Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Nature, Published online: 17 March 2021; doi:10.1038/s41586-021-03215-w
An artificial intelligence system that can engage in a competitive debate with humans is presented.
Nature, Published online: 03 February 2021; doi:10.1038/s41586-021-03213-y
Bayesian optimization is applied in chemical synthesis towards the optimization of various organic reactions and is found to outperform scientists in both average optimization efficiency and consistency.Nature, Published online: 27 January 2021; doi:10.1038/d41586-021-00187-9
Regulators will soon grapple with how to safely administer powerful psychedelics for treating depression and post-traumatic stress disorder.
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.
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.
Cs2CO3 reaction system enables stereospecific reaction of functionalized tertiary alkyl bromides and bulky alcohols. The reaction occurred with retention of configuration.
Nucleophilic substitutions, including SN1 and SN2, are classical and reliable reactions, but a serious drawback is their intolerance for both bulky nucleophiles and chiral tertiary alkyl electrophiles for the synthesis of a chiral quaternary carbon center. An SRN1 reaction via a radical species is another conventional method used to carry out substitution reactions of bulky nucleophiles and alkyl halides, but chiral tertiary alkyl electrophiles cannot be used. Therefore, a stereospecific nucleophilic substitution reaction using chiral tertiary alkyl electrophiles and bulky nucleophiles has not yet been well studied. In this paper, we describe the reaction of tertiary alkyl alcohols and non‐chiral or chiral α‐bromocarboxamides as a tertiary alkyl source for the formation of congested ether compounds possessing two different tertiary alkyl groups on the oxygen atom with stereoretention.
In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/vis, IR and UHPLC) in the multistep synthesis of an active pharmaceutical ingredient, mesalazine. This synthetic route exploits flow processing for nitration, high temperature hydrolysis and hydrogenation reactions, as well as three inline separations. Advanced data analysis models were developed (indirect hard modelling, deep learning and partial least squares regression), to quantify the desired products, intermediates and impurities in real time, at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating both steady state and dynamic experiments and represents a significant step forward in data‐driven continuous flow synthesis.
Wrapping with ribbons: Chiral bis(urea) amphiphiles can translate their molecular scale chiral information to the mesoscopic level via self‐assembly in water. The morphology of the aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons. The system presents thermo‐responsive aggregation properties, in which a ribbon‐to‐vesicles transition occurs upon heating.
We present the synthesis and self‐assembly of a chiral bis(urea) amphiphile and show that chirality offers a remarkable level of control towards different morphologies. Upon self‐assembly in water, the molecular‐scale chiral information is translated to the mesoscopic level. Both enantiomers of the amphiphile self‐assemble into chiral twisted ribbons with opposite handedness, as supported by Cryo‐TEM and circular dichroism (CD) measurements. The system presents thermo‐responsive aggregation behavior and combined transmittance measurements, temperature‐dependent UV, CD, TEM, and micro‐differential scanning calorimetry (DSC) show that a ribbon‐to‐vesicles transition occurs upon heating. Remarkably, chirality allows easy control of morphology as the self‐assembly into distinct aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons.
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.
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.
Open Access  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Research suggests that borate could have mediated the prebiotic synthesis of RNA precursors (ribose, ribonucleosides, and ribonucleotides) in reactions relevant for the origin of life. This minireview provides an overview of recent developments in prebiological chemistry related to boron species.
Boron(III), as borate (or boric acid), mediates the synthesis of ribose, ribonucleosides, and ribonucleotides. These reactions are carried out under moderate temperatures (typically 70–95 °C) with organic molecules (or their derivatives) detected in interstellar space and inorganic ions found in minerals on Earth (and could occur during early stages of prebiotic evolution). Research in this century suggests that borate was a relevant prebiological reagent, thus reinforcing the RNA world hypothesis as an explanation for the origin of life. Herein, these developments on prebiological chemistry related to boron species are reviewed.
Personalized properties: Mono‐, di‐, and trifluorinated glucopyranose analogues have been synthesized. The analogues with a fluorine atom at C‐6 were usually found to be the most hydrophilic, those with vicinal polyfluorinated motifs were the most lipophilic. Solvation energies were also computed. These results should help to develop novel personalized fluoroglycoconjugates with optimal pharmacokinetics properties.
In this work, we synthesized all mono‐, di‐, and trifluorinated glucopyranose analogues at positions C‐2, C‐3, C‐4, and C‐6. This systematic investigation allowed us to perform direct comparison of 19F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C‐6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web‐based programs.
Double disruption: Esterase mediated cleavage of a protransporter leads to the formation of synthetic ion channel in bilayer membrane. Activation of the ion channel inside cells leads to ion transport across the plasma membrane, which causes apoptosis through the mitochondrial pathway and disrupts autophagy by dissipating the pH gradient of the lysosomes in cancer cells.
