RESUMO
Computational organic chemistry has become a valuable tool in the field of bioorthogonal chemistry, offering insights and aiding in the progression of this branch of chemistry. In this review, I present an overview of computational work in this field, including an exploration of both the primary computational analysis methods used and their application in the main areas of bioorthogonal chemistry: (3 + 2) and [4 + 2] cycloadditions. In the context of (3 + 2) cycloadditions, detailed studies of electronic effects have informed the evolution of cycloalkyne/1,3-dipole cycloadditions. Through computational techniques, researchers have found ways to adjust the electronic structure via hyperconjugation to enhance reactions without compromising stability. For [4 + 2] cycloadditions, methods such as distortion/interaction analysis and energy decomposition analysis have been beneficial, leading to the development of bioorthogonal reactants with improved reactivity and the creation of orthogonal reaction pairs. To conclude, I touch upon the emerging fields of cheminformatics and machine learning, which promise to play a role in future reaction discovery and optimization.
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Reação de Cicloadição , Química Orgânica/métodos , Química Computacional , Aprendizado de MáquinaRESUMO
Natural products are substances found in nature that have not been significantly modified by humans [...].
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Produtos Biológicos , Humanos , Produtos Biológicos/farmacologia , Química OrgânicaRESUMO
A simple, reliable, and efficient method for the gram-scale chemical synthesis of pyrimidine nucleosides functionalized with C5-carboxyl, nitrile, ester, amide, or amidine, starting from unprotected uridine and cytidine, is described. The protocol involves the synthesis of 5-trifluoromethyluridine and 5-trifluoromethylcytidine with Langlois reagent (CF3 SO2 Na) in the presence of tert-butyl hydroperoxide and subsequent transformation of the CF3 group to the C5-C 'carbon substituents' under alkaline conditions. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Synthesis and characterization of 5-trifluoromethyluridine (5-CF3 U) and 5-trifluoromethylcytidine (5-CF3 C) Basic Protocol 2: Conversion of 5-CF3 U and 5-CF3 C to several C5-substituted ribonucleosides.
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Química Orgânica , Nucleosídeos de Pirimidina , Citidina/análogos & derivados , Nucleosídeos de Pirimidina/síntese química , Nucleosídeos de Pirimidina/química , Ribonucleosídeos/química , Uridina/análogos & derivados , Química Orgânica/métodosRESUMO
ABSTRACT: In this commentary, the authors explore the tension of balancing high performance standards in medical education with the acceptability of those standards to stakeholders (e.g., learners and patients). The authors then offer a lens through which this tension might be considered and ways forward that focus on both patient outcomes and learner needs.In examining this phenomenon, the authors argue that high performance standards are often necessary. Societal accountability is key to medical education, with the public demanding that training programs prepare physicians to provide high-quality care. Medical schools and residency programs, therefore, require rigorous standards to ensure graduates are ready to care for patients. At the same time, learners' experience is important to consider. Making sure that performance standards are acceptable to stakeholders supports the validity of assessment decisions.Equity should also be central to program evaluation and validity arguments when considering performance standards. Currently, learners across the continuum are variably prepared for the next phase in training and often face inequities in resource availability to meet high passing standards, which may lead to learner attrition. Many students who face these inequities come from underrepresented or disadvantaged backgrounds and are essential to ensuring a diverse medical workforce to meet the needs of patients and society. When these students struggle, it contributes to the leaky pipeline of more socioeconomically and racially diverse applicants.The authors posit that 4 key factors can balance the tension between high performance standards and stakeholder acceptability: standards that are acceptable and defensible, progression that is time variable, requisite support structures that are uniquely tailored for each learner, and assessment systems that are equitably designed.
