies on Cobalt‐Catalyzed, Bidentate Chelation‐Assisted CH Bond Functionalization
Authors: Lukasevics Lukass , Grigorjeva Liene
Published: November 2022

Over the last decade, cobalt‐catalyzed CH bond functionalization has proven to be a valuable tool for the synthesis of complex molecules. In particular, bidentate chelation‐assisted CH bond functionalization methodology has witnessed tremendous growth in a relatively short time, having numerous novel transformations developed for various substrate groups, utilizing a broad range of directing groups. Despite the progress made in this field, the understanding of mechanistic aspects for the transformations is not very well established as the majority of the proposed mechanisms rely on well‐studied mechanistic aspects of precious transition metals. As a consequence, only a few studies actually explain the catalyst's mode of action in depth based on meaningful mechanistic experiments and theoretical calculations. In this article, we summarize the current understanding of the mechanisms for cobalt‐catalyzed, bidentate chelation‐assisted CH bond functionalization with different coupling partners that are based either on experimental evidence or theoretical calculations.
Iron‐Catalyzed CH Bond Hydroxylation
Authors: Chatterjee Debasmita , Gupta Sayam Sen
Published: November 2022

Although Nature is using various metalloenzymes to functionalize CH bonds in ambient conditions, functionalization has always remained a challenge in synthetic chemistry. The most studied iron‐containing metalloenzymes are responsible to activate the CH bonds via high valent metal oxo species. Recognizing the ability of the natural metalloenzymes in unactivated CH bond activation scientists have indulged themselves in replicating the natural enzymatic process in laboratory. After decades of intense research, landmark discoveries have been achieved for mimicking both heme and non‐heme‐based iron‐containing catalyst system. In the early 2000s, simple Fe coordination complex [Fe(TPA)(CH
3
CN)
2
] emerged to be an effective model which can mimic the chemistry of nonheme oxygenases and catalyze a series of organic substrates. In the following years, the mechanistic framework studied for the system has provoked the thought of the development of a series of iron‐containing oxidation catalysts to perform selective functionalization of various organic substrates at ambient temperature and pressure. In this article, we will be discussing the evolution of iron‐based oxidation catalysts by highlighting the key design principles that enable the tuning of their reactivity and selectivity in the oxidation of CH bonds.
Effect of Information Content and General Practitioner Recommendation to Exercise on Treatment Beliefs and Intentions for Knee Osteoarthritis: An Online Multi‐Arm Randomized Controlled Trial
Authors: Lawford Belinda J. , Bennell Kim L. , Hall Michelle , Egerton Thorlene , McManus Fiona , Lamb Karen E. , Hinman Rana S.
Published: November 2022

Objective

To evaluate effects of general osteoarthritis (OA) information in addition to a treatment option grid and general practitioner (GP) recommendation to exercise on treatment beliefs and intentions.

Methods

An online randomized trial of 735 people 45 years old or older without OA who were recruited from a consumer survey network. Participants read a hypothetical scenario about visiting their GP for knee problems and were randomized to the following: i) ‘general information', ii) ‘option grid' (general information plus option grid), or iii) ‘option grid plus recommendation' (general information plus option grid plus GP exercise recommendation). The primary outcome was an agreement that exercise is the best management option (0‐10 numeric rating scale; higher scores indicating higher agreement that exercise is best). The secondary outcomes were beliefs about other management options and management intentions. Linear regression models estimated the mean (95% confidence interval [CI]) between‐group difference in postintervention scores, adjusted for baseline.

Results

Option grid plus recommendation led to higher agreement that exercise is the best management by a mean of 0.4 units (95% CI: 0.1‐0.6) compared with general information. There were no other between‐group differences for the primary outcome. Option grid led to higher agreement that surgery was best, and x‐rays were necessary, compared with general information (mean between‐group differences: 0.7 [CI: 0.2‐1.1] and 0.5 [CI: 0.1‐1.0], respectively) and option grid plus recommendation (0.5 [CI: 0.1‐0.9] and 0.9 [CI: 0.4‐1.3]).

