bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract

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

ObjectiveTo 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.MethodsAn 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.ResultsOption 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]).ConclusionAddition 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

SummaryThis 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

AbstractInverted‐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

AbstractCRISPR 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

AbstractGas 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

AbstractEmerging 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

AbstractFunctioning 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

AbstractGranulomatous 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 asurface that can harbour highly diverse microbial communities.