This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins ...and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.
Partant d’une comparaison contrastive entre la formation des décisions collégiales de la Cour suprême des États-Unis (SCOTUS) et du Tribunal fédéral suprême brésilien (STF), fondées sur le principe ...de majorité, ce travail met en perspective l’affirmation, commune dans le champ juridique au Brésil, selon laquelle le STF aurait été forgé à l’image de la Cour suprême nord-américaine, en opérant ainsi un rapprochement entre les deux systèmes.
A partir da comparação por contraste entre a formação das decisões colegiadas da Suprema Corte dos Estados Unidos da América (SCOTUS) e do Supremo Tribunal Federal Brasileiro (STF), orientadas pelo princípio da maioria, o presente trabalho problematiza a afirmação, corrente no campo jurídico brasileiro, de que o STF teria sido forjado à imagem e semelhança da Suprema Corte Norte-Americana, aproximando-se assim os dois sistemas.
Starting with a contrastive comparison between the formation of collegial decisions by the Supreme Court of the United States (SCOTUS) and the Brazilian Supreme Federal Court (STF), based on the majority principle, this paper puts into perspective the assertion, common in the Brazilian legal field, that the STF was forged in the image of the North American Supreme Court, thus bringing the two systems closer together.
The media and even the specialized literature report that the ultraviolet (UV) protection for sunglasses is critical, on the grounds that sunglasses can have a counter effect if the lenses do not ...provide adequate UV protection. They reason that the primary and natural mechanism is that the pupil of the eye contracts to attenuate radiation and protect the inner eye under sun exposure. Therefore, if dark lenses do not provide appropriate UV protection, there is an increased UV incidence in the inner eye due to pupil dilation, which enhances the adverse effects and impacts the ocular tissues more severely than in situations without UV protection. However, no existing literature properly quantified or supported this argument. In this work, the influx of solar UV throughout the pupil of the eye was calculated in two situations: when a person wear sunglasses and when he/she does not. In both situations, the pupil dilation and the field of view (squint) were considered with their dependence on the brightness of the ambient, calculated by modeling the solar irradiation. Finally, it was assessed whether sunglasses with poor UV protection actually increase the UV influx throughout the dilated pupil compared to the non-dilated pupil. A set of 214 sunglasses lenses were tested and the results show that pupil dilation does not play an important role in the UV influx throughout the pupil. It was observed that the FOV is the main player, surpassing the pupil size contribution by up to 314.3%, disproving the common explanation. Because of the major role of the FOV, our results show that sunglasses with UV-A protection below 86% may have a slight potential to increase hazards to the eye compared to not wearing sunglasses at all. These results can have direct impact on sunglasses standards regarding the UV protection linked to the category of the lenses.
The construction of diverse sp3‐rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of ...2,7‐diazabicyclo3.2.1octanes (bridged 1,3‐diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4‐substituted quinoline substrates, with subsequent Hantzsch ester‐promoted reduction to a dihydropyridine intermediate which undergoes in situ two‐electron ring closure to form the bridged diazepane architecture. A wide scope of N‐arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all‐carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.
Building bridges: The reductive photocatalytic dearomatization of quinoline derivatives using N‐arylimines is described. The bridged 1,3‐diazepane architecture is constructed through the addition of an intermediary α‐amino radical to the C4‐position of a 4‐substituted quinoline and subsequent reductive cyclization.
We describe the first theoretical study of a landmark example of chiral anion phase-transfer catalysis: the enantioselective ring-opening of meso-aziridinium and episulfonium cations promoted by ...asymmetric counteranion-directed catalysis (ACDC). The mechanism of ion-pairing, ring-opening, and catalyst deactivation have been studied in the condensed phase with both classical and quantum methods using explicitly and implicitly solvated models. We find that the stability of chiral ion-pairs, a prerequisite for asymmetric catalysis, is dominated by electrostatic interactions at long range and by CH···O interactions at short range. The decisive role of solvent upon ion-pair formation and of nonbonding interactions upon enantioselectivity are quantified by complementary computational approaches. The major enantiomer is favored by a smaller distortion of the substrate, demonstrated by a distortion/interaction analysis. Our computational results rationalize the stereoselectivity for several experimental results and demonstrate a combined classical/quantum approach to perform realistic modeling of chiral counterion catalysis in solution.
Calculating reaction energy profiles to aid in mechanistic elucidation has long been the domain of the expert computational chemist. Here, we introduce autodE (https://github.com/duartegroup/autodE), ...an open‐source Python package capable of locating transition states (TSs) and minima and delivering a full reaction energy profile from 1D or 2D chemical representations. autodE is broadly applicable to study organic and organometallic reaction classes, including addition, substitution, elimination, migratory insertion, oxidative addition, and reductive elimination; it accounts for conformational sampling of both minima and TSs and is compatible with many electronic structure packages. The general applicability of autodE is demonstrated in complex multi‐step reactions, including cobalt‐ and rhodium‐catalyzed hydroformylation and an Ireland–Claisen rearrangement.
The program package autodE transforms mechanistic hypotheses from 2D chemical sketches to conformationally sampled 3D geometries using current computational best practices. Amongst other functions, autodE can generate full reaction profiles for complex reactions in a fully automated way.
Self-assembled cages have emerged as novel platforms to explore bioinspired catalysis. While many different size and shape supramolecular structures are now readily accessible, only a few are known ...to accelerate chemical reactions under substoichiometric conditions. These limited examples point to a poor understanding of cage catalysis in general, limiting the ability to design new systems. Here we show that a simple and efficient density-functional-theory-based methodology, informed by explicitly solvated molecular dynamics and coupled cluster calculations, is sufficient to accurately reproduce experimental guest binding affinities (MAD = 1.9 kcal mol–1) and identify the catalytic Diels–Alder proficiencies (>80% accuracy) of two homologous Pd2L4 metallocages with a variety of substrates. This analysis reveals how subtle structural differences in the cage framework affect binding and catalysis. These effects manifest in a smaller distortion and more favorable interaction energy for the catalytic cage compared to the inactive structure. This study gives detailed insight that would otherwise be difficult to obtain from experiments, providing new opportunities in the design of catalytically active supramolecular cages.
Metallocages offer a diverse and underexplored region of chemical space in which to search for novel catalysts and substrate hosts. However, the ability to tailor such structures toward applications ...in binding and catalysis is a challenging task. Here, we present an open-source computational toolkit, cgbind, that facilitates the construction, characterization, and prediction of functional metallocages. It employs known structural scaffolds as starting points and computationally efficient approaches for property evaluation. We demonstrate the ability of cgbind to construct libraries of cages with varied topologies and linker functionalities, generate accurate geometries (RMSD < 1.5 Å to crystal structures), and predict substrate binding with accuracy on par with semiempirical QM, all in seconds. The cgbind code presented here is freely available at github.com/duartegroup/cgbind and also via a web-based graphical user interface at cgbind.chem.ox.ac.uk. The protocol described here paves the way for high-throughput virtual screening of potential supramolecular structures, accelerating the search for new hosts and catalysts.
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