Conclusion

Addition of an option grid and GP exercise recommendation to general OA information led to more favorable views that exercise was best for the hypothetical knee problem. However, differences were small and of unclear clinical importance.
Fault diagnosis by interval‐based adaptive thresholds and peak‐to‐peak observers
Authors: Ma Youdao , Wang Zhenhua , Meslem Nacim , Raïssi Tarek , Shen Yi
Published: November 2022

This article investigates actuator fault diagnosis for continuous‐time systems with unknown but bounded uncertainties. A novel interval‐based adaptive threshold computation approach is proposed for residual evaluation. Meanwhile, peak‐to‐peak performance is applied to generate robust residuals against system uncertainties. By integrating the designed peak‐to‐peak residual generator with adaptive thresholds, we can achieve promising fault detection results. Furthermore, based on the general observer scheme, the proposed residual generator and adaptive thresholds can be equally used for fault isolation. Simulation results are given to illustrate the effectiveness and superiority of the proposed fault detection and isolation method.
Efficient Inverted Perovskite Solar Cells via Improved Sequential Deposition
Authors: Chen Peng , Xiao Yun , Li Lei , Zhao Lichen , Yu Maotao , Li Shunde , Hu Juntao , Liu Bin , Yang Yingguo , Luo Deying , Hou Cheng‐Hung , Guo Xugang , Shyue Jing‐Jong , Lu Zheng‐Hong , Gong Qihuang , Snaith Henry J. , Zhu Rui
Published: November 2022

Inverted‐structure metal halide perovskite solar cells (PSCs) have attractive advantages like low‐temperature processability and outstanding device stability. The two‐step sequential deposition method shows the benefits of easy fabrication and decent performance repeatability. Nevertheless, it is still challenging to achieve high‐performance inverted PSCs with similar or equal power conversion efficiencies (PCEs) compared to the regular‐structure counterparts via this deposition method. Here, an improved two‐step sequential deposition technique is demonstrated via treating the bottom organic hole‐selective layer with the binary modulation system composed of a polyelectrolyte and an ammonium salt. Such improved sequential deposition method leads to the spontaneous refinement of up and buried interfaces for the perovskite films, contributing to high film quality with significantly reduced defect density and better charge transportation. As a result, the optimized PSCs show a large enhancement in the open‐circuit voltage by 100 mV and a dramatic lift in the PCE from 18.1% to 23.4%, delivering the current state‐of‐the‐art performances for inverted PSCs. Moreover, good operational and thermal stability is achieved upon the improved inverted PSCs. This innovative strategy helps gain a deeper insight into the perovskite crystal growth and defect modulation in the inverted PSCs based on the two‐step sequential deposition method.
Overcoming the Blood–Brain Barrier for Gene Therapy via Systemic Administration of GSH‐Responsive Silica Nanocapsules
Authors: Wang Yuyuan , Wang Xiuxiu , Xie Ruosen , Burger Jacobus C. , Tong Yao , Gong Shaoqin
Published: November 2022

CRISPR genome editing can potentially treat the root causes of many genetic diseases, including central nervous system (CNS) disorders. However, the promise of brain‐targeted therapeutic genome editing relies on the efficient delivery of biologics bypassing the blood–brain barrier (BBB), which represents a major challenge in the development of CRISPR therapeutics. We created and screened a library of glutathione (GSH)‐responsive silica nanocapsules (SNCs) for brain targeted delivery of biologics via systemic administration. In vivo studies demonstrate that systemically delivered SNCs conjugated with glucose and rabies virus glycoprotein peptide under glycemic control can efficiently bypass the intact BBB, enabling brain‐wide delivery of various biologics including CRISPR genome editors targeting different genes in both Ai14 reporter mice and wild‐type mice. In particular, up to 28% neuron editing via systemic delivery of Cre mRNA in Ai14 mice, up to 6.1% amyloid precursor protein (App) gene editing (resulting in 19.1% reduction in the expression level of intact APP), and up to 3.9% tyrosine hydroxylase (Th) gene editing (resulting in 30.3% reduction in the expression level of TH) in wild‐type mice are observed. This versatile SNC nanoplatform may offer a novel strategy for the treatment of CNS disorders including Alzheimer's, Parkinson's, and Huntington's disease.
Transparent Porous Conductive Substrates for Gas‐Phase Photoelectrochemical Hydrogen Production
Authors: Caretti Marina , Mensi Elizaveta , Kessler Raluca‐Ana , Lazouni Linda , Goldman Benjamin , Carbone Loï , Nussbaum Simon , Wells Rebekah A. , Johnson Hannah , Rideau Emeline , Yum Jun‐ho , Sivula Kevin
Published: November 2022