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Química Orgânica , Educação Médica , Humanos , Estudantes , Avaliação de Programas e Projetos de Saúde , Pessoal de SaúdeRESUMO
The discovery of new glycosylation reactions is still a major challenge in carbohydrate chemistry. Traditional glycosylation reactions require the preparation of sugar donors with anomeric active or latent leaving groups. Dehydrative glycosylation is a fascinating alternative that enables the direct formation of the glycosidic bond from the hemiacetal, eliminating the need for (sometimes unstable) leaving groups, and allowing to reduce reaction, work-up, and purification times. Although some interesting methods of dehydrative glycosylation have been reported, in order to compete with conventional chemical glycosylation, a greater number of efficient and stereoselective methods need to be developed. Herein, a dehydrative procedure that uses a combination of iodine, triphenylphosphine, and a base (DMAP or imidazole) is described. This methodology allows for the preparation of sugar derivatives from commercially available 1-hydroxy glycosyl donors. The reaction takes place under mild conditions through the in situ-formation of an anomeric iodide intermediate, which, upon reaction with an alcohol, gives the corresponding glycosides up to quantitative yields and with high α-stereoselectivity.
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Iodo , Glicosilação , Compostos Organofosforados , Química Orgânica , GlicosídeosRESUMO
The chemistry of natural compounds inspired and still guides several branches of modern chemical sciences [...].
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Produtos Biológicos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Química OrgânicaRESUMO
Invited for the cover of this issue is the group of Prof. Xiaoming Wang at the Shanghai Institute of Organic Chemistry and Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences. The image depicts a combination of relay and cooperative catalysis with a triple iridium-photoredox-organocatalysis system to achieve an unprecedented reductive boration of amides. Read the full text of the article at 10.1002/chem.202301199.
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Amidas , Química Orgânica , China , Catálise , IrídioRESUMO
Living systems are composed of a complex network of bioactive small molecules, proteins, ions and electrons, which present a wealth of opportunities for researchers to explore. Recently, organic chemists have developed a keen interest to move chemical reactions from laboratory flasks into living systems. This offers a new avenue for addressing challenges in current organic chemistry, expands the range of chemical transformations accessible to living systems, and provides a versatile tool for understanding and manipulating living systems. In this tutorial review, we include both the fundamental mechanisms and specific examples of how chemical reactions that typically occur outside of the biological context can be adapted for use within living systems. We also highlight the use of the resulting functional organic materials for biomedical applications including but not limited to imaging, therapy, theranostics and organic electronics. Finally, we discuss current challenges and future perspectives in this exciting field. We envision this tutorial review will serve as a guide for designing new chemical reactions and pathways in living systems that can expand the range of biological processes and functions and will accelerate the development of new biomaterials, biocatalysts, and therapeutics for precision medicine and other social needs.
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Química Orgânica , Proteínas , Proteínas/química , EletrônicaRESUMO
The Nobel Prize Winner (1931) Dr. Otto H. Warburg had established that the primary energy source of the cancer cell is aerobic glycolysis (the Warburg effect). He also postulated the hypothesis about "the prime cause of cancer", which is a matter of debate nowadays. Contrary to the hypothesis, his discovery was recognized entirely. However, the discovery had almost vanished in the heat of battle about the hypothesis. The prime cause of cancer is essential for the prevention and diagnosis, yet the effects that influence tumor growth are more important for cancer treatment. Due to the Warburg effect, a large amount of data has been accumulated on biochemical changes in the cell and the organism as a whole. Due to the Warburg effect, the recovery of normal biochemistry and oxygen respiration and the restoration of the work of mitochondria of cancer cells can inhibit tumor growth and lead to remission. Here, we review the current knowledge on the inhibition of abnormal glycolysis, neutralization of its consequences, and normalization of biochemical parameters, as well as recovery of oxygen respiration of a cancer cell and mitochondrial function from the point of view of classical biochemistry and organic chemistry.
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Química Orgânica , Neoplasias , Humanos , Glicólise/fisiologia , Metabolismo Energético , Neoplasias/terapia , Neoplasias/patologia , OxigênioRESUMO
Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs.