The formation of a supramolecular synthetic M+/Cl− channel in the membrane phospholipid bilayer has been reported upon activation of a methyl pivalate‐linked N 1,N 3‐dialkyl‐2‐hydroxyisophthalamide by esterases. The channel formation induces apoptosis in cancer cells via the intrinsic pathway. Interestingly, the supramolecular channel was also shown to disrupt autophagy in cancer cells by causing alkalization of lysosomes – a feature that has been confirmed at the cellular and protein level.
The challenge of prebiotic chemistry is to trace the syntheses of life’s key building blocks from a handful of primordial substrates. Here we report a forward-synthesis algorithm that generates a full network of prebiotic chemical reactions accessible from these substrates under generally accepted conditions. This network contains both reported and previously unidentified routes to biotic targets, as well as plausible syntheses of abiotic molecules. It also exhibits three forms of nontrivial chemical emergence, as the molecules within the network can act as catalysts of downstream reaction types; form functional chemical systems, including self-regenerating cycles; and produce surfactants relevant to primitive forms of biological compartmentalization. To support these claims, computer-predicted, prebiotic syntheses of several biotic molecules as well as a multistep, self-regenerative cycle of iminodiacetic acid were validated by experiment.
Adsorption involves molecules colliding at the surface of a solid and losing their incidence energy by traversing a dynamical pathway to equilibrium. The interactions responsible for energy loss generally include both chemical bond formation (chemisorption) and nonbonding interactions (physisorption). In this work, we present experiments that revealed a quantitative energy landscape and the microscopic pathways underlying a molecule’s equilibration with a surface in a prototypical system: CO adsorption on Au(111). Although the minimum energy state was physisorbed, initial capture of the gas-phase molecule, dosed with an energetic molecular beam, was into a metastable chemisorption state. Subsequent thermal decay of the chemisorbed state led molecules to the physisorption minimum. We found, through detailed balance, that thermal adsorption into both binding states was important at all temperatures.
Wrapping with ribbons: Chiral bis(urea) amphiphiles can translate their molecular scale chiral information to the mesoscopic level via self‐assembly in water. The morphology of the aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons. The system presents thermo‐responsive aggregation properties, in which a ribbon‐to‐vesicles transition occurs upon heating.
We present the synthesis and self‐assembly of a chiral bis(urea) amphiphile and show that chirality offers a remarkable level of control towards different morphologies. Upon self‐assembly in water, the molecular‐scale chiral information is translated to the mesoscopic level. Both enantiomers of the amphiphile self‐assemble into chiral twisted ribbons with opposite handedness, as supported by Cryo‐TEM and circular dichroism (CD) measurements. The system presents thermo‐responsive aggregation behavior and combined transmittance measurements, temperature‐dependent UV, CD, TEM, and micro‐differential scanning calorimetry (DSC) show that a ribbon‐to‐vesicles transition occurs upon heating. Remarkably, chirality allows easy control of morphology as the self‐assembly into distinct aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons.
The dynamic covalent self‐assembly of 14 units of bis(perfluorocatecholato)silane leads to [Si(O 2 C 6 F 4 )2] 14 – the first giant perfluorinated macrocycle. The oligomerization process is monitored spectroscopically, and the consummate macrocycle analyzed by single‐crystal x‐ray diffraction. The molecule spans a rigid cavity that can host two o ‐closo‐dodecacarboranes. Computations rationalize the consistent and reproducible formation of the 14mer and disclose a non‐catalyzed Si‐O/Si‐O σ‐bond metathesis with an exceptionally low energetic barrier. For the first time, the most prevalent linker in our geosphere–SiO 4 –is disposed to construct a shape‐defined crystalline macromolecule.
Supramolecular polymers formed from phosphodiester‐bridged phenanthrene trimers are doped with charged and uncharged acceptor chromophores. Excitation of the phenanthrenes is followed by efficient energy transfer to the acceptor molecules.
A supramolecular light‐harvesting antenna consisting of 3,6‐disubstituted phosphodiester‐linked phenanthrene trimers (donors) was doped with different charged and uncharged polyaromatic and heteroaromatic acceptor chromophores. Excitation of the phenanthrene moieties is followed by energy transfer to the acceptor molecules and radiative relaxation. The self‐assembled fiber structure of the phenanthrene trimers is not altered by the dopant, as verified by atomic force microscopy (AFM). Among several neutral and cationic acceptor chromophores, benzo(a)pyrene emerged as one of the highest fluorescence quantum yields, reaching 31 % at a chromophore/phenanthrene ratio of 12 mol‐%. The energy transfer is probably a combination of Förster resonance energy transfer (FRET) and a coherent energy transfer mechanism.