Gas diffusion electrodes are essential components of common fuel and electrolysis cells but are typically made from graphitic carbon or metallic materials, which do not allow light transmittance and thus limit the development of gas‐phase based photoelectrochemical devices. Herein, the simple and scalable preparation of F‐doped SnO2 (FTO) coated SiO2 interconnected fiber felt substrates is reported. Using 2–5 µm diameter fibers at a loading of 4 mg cm−2, the resulting substrates have porosity of 90%, roughness factor of 15.8, and Young's Modulus of 0.2 GPa. A 100 nm conformal coating of FTO via atmospheric chemical vapor deposition gives sheet resistivity of 20 ± 3 Ω sq−1 and loss of incident light of 41% at illumination wavelength of 550 nm. The coating of various semiconductors on the substrates is established including Fe2O3 (chemical bath deposition), CuSCN and Cu2O (electrodeposition), and conjugated polymers (dip coating), and liquid‐phase photoelectrochemical performance commensurate with flat FTO substrates is confirmed. Finally, gas phase H2 production is demonstrated with a polymer semiconductor photocathode membrane assembly at 1‐Sun photocurrent density on the order of 1 mA cm−2 and Faradaic efficiency of 40%.
In Response to Precision Medicine: Current Subcellular Targeting Strategies for Cancer Therapy
Authors: Li Zheng , Zou Jianhua , Chen Xiaoyuan
Published: November 2022

Emerging as a potent anticancer treatment, subcellular targeted cancer therapy has drawn increasing attention, bringing great opportunities for clinical application. Here, two targeting strategies for four main subcellular organelles (mitochondria, lysosome, endoplasmic reticulum, and nucleus), including molecule‐ and nanomaterial (inorganic nanoparticles, micelles, organic polymers, and others)‐based targeted delivery or therapeutic strategies, are summarized. Phototherapy, chemotherapy, radiotherapy, immunotherapy, and “all‐in‐one” combination therapy are among the strategies covered in detail. Such materials are constructed based on the specific properties and relevant mechanisms of organelles, enabling the elimination of tumors by inducing dysfunction in the corresponding organelles or destroying specific structures. The challenges faced by organelle‐targeting cancer therapies are also summarized. Looking forward, a paradigm for organelle‐targeting therapy with enhanced therapeutic efficacy compared to current clinical approaches is envisioned.
A Biobattery Capsule for Ingestible Electronics in the Small Intestine: Biopower Production from Intestinal Fluids Activated Germination of Exoelectrogenic Bacterial Endospores
Authors: Rezaie Maryam , Rafiee Zahra , Choi Seokheun
Published: November 2022

Functioning ingestible capsules offer tremendous promise for a plethora of diagnostic and therapeutic applications. However, the absence of realistic and practical power solutions has greatly hindered the development of ingestible electronics. Microbial fuel cells (MFCs) hold great potential as power sources for such devices as the small intestinal environment maintains a steady internal temperature and a neutral pH. Those conditions and the constant supply of nutrient‐rich organics are a perfect environment to generate long‐lasting power. Although previous small‐scale MFCs have demonstrated many promising applications, little is known about the potential for generating power in the human gut environment. Here, this work reports the design and operation of a microbial biobattery capsule for ingestible applications. Dormant Bacillus subtilis endospores are a storable anodic biocatalyst that will provide on‐demand power when revived by nutrient‐rich intestinal fluids. A conductive, porous, poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate hydrogel anode enables superior electrical performance in what is the world's smallest MFC. Moreover, an oxygen‐rich cathode maintains its effective cathodic capability even in the oxygen‐deficit intestinal environment. As a proof‐of‐concept demonstration in stimulated intestinal fluid, the biobattery capsule produces a current density of 470 µA cm−2 and a power density of 98 µW cm−2, ensuring its practical efficacy as a novel and sole power source for ingestible applications in the small intestine.
Microbiota attached to and encapsulated by granulomas dissected from tilapia spleen: A case report
Authors: Martínez‐Lara Pablo , Hernández‐López Jorge , Garibay‐Valdez Estefanía , Medina‐Félix Diana , Martínez‐Porchas Marcel , Coronado‐Molina Daniel , Ortiz‐Luna Romel J. , Puerto José H. , Gracia‐Valenzuela Martina Hilda
Published: November 2022

