The paper analyses the justification of personal integrity in ethical theories in contemporary moral epistemology. In the first chapter we present a theological consideration of the fundamental ...option that illustrates the complexity of agency of moral knowledge in the epistemic evaluation of a moral act as a specifically human conduct. Then, in the second chapter we briefly describe the inference and the structure of moral knowledge in ethical theories. In the last chapter, we argue why our personal integrity, our own understanding of it in self-estimation is related to the possibility of moral knowledge. We claim that moral knowledge is crucial in development of moral integrity of a person. The speculations on the possibility of their inference and cognitive capacity reflect on the epistemic disposition of the human being as a moral agent. Although ethical theories have offered a scientifically and methodologically precise frame to justify the truthfulness of moral knowledge and judgments, they have not anticipated the important fact of integrity between the intention, free will and practical reason.
Predmet rasprave u ovom članku je vezan za problem osobnog integriteta u etičkim teorijama u suvremenoj moralnoj epistemologiji. U prvom dijelu smo predstavili teološko razmatranje temeljenog opredjeljenja koje ilustrira složenost djelovanja moralne spoznaje za epistemičko vrednovanje moralnog čina kao specifičnog ljudskog čina. Stoga smo u drugom opisali u kratkim crtama izvođenje i strukturu moralne spoznaje u etičkim teorijama. U zadnjem dijelu, pokušali smo opravdati postavku o povezanosti opravdanja našeg osobnog integriteta, našeg razumijevanja vlastite pravednosti s etičkim spekulacijama o vjerojatnosti moralne spoznaje.
With COVID-19 surging across the world, understanding the effectiveness of intervention strategies on transmission dynamics is of primary global health importance. Here, we develop and analyze an ...epidemiological compartmental model using multi-objective genetic algorithm design optimization to compare scenarios related to strategy type, the extent of social distancing, time window, and personal protection levels on the transmission dynamics of COVID-19 in São Paulo, Brazil. The results indicate that the optimal strategy for São Paulo is to reduce social distancing over time with a stepping-down reduction in the magnitude of social distancing every 80-days. Our results also indicate that the ability to reduce social distancing depends on a 5-10% increase in the current percentage of people strictly following protective guidelines, highlighting the importance of protective behavior in controlling the pandemic. Our framework can be extended to model transmission dynamics for other countries, regions, states, cities, and organizations.
The stereochemical outcome of most aminocatalytic transformations is determined by the steric‐shielding or hydrogen‐directing approach. However, in recent years several reactions have appeared in ...which the stereochemical outcome is beyond these two approaches. This Concept article will highlight such reactions and postulate that the stereochemical outcome can be accounted for by electrostatic interactions between the catalyst‐bound substrate and the reagent in the transition state.
The law of attraction: What determines the stereochemical outcome in aminocatalytic transformations when the steric‐shielding or hydrogen‐directing approach is not possible? The Concept article will postulate that the stereochemical outcome can be accounted for by electrostatic interactions between the catalytic bound substrate and the reagent in the transition state.
A novel asymmetric organocatalytic 1,6‐addition/1,4‐addition sequence to 2,4‐dienals is described. Based on a 1,6‐Friedel–Crafts/1,4‐oxa‐Michael cascade, the organocatalyst directs the reaction of ...hydroxyarenes with a vinylogous iminium‐ion intermediate to give only one out of four possible regioisomers, thus providing optically active chromans in high yields and 94–99 % ee. Furthermore, several transformations are presented, including the formation of an optically active macrocyclic lactam. Finally, the mechanism for the novel reaction is discussed based on computational studies.
One six one four: Based on a 1,6‐Friedel–Crafts/1,4‐oxa‐Michael sequence, an organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium‐ion intermediate to give only one out of four possible regioisomers. The reaction provides optically active chromans in high yields with up to 99 % ee.
Interfacial or separate phase location of carbonaceous nanofillers (graphene and carbon nanotubes) in polymer blends with co‐continuous phases can lead to double percolation behavior, significantly ...increasing rheological and electrical properties. The prediction of the morphology and the location of the nanofillers has been used as a tool to evaluate the proprieties of co‐continuous polymer blends. This work aims to highlight the superior conductivity levels achieved using a low amount of carbon‐based fillers, by the proper selection in a multiphase polymer matrix as a template for controlled dispersion and spatial distribution of the nanoparticles, offering a compromise between easy processability and enhanced performance. Here, two polymers (linear low‐density polyethylene LLDPE and ethylene‐co‐methylacrylate EMA) and their co‐continuous blend (LLDPE/EMA) were loaded with nanofillers (few‐layer graphene FLG, few‐walled carbon nanotube FWCNT) via continuous melt mixing in twin‐screw extrusion, separate and simultaneously. It was observed that the addition of the nanofillers changed the co‐continuity of the blend, with the probable migration of the nanofillers from the EMA (hydrophilic) phase to the LLDPE (hydrophobic) phase. Rheological percolation occurred preferentially in blends containing FWCNT and FLG/FWCNT. Electrical conductivity was observed in all compositions, with higher electrical conductivity being noticed in hybrids.