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Antineoplásicos , Descoberta de Drogas , Análise Custo-Benefício , Técnicas de Química Combinatória , Química Orgânica , Antineoplásicos/uso terapêuticoRESUMO
Ionic liquids are used in various fields due to their unique physical properties and are widely utilized as reaction solvents in the field of synthetic organic chemistry. We have previously proposed a new organic synthetic method in which the catalyst and reaction reagents are supported on ionic liquids. This method has various advantages, such as the ability to reuse the reaction solvent and catalyst and its facile post-reaction treatment. In this paper, we describe the synthesis of an ionic liquid-supported anthraquinone photocatalyst and the synthesis of benzoic acid derivatives using this system. This synthesis of benzoic acid derivatives via the cleavage of vicinal diols by an ionic liquid-supported anthraquinone photocatalyst is an environmentally friendly process, and furthermore, it has a simple post-reaction process, and the catalyst and solvent can both be reused. To the best of our knowledge, this is the first report on the synthesis of benzoic-acid derivatives via the cleavage of vicinal diols using light and an ionic-liquid-supported catalyst.
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Líquidos Iônicos , Líquidos Iônicos/química , Solventes , Oxirredução , Química Orgânica/métodos , CatáliseRESUMO
A series of luminescent, neutral pentacoordinate dithieno[3,2-b:2',3'-d]phosphole compounds was synthesized by [4+1] cycloaddition of o-quinones with the corresponding trivalent phospholes. The electronic and geometrical modification of the π-conjugated scaffold implemented here impacts the aggregation behavior of the species in solution. It proved successful in generating species with improved Lewis acidity of the phosphorus center that was then leveraged for small-molecule activation. Hydride abstraction from an external substrate involving the hypervalent species is followed by an intriguing P-mediated umpolung from the hydride to a proton and supports the catalytic potential of this class of main-group Lewis acids for organic chemistry. This study is a comprehensive investigation into various methods, including electronic, chemical, geometric modifications (and sometimes combinations of these approaches) to systematically improve the Lewis acidity of neutral and stable main-group Lewis acids with practical value for a range of chemical transformations.
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Química Orgânica , Ácidos de Lewis , Catálise , Formação de Conceito , Reação de CicloadiçãoRESUMO
Organic chemistry has seen colossal progress due to machine learning (ML). However, the translation of artificial intelligence (AI) into materials science is challenging, where biological behavior prediction becomes even more complicated. Nanotoxicity is a critical parameter that describes their interaction with the living organisms screened in every bio-related research. To prevent excessive experiments, such properties have to be pre-evaluated. Several existing ML models partially fulfill the gap by predicting whether a nanomaterial is toxic or not. Yet, this binary categorization neglects the concentration dependencies crucial for experimental scientists. Here, an ML-based approach is proposed to the quantitative prediction of inorganic nanomaterial cytotoxicity achieving the precision expressed by 10-fold cross-validation (CV) Q2 = 0.86 with the root mean squared error (RMSE) of 12.2% obtained by the correlation-based feature selection and grid search-based model hyperparameters optimization. To provide further model flexibility, quantitative atom property-based nanomaterial descriptors are introduced allowing the model to extrapolate on unseen samples. Feature importance is calculated to find an interpretable model with optimal decision-making. These findings allow experimental scientists to perform primary in silico candidate screening and minimize the number of excessive, labor-intensive experiments enabling the rapid development of nanomaterials for medicinal purposes.
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Inteligência Artificial , Nanoestruturas , Aprendizado de Máquina , Química Orgânica , Sistemas Computacionais , Nanoestruturas/toxicidadeRESUMO
Over the past 20 years, the field of polymer mechanochemistry has amassed a toolbox of mechanophores that translate mechanical energy into a variety of functional responses ranging from color change to small-molecule release. These productive chemical changes typically occur at the length scale of a few covalent bonds (Å) but require large energy inputs and strains on the micro-to-macro scale in order to achieve even low levels of mechanophore activation. The minimal activation hinders the translation of the available chemical responses into materials and device applications. The mechanophore activation challenge inspires core questions at yet another length scale of chemical control, namely: What are the molecular-scale features of a polymeric material that determine the extent of mechanophore activation? Further, how do we marry advances in the chemistry of polymer networks with the chemistry of mechanophores to create stress-responsive materials that are well suited for an intended application? In this Perspective, we speculate as to the potential match between covalent polymer mechanochemistry and recent advances in polymer network chemistry, specifically, topologically controlled networks and the hierarchical material responses enabled by multi-network architectures and mechanically interlocked polymers. Both fundamental and applied opportunities unique to the union of these two fields are discussed.