Granulomatous diseases are caused mainly by bacterial infections that the fish immune system cannot eliminate; consequently, pathogens are encapsulated, forming a complex structure where immune cells participate in containing the damage. The granuloma is covered by a collagenous layer that may be an attractive surface for external bacteria, leading to the potential development of a microbiota associated with the outer side of granulomas. Therefore, this study aimed to describe the microbiota attached to and encapsulated by granulomas dissected from tilapia spleen obtained from a commercial farm. Tissue samples with an advanced granulomatosis stage were analyzed by amplifying and sequencing the V4 variable region of the 16S rRNA gene. More than 20 phyla were detected attached to granulomas; however, only five represented 94% of the relative abundance, and the genus Gordonia was the most abundant with 21.9%. This bacterium has been previously identified in the tilapia gut and has also been reported as the etiologic agent of granulomatous disease in humans and terrestrial animals. This is the first time it has been detected in fish granulomas. Finally, these results provide the first evidence of microbiota attached to granulomatous lesions while demonstrating that these can provide a

surface that can harbour highly diverse microbial communities.
Conversion of Biomass‐derived Aldehydes using Environmentally Benign CuNi nanocatalyst
Authors: Choudhary Neha , Mobin Shaikh M.
Published: November 2022

In the present work, bimetallic CuNi‐12 (1 : 2 molar ratio of Cu : Ni) was synthesized via a liquid‐phase reduction method and utilized for the efficient and selective hydrogenation of biomass‐derived aldehydes and ketones with 2‐propanol as hydrogen source and KOH as base. The synergistic effect between copper and nickel metal enhanced the catalytic activity and selectivity. Bimetallic CuNi‐12 nanocatalyst is highly efficient and sustainable for converting various aldehyde and ketones with 100 % conversion and selectivity. Biomass derived alcohol i. e. furfural, cinnamaldehyde, 5‐hydroxy methyl furfural were utilized as substrate and converted into alcohol with 100 % conversion and selectivity. Bimetallic nanocatalyst CuNi‐12 having high surface area and it is reusable, magnetically separable and recyclable up to seven cycles.
Pathogen and Antibody Identification in Children with Encephalitis in Myanmar
Authors: Galardi Maria M. , Sowa Gavin M. , Crockett Cameron D. , Rudock Robert , Smith Alyssa E. , Shwe Ei E. , San Thidar , Linn Kyaw , Aye Aye Mya M. , Ramachandran Prashanth S. , Zia Maham , Wapniarski Anne E. , Hawes Isobel A. , Hlaing Chaw S. , Kyu Ei H. , Thair Cho , Mar Yi Y. , Nway Nway , Storch Gregory A. , Wylie Kristine M. , Wylie Todd N. , Dalmau Josep , Wilson Michael R. , Mar Soe S.
Published: November 2022

Objective

Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle‐income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar.

Methods

Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016–2018. Cohort 1 (n = 65) had locally available diagnostic testing, whereas cohort 2 (n = 38) had advanced tests for autoantibodies (ie, cell‐based assays, tissue immunostaining, studies with cultured neurons) and infections (ie, BioFire FilmArray multiplex Meningitis/Encephalitis multiplex PCR panel, metagenomic sequencing, and pan‐viral serologic testing [VirScan] of cerebrospinal fluid).

Results

A total of 20 cases (13 in cohort 1 and 7 in cohort 2) were found to have illnesses other than encephalitis. Of the 52 remaining cases in cohort 1, 43 (83%) had presumed infectious encephalitis, of which 2 cases (4%) had a confirmed infectious etiology. Nine cases (17%) had presumed autoimmune encephalitis. Of the 31 cases in cohort 2, 23 (74%) had presumed infectious encephalitis, of which one (3%) had confirmed infectious etiology using local tests only, whereas 8 (26%) had presumed autoimmune encephalitis. Advanced tests confirmed an additional 10 (32%) infections, 4 (13%) possible infections, and 5 (16%) cases of N‐methyl‐D‐aspartate receptor antibody encephalitis.

