Computational chemistry articles within Nature Chemistry

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  • Article
    | Open Access

    Atomistic simulations have a broad range of applications from drug design to materials discovery. Machine learning interatomic potentials (MLIPs) have become an efficient alternative to computationally expensive ab initio simulations. Now a general reactive MLIP (called ANI-1xnr) has been developed and validated against a broad range of condensed-phase reactive systems.

    • Shuhao Zhang
    • , Małgorzata Z. Makoś
    •  & Justin S. Smith

  • Article |

    Dual-pharmacophore DNA-encoded chemical libraries enable the identification of two synergistic binders for a biological target, but subsequent linking of this pair is required to obtain a full ligand, which can be challenging. Here we report a protein-templated selection of DNA-encoded dynamic library that can identify full ligands from fragment libraries without the need for subsequent fragment linking.

    • Yu Zhou
    • , Wenyin Shen
    •  & Xiaoyu Li

  • News & Views |

    Open-shell organic molecules with properties that can be modulated by external stimuli are of interest for spintronics applications. Now, an overcrowded alkene with open-shell tetraradical character has been synthesized in which the interaction between the π-conjugated subunits depends on the charge and spin state.

    • Yoshito Tobe

  • Article
    | Open Access

    Tetrafluorenofulvalene (TFF) defies conventional rules of bond strength in organic chemistry. In particular, the central alkene bond of TFF becomes stronger in the quintet state and in the tetraanion. These changes arise from the unusual interplay between the twist, aromaticity and spin pairing in the π-electron system of TFF.

    • Bibek Prajapati
    • , Madan D. Ambhore
    •  & Marcin Stępień

  • Article |

    Contrary to agonist binding being the sole driver for β2-adrenergic receptor (β2AR) activation, molecular metadynamics simulations now reveal a distinct activation mechanism. Coupling β2AR with its cognate Gs protein induces considerable structural changes, activating both proteins. Gs opens its GDP binding pocket while β2AR undergoes expansion.

    • Amirhossein Mafi
    • , Soo-Kyung Kim
    •  & William A. Goddard III

  • Article |

    Clathrates—open crystals with a hierarchy of polyhedral cages—are mostly found in atomic and molecular systems. Now, it has been shown through Monte Carlo simulations that the formation of colloidal host–guest clathrates can be driven by entropy alone, through entropy compartmentalization.

    • Sangmin Lee
    • , Thi Vo
    •  & Sharon C. Glotzer

  • Research Briefing |

    Serial rotation electron diffraction (SerialRED) enables rapid and reliable phase analysis and structure determination of complex polycrystalline materials that cannot be routinely characterized using X-ray diffraction. Five zeolite phases were identified in a single synthesis product by automated screening of hundreds of crystals, demonstrating the power of SerialRED for materials development.

  • Article
    | Open Access

    X-ray diffraction is crucial for the phase elucidation of polycrystalline materials but remains challenging for complex multiphase systems. Now serial rotation electron diffraction has been shown to enable rapid, reliable and semiquantitative phase analysis of such systems, facilitating high-throughput screening of complex synthesis systems and providing new opportunities for materials development.

    • Yi Luo
    • , Bin Wang
    •  & Xiaodong Zou

  • Article
    | Open Access

    Neutral homoaromatic hydrocarbons—which possess an interrupted π-system yet display aromatic properties owing to through-space or through-bond interactions—have remained rare as they are typically unstable. Now a class of stable neutral homoaromatic homoannulenes has been synthesized, including one that acts as a photoswitch through a reversible [1, 11] sigmatropic rearrangement.

    • Trung Tran Ngoc
    • , Niklas Grabicki
    •  & Johannes F. Teichert

  • Article |

    Enzymes with identical sequences of amino acids can display varying activities when encoded with mRNA with different properties, but why this is the case has been a mystery. Now, it has been shown that synonymous mutations in mRNA alter the partitioning of proteins into long-lived soluble misfolded states with varying activities.

    • Yang Jiang
    • , Syam Sundar Neti
    •  & Edward P. O’Brien

  • Article |

    Gold nanoparticles typically exhibit hard-sphere-like assembly behaviour, but now the size, morphology and symmetry of crystals of Au25 nanoparticles have been tuned. The presence of excess tetraethylammonium cations has been shown to promote the one-dimensional assembly of the nanoparticles, which in turn form rod-like crystals, by stabilizing dynamically detached ligands from adjacent particles into interparticle linkers through CH⋯π and ion-pairing interactions.