Co‐continuous blend morphology of linear low‐density polyethylene/poly(ethylene‐co‐methyl acrylate) was designed and subsequently confirmed. Rheological percolation occurred preferentially in blends containing few‐walled carbon nanotube (FWCNT) and few‐layer graphene/FWCNT. Electrical conductivity between 10−5 and 10−4 S/cm was achieved, without surfactant.
Association of the initiation factor eIF4E with the mRNA cap structure is a key step for translation. Trypanosomatids present six eIF4E homologues, showing a low conservation and also differing ...significantly from the IF4Es of multicellular eukaryotes. On the mRNA side, while in most eukaryotes the mRNA contains cap-0 (7-methyl-GTP), the trypanosomatid mRNA features a cap-4, which is formed by a cap-0, followed by the AACU sequence containing 2'-O-ribose methylations and base methylations on nucleotides 1 and 4. The studies on eIF4E-cap-4 interaction have been hindered by the difficulty to synthesize this rather elaborated cap-4 sequence. To overcome this problem, we applied a liquid-phase oligonucleotide synthesis strategy and describe for the first time the crystal structure of a trypanosomatid eIF4E (T. cruzi EIF4E5) in complex with cap-4. The TcEIF4E5-cap-4 structure allowed a detailed description of the binding mechanism, revealing the interaction mode for the AACU sequence, with the bases packed in a parallel stacking conformation and involved, together with the methyl groups, in hydrophobic contacts with the protein. This binding mechanism evidences a distinct cap interaction mode in comparison with previously described eIF4E structures and may account for the difference of TcEIF4E5-cap-4 dissociation constant in comparison with other eIF4E homologues.
Flavonoids and cannabinoids comprise two large families of natural products that contain a chromane moiety in their structure. Their therapeutic potential has been extensively investigated as ...potential treatments to several diseases, ranging from cancer to infectious and neurodegenerative diseases. Despite their relative structural simplicity, in recent years creative synthetic methodologies were designed to overcome limitations from the previous synthetic strategies applied to these compounds. The aim of this review is to provide a comprehensive overview of all the enantioselective organocatalytic strategies that have been applied to the synthesis of flavonoids and cannabinoids to date.
The front cover picture, made by the graphic designer Isabela Guzman (São Paulo ‐ Brazil) and used with permission, illustrates a Δ9‐tetrahydrocannabinol (THC) molecule surrounded by a pair of hands ...and by leaves from Cannabis sativa, the plant from which THC originates. The hands are a metaphor for the presence of chirality in this class of compounds, given that they are typically isolated as single enantiomers. Details can be found in the Review by Andreu Vidal‐Albalat and Bruno Matos Paz (A. Vidal‐Albalat, B. M. Paz, Adv. Synth. Catal. 2024, 366, 1032–1043; DOI: 10.1002/adsc.202301168)
Asymmetric organocatalysis has witnessed a remarkable development since its “re-birth” in the beginning of the millenium. In this rapidly growing field, computational investigations have proven to be ...an important contribution for the elucidation of mechanisms and rationalizations of the stereochemical outcomes of many of the reaction concepts developed. The improved understanding of mechanistic details has facilitated the further advancement of the field. The diarylprolinol-silyl ethers have since their introduction been one of the most applied catalysts in asymmetric aminocatalysis due to their robustness and generality. Although aminocatalytic methods at first glance appear to follow relatively simple mechanistic principles, more comprehensive computational studies have shown that this notion in some cases is deceiving and that more complex pathways might be operating. In this Account, the application of density functional theory (DFT) and other computational methods on systems catalyzed by the diarylprolinol-silyl ethers is described. It will be illustrated how computational investigations have shed light on the structure and reactivity of important intermediates in aminocatalysis, such as enamines and iminium ions formed from aldehydes and α,β-unsaturated aldehydes, respectively. Enamine and iminium ion catalysis can be classified as HOMO-raising and LUMO-lowering activation modes. In these systems, the exclusive reactivity through one of the possible intermediates is often a requisite for achieving high stereoselectivity; therefore, the appreciation of subtle energy differences has been vital for the efficient development of new stereoselective reactions. The diarylprolinol-silyl ethers have also allowed for novel activation modes for unsaturated aldehydes, which have opened up avenues for the development of new remote functionalization reactions of poly-unsaturated carbonyl compounds via di-, tri-, and tetraenamine intermediates and vinylogous iminium ions. Computational studies have played a pivotal role in the elucidation of the regioselectivities observed for such systems because these pose a challenge due to the presence of multiple reactive sites in these intermediates. Charge distribution and π-orbital coefficient calculations have been applied to explain the observed regioselectivity of the given reactions. The calculation of more elaborate energetic pathways has allowed for in silico identification of high-energy intermediates, such as zwitterions, and transition-state structures, which have also provided information on the driving force controlling the reaction course and outcome.
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