Interpretation

Pediatric encephalitis is prevalent in Myanmar, and advanced technologies increase identification of treatable infectious and autoimmune causes. Developing affordable advanced tests to use globally represents a high clinical and research priority to improve the diagnosis and prognosis of encephalitis. ANN NEUROL 2023;93:615–628
Room‐Temperature Spin Transport in Metal Nanocluster‐Based Spin Valves
Authors: Zhu Yanfei , Guo Lidan , Guo Jun , Zhao Luyang , Li Chunyan , Qiu Xueying , Qin Yang , Gu Xianrong , Sun Xiangnan , Tang Zhiyong
Published: November 2022

As a new type of inorganic‐organic hybrid semiconductor, quantum‐confined atomically precise metal nanoclusters (MNCs) have been widely applied in the fields of chemical sensing, optical imaging, biomedicine and catalysis. Herein, we successfully design and fabricate the first example of MNC‐based spin valves (SVs) that exhibit remarkable magnetoresistance (MR) value up to 1.6 % even at room temperature (300 K). The concomitant photoresponse of MNC‐based SVs unambiguously confirms that the spin‐polarized electron transmission takes place across the MNC interlayer. Furthermore, the spin‐dependent transport property of MNC‐based SVs is largely varied by changing the atomic structure of MNCs. Both experimental proofs and quantum chemistry calculations reveal that the atomic structure‐discriminative spin transport behavior is attributed to the distinct spin‐orbit coupling (SOC) effect of MNCs.
Engineering Hierarchical Recognition‐Mediated Senolytics for Reliable Regulation of Cellular Senescence and Anti‐Atherosclerosis Therapy
Authors: Xia Yinghao , Li Jili , Wang Linlin , Xie Yuqi , Zhang Lili , Han Xiaoyan , Tan Weihong , Liu Yanlan
Published: November 2022

Precise regulation of vascular senescence represents a far‐reaching strategy to combat age‐related diseases. However, the high heterogeneity of senescence, alongside the lack of targeting and potent senolytics, makes it very challenging. Here we report a molecular design to tackle this challenge through multidimensional, hierarchical recognition of three hallmarks commonly shared among senescence, namely, aptamer‐mediated recognition of a membrane marker for active cell targeting, a self‐immolative linker responsive to lysosomal enzymes for switchable drug release, and a compound against antiapoptotic signaling for clearance. Such senolytic can target and trigger severe cell apoptosis in broad‐spectrum senescent endothelial cells, and importantly, distinguish them from the quiescent state. Its potential for in vivo treatment of vascular diseases is successfully illustrated in a model of atherosclerosis, with effective suppression of the plaque progression yet negligible side effects.
A Petrochemical‐Free Route to Superelastic Hierarchical Cellulose Aerogel
Authors: Qin Bing , Yu Zhi‐Long , Huang Jin , Meng Yu‐Feng , Chen Rui , Chen Zhi , Yu Shu‐Hong
Published: November 2022

Cellulose aerogels are plagued by intermolecular hydrogen bond‐induced structural plasticity, otherwise rely on chemicals modification to extend service life. Here, we demonstrate a petrochemical‐free strategy to fabricate superelastic cellulose aerogels by designing hierarchical structures at multi scales. Oriented channels consolidate the whole architecture. Porous walls of dehydrated cellulose derived from thermal etching not only exhibit decreased rigidity and stickiness, but also guide the microscopic deformation and mitigate localized large strain, preventing structural collapse. The aerogels show exceptional stability, including temperature‐invariant elasticity, fatigue resistance (∼5 % plastic deformation after 105 cycles), high angular recovery speed (1475.4° s−1), outperforming most cellulose‐based aerogels. This benign strategy retains the biosafety of biomass and provides an alternative filter material for health‐related applications, such as face masks and air purification.
Copper Complexes with Diazoolefin Ligands and their Photochemical Conversion into Alkenylidene Complexes
Authors: Kooij Bastiaan , Varava Paul , Fadaei‐Tirani Farzaneh , Scopelliti Rosario , Pantazis Dimitrios A. , Van Trieste Gerard P. , Powers David C. , Severin Kay
Published: November 2022

Homometallic copper complexes with alkenylidene ligands are discussed as intermediates in catalysis but the isolation of such complexes has remained elusive. Herein, we report the structural characterization of copper complexes with bridging and terminal alkenylidene ligands. The compounds were obtained by irradiation of CuI complexes with N‐heterocyclic diazoolefin ligands. The complex with a terminal alkenylidene ligand required isolation in a crystalline matrix, and its structural characterization was enabled by in crystallo photolysis at low temperature.
Rhodium‐Catalyzed Remote Borylation of Alkynes and Vinylboronates
Authors: Zhang Minghao , Liu Zheming , Zhao Wanxiang
Published: November 2022