    • Qiaofeng Yao
    • , Lingmei Liu
    •  & Jianping Xie

  • News & Views |

    The application of machine learning to big data, to make quantitative predictions about reaction outcomes, has been fraught with failure. This is because so many chemical-reaction data are not fit for purpose, but predictions would be less error-prone if synthetic chemists changed their reaction design and reporting practices.

    • Jacqueline M. Cole

  • Article |

    The influence that liquid environments have on the ultrafast excited-state dynamics of molecules is poorly understood. Using time-resolved photoelectron spectroscopy, the dynamics of the photoisomerization of stilbene in the gas and liquid phases have now been shown to be qualitatively similar—including the observation of vibrational coherences—but the timescales are significantly longer in the liquid phase.

    • Chuncheng Wang
    • , Max D. J. Waters
    •  & Hans Jakob Wörner

  • Article |

    Amino acids are one of the major building blocks of life, but the ways in which they respond to light excitation are not fully understood. Now, the photochemistry of tyrosine has been studied using physically inspired deep neural networks, leading to the observation of unconventional dynamically controlled reactivity that involves ‘roaming’ radicals that can cause photodamage.

    • Julia Westermayr
    • , Michael Gastegger
    •  & Philipp Marquetand

  • Article |

    Catalytic transformations of methane frequently involve the formation of a metal–methane complex, but these compounds are challenging to observe. Now, a relatively long-lived osmium–methane complex has been characterized using NMR spectroscopy and forms from the direct binding of methane to a photolytically generated, coordinatively unsaturated cationic osmium–carbonyl complex dissolved in an inert hydrofluorocarbon solvent at –90 °C.

    • James. D. Watson
    • , Leslie. D. Field
    •  & Graham. E. Ball

  • Article |

    Rhodopsin activation is driven by an ultrafast double-bond isomerization, but questions remain about the origin of its sensitivity. Now, quantum–classical simulations show that, 15 fs after light absorption, a degeneracy between the reactive excited state and a neighbouring state causes the splitting of the rhodopsin population into subpopulations, which propagate with different velocities, leading to distinct contributions to the quantum efficiency.

    • Xuchun Yang
    • , Madushanka Manathunga
    •  & Massimo Olivucci

  • Article |

    Controlling the crystallographic registry of layered materials through interlayer twist angles has introduced a distinctive degree of freedom for tuning their electronic behaviour. Now, the interfacial electrochemical kinetics of solution-phase redox complexes at twisted bilayer graphene electrodes have been modulated by the angle-dependent tuning of moiré-derived flat bands.

    • Yun Yu
    • , Kaidi Zhang
    •  & D. Kwabena Bediako

  • News & Views |

    Machine learning algorithms are fast surpassing human abilities in multiple tasks, from image recognition to medical diagnostics. Now, machine learning algorithms have been shown to be capable of accurately predicting the folded structures of proteins.

    • Cecilia Clementi

  • Article |

    A haem protein that serves as a dual-function catalyst capable of inserting a carbene into a N–H bond to form α-amino lactones has been reported. The enzyme catalyses both carbene transfer and the subsequent proton transfer in a single active site. This transformation can proceed at the gram scale with high efficiency and enantioselective control.

    • Zhen Liu
    • , Carla Calvó-Tusell
    •  & Frances H. Arnold

  • Article |

    Computationally designed enzymes can be substantially improved by directed evolution. Now, it has been shown that evolution can introduce a dynamic network that selectively tightens the transition-state ensemble, giving rise to a negative activation heat capacity. Targeting such transition state conformational dynamics may expedite de novo enzyme creation.

    • H. Adrian Bunzel
    • , J. L. Ross Anderson
    •  & Adrian J. Mulholland

  • Q&A |

    Jeremy Frey, professor of physical chemistry at the University of Southampton and principal investigator for the AI3SD Network+, talks with Nature Chemistry about the perils of uncertainty in the quality of machine learning data and the synergies between AI and other technologies.