Remote functionalization involving a fascinating chain‐walking process has emerged as a powerful strategy for the rapid access to value‐added functional molecules from readily available feedstocks. However, the scope of current methods is predominantly limited to mono‐ and di‐substituted alkenes. The remote functionalization of multi‐ and heteroatom‐substituted alkenes is challenging, and the use of alkynes in the chain walking is unexplored. We herein report a rhodium catalyzed remote borylation of internal alkynes, offering an unprecedented reaction mode of alkynes for the preparation of synthetically valuable 1,n‐diboronates. The regioselective distal migratory hydroboration of sterically hindered tri‐ and tetra‐substituted vinylboronates is also demonstrated to furnish various multi‐boronic esters. Synthetic utilities are highlighted through the selective manipulation of the two boryl groups in products such as the regioselective cross coupling, oxidation, and amination.
Self‐Assembly of Helical Nanofibrous Chiral Covalent Organic Frameworks
Authors: Tang Xihao , Liao Xiangji , Cai Xinting , Wu Jialin , Wu Xueying , Zhang Qianni , Yan Yilun , Zheng Shengrun , Jiang Huawei , Fan Jun , Cai Songliang , Zhang Weiguang , Liu Yi
Published: November 2022

Despite significant progress on the design and synthesis of covalent organic frameworks (COFs), precise control over microstructures of such materials remains challenging. Herein, two chiral COFs with well‐defined one‐handed double‐helical nanofibrous morphologies were constructed via an unprecedented template‐free method, capitalizing on the diastereoselective formation of aminal linkages. Detailed time‐dependent experiments reveal the spontaneous transformation of initial rod‐like aggregates into the double‐helical microstructures. We have further demonstrated that the helical chirality and circular dichroism signal can be facilely inversed by simply adjusting the amount of acetic acid during synthesis. Moreover, by transferring chirality to achiral fluorescent molecular adsorbents, the helical COF nanostructures can effectively induce circularly polarized luminescence with the highest luminescent asymmetric factor (glum) up to ≈0.01.
Catalytic Living Ring‐Opening Metathesis Polymerization Using Vinyl Ethers as Effective Chain‐Transfer Agents
Authors: Mandal Ankita , Mandal Indradip , Kilbinger Andreas F. M.
Published: November 2022

A catalytic living ring‐opening metathesis copolymerization (ROMP) method is described that relies on a degenerative, reversible and regioselective exchange of propagating Fischer‐carbenes. All characteristics of a living polymerization such as narrow dispersity, excellent molar mass control and the ability to form block copolymers are achieved by this method. The method allows the use of up to 200 times less ruthenium complex than traditional living ROMP. We demonstrate the synthesis of ROMP‐ROMP diblock copolymers, ATRP from a ROMP macro‐initiator and living ROMP from a PEG‐based macro chain transfer agent. The cost‐effective, sustainable and environmentally friendly synthesis of degradable polymers and block copolymers enabled by this strategy will find various applications in biomedicine, materials science, and technology.
Aqueous Photoelectrochemical CO2Reduction to CO and Methanol over a Silicon Photocathode Functionalized with a Cobalt Phthalocyanine Molecular Catalyst
Authors: Shang Bo , Rooney Conor L. , Gallagher David J. , Wang Bernie T. , Krayev Andrey , Shema Hadar , Leitner Oliver , Harmon Nia J. , Xiao Langqiu , Sheehan Colton , Bottum Samuel R. , Gross Elad , Cahoon James F. , Mallouk Thomas E. , Wang Hailiang
Published: November 2022

We report a precious‐metal‐free molecular catalyst‐based photocathode that is active for aqueous CO2reduction to CO and methanol. The photoelectrode is composed of cobalt phthalocyanine molecules anchored on graphene oxide which is integrated via a (3‐aminopropyl)triethoxysilane linker to p‐type silicon protected by a thin film of titanium dioxide. The photocathode reduces CO2to CO with high selectivity at potentials as mild as 0 V versus the reversible hydrogen electrode (vs RHE). Methanol production is observed at an onset potential of −0.36 V vs RHE, and reaches a peak turnover frequency of 0.18 s−1. To date, this is the only molecular catalyst‐based photoelectrode that is active for the six‐electron reduction of CO2to methanol. This work puts forth a strategy for interfacing molecular catalysts to p‐type semiconductors and demonstrates state‐of‐the‐art performance for photoelectrochemical CO2reduction to CO and methanol.