    • Russell Johnson

  • Article |

    Oxidation states help chemists to understand the bonding, properties and reactivity of compounds, but they can be difficult to determine for metal ions in extended crystalline materials. Now, oxidation states manually assigned to metal–organic frameworks have been harvested from the Cambridge Structural Database and used to build a machine-learning model that predicts oxidation states in metal–organic frameworks with good accuracy.

    • Kevin Maik Jablonka
    • , Daniele Ongari
    •  & Berend Smit

  • Comment |

    Statistical tools based on machine learning are becoming integrated into chemistry research workflows. We discuss the elements necessary to train reliable, repeatable and reproducible models, and recommend a set of guidelines for machine learning reports.

    • Nongnuch Artrith
    • , Keith T. Butler
    •  & Aron Walsh

  • Thesis |

    Michelle Francl wonders what the future will think of her office.

    • Michelle Francl

  • Article |

    Unlike ferrocene and its cationic counterpart ferrocenium, the ferrocene monoanion is an unusual species that has been observed through low-temperature electrochemical studies. Now, a family of isostructural 3d metallocenates has been isolated that consists of a manganocene, a cobaltocene and a high-spin ferrocene anion stabilized by cyclopentadienyl ligands bearing bulky aliphatic groups.

    • Conrad A. P. Goodwin
    • , Marcus J. Giansiracusa
    •  & David P. Mills

  • Article |

    High-accuracy quantum chemistry methods struggle with a combinatorial explosion of Slater determinants in larger molecular systems, but now a method has been developed that learns electronic wavefunctions with deep neural networks and reaches high accuracy with only a few determinants. The method is applicable to realistic chemical processes such as the automerization of cyclobutadiene.

    • Jan Hermann
    • , Zeno Schätzle
    •  & Frank Noé

  • Article |

    Transient metallonitrenes (M–N) have been proposed as key intermediates in nitrogen atom transfer reactions, but well-defined examples have remained elusive. Now, a platinum complex with an atomic nitrogen ligand, best described as a subvalent nitrogen diradical singly bonded to a platinum(ii) ion (Pt–N), has been isolated and shows ambiphilic reactivity.

    • Jian Sun
    • , Josh Abbenseth
    •  & Sven Schneider

  • Article |

    Scattering experiments in which two beams nearly co-propagate allow broadly tunable collision energies and can enable cold collisions. Now, such experiments have been combined with the preparation of NO molecules using stimulated emission to generate highly vibrationally excited states for state-to-state scattering studies, testing the theoretical gold standard in a regime not found in nature.

    • Chandika Amarasinghe
    • , Hongwei Li
    •  & Arthur G. Suits

  • Article |

    Compounds of main-group elements rarely undergo direct carbonylation reactions. Now, an electron-rich silylene intermediate has been shown to readily react with CO to form a silylene carbonyl complex that is stable at room temperature. This complex engages in CO substitution as well as oxidative addition reactions.

    • Chelladurai Ganesamoorthy
    • , Juliane Schoening
    •  & Stephan Schulz

  • News & Views |

    Although the application of force to induce chemical transformations is an active area of research, detailed understanding of these mechanochemical pathways is still lacking. Now, the mechanochemical activation of [4]-ladderane has been studied and found to exhibit unique non-equilibrium dynamic effects.

    • Vincenzo Lordi

  • Article |

    The mechanochemical activation of [4]-ladderane/ene has been studied and found to exhibit cascade unzipping and a consistent stereochemical distribution of products under various conditions and in different polymer backbones. Ab initio steered molecular dynamics simulations revealed unique non-equilibrium dynamic effects in the mechanochemistry of ladderane, cascade activation and reaction pathway bifurcation.

    • Zhixing Chen
    • , Xiaolei Zhu
    •  & Yan Xia

  • Article |

    The complete biosynthesis of the fungal indole alkaloid malbrancheamide, which culminates in an intramolecular [4+2] hetero-Diels–Alder cyclization to produce the bicyclo[2.2.2]diazaoctane scaffold, has now been discovered. Chemical synthesis and protein structural analysis were used to provide mechanistic insight into this enzyme-dependent diastereo- and enantioselective cycloaddition.

    • Qingyun Dan
    • , Sean A. Newmister
    •  & Robert M. Williams

  • Article |

    The structure and dynamics of hydrogen bonds in ion hydration shells are not yet fully understood, however, small ion–dihydrate molecular complexes represent ideal model systems with which to investigate the interplay between ion–water and water–water interactions. Now, state-of-the-art quantum dynamics simulations have provided evidence for tunnelling in hydrogen-bond rearrangements in the iodide–dihydrate complex.

    • Pushp Bajaj
    • , Jeremy O. Richardson
    •  & Francesco Paesani

  • Article |

    Establishing a fundamental understanding of the electronic structure of actinides remains a challenging task for both experiment and theory. Now, it is shown that for the uranium dimer, relativity and electron correlation affects not only the nature of the electronic ground state, but also lowers the bond multiplicity in comparison to previous studies.

    • Stefan Knecht
    • , Hans Jørgen Aa. Jensen
    •  & Trond Saue

  • Article |

    Inhibiting the interaction between amyloid-β (Aβ) and a neuronal cell surface receptor, LilrB2, could offer a potential route for treating Alzheimer’s disease. Now, binding sites between Aβ and LilrB2 have been discovered and computational selection has identified inhibitors that block this binding site. Cell-penetrating inhibitors were found to block the Aβ–LilrB2 interaction and limit Aβ-induced cytotoxicity.

    • Qin Cao
    • , Woo Shik Shin
    •  & Lin Jiang

  • Article |

    Binding interactions, whether between a biological receptor and ligand or between a synthetic host and guest, are frequently stronger for larger molecules than for smaller ones. This is commonly believed to arise from increased dispersion interactions, but it has now been shown that cavitation energies—always required to dissolve molecules in solution—can be more important.

    • Suhang He
    • , Frank Biedermann
    •  & Werner M. Nau

  • Article |

    Nucleophilic aromatic substitution reactions have long been thought to occur primarily via stepwise mechanisms. New and sensitive methodology for measuring carbon kinetic isotope effects now shows that most such substitutions actually occur through concerted mechanisms.

    • Eugene E. Kwan
    • , Yuwen Zeng
    •  & Eric N. Jacobsen

  • Article |

    Molecular dynamics simulations for seven members of the Src kinase family have now revealed a conserved step-wise deactivation process, potentially druggable intermediate states, and quantitatively similar thermodynamics and kinetics across the entire family.

    • Mohammad M. Sultan
    • , Gert Kiss
    •  & Vijay S. Pande

  • Article |

    Halogen bonding is known to get stronger with increasing halogen polarizability, but some trends of the periodic table break down for heavy elements owing to relativistic effects. Now, through distribution coefficient measurements and relativistic quantum mechanical calculations, AtI has been shown to form stronger halogen bonds than I2—meaning that astatine conforms to the trend.

    • Ning Guo
    • , Rémi Maurice
    •  & Nicolas Galland

  • Article |

    The rate constant of DNA hybridization varies over several orders of magnitude and is affected by temperature and DNA sequence. A machine-learning algorithm that is capable of accurately predicting hybridization rate constants has now been developed. Tests with this algorithm showed that over 90% of predictions were correct to within a factor of three.

    • Jinny X. Zhang
    • , John Z. Fang
    •  & David Yu Zhang

  • Article |

    Cross coupling under transition-metal-free conditions is an attractive and economic alternative to traditional transition-metal-catalysed methods. Metal-free coupling of azaallyls has now been demonstrated with vinyl bromide electrophiles, delivering allylic amines in excellent yields. Moreover, mechanistic evidence supports dual reaction pathways triggered by azaallyl anions and radicals.

    • Minyan Li
    • , Osvaldo Gutierrez
    •  & Patrick J. Walsh

  • Article |

    Electron-transfer-mediated decay (ETMD) is a recently discovered type of electronic relaxation that involves the refilling of a core hole by an electron from a neighbouring species. It has now been observed in LiCl solution, when previously it had only been seen in rare-gas clusters. Spectra generated during ETMD are observed to be sensitive to the immediate environment of the initially ionized ion.

    • Isaak Unger
    • , Robert Seidel
    •  & Nikolai V. Kryzhevoi

  • Perspective |

    No longer a theoretical dream, this Perspective describes effects of oriented external electric fields on rates and selectivity patterns of nonpolar reactions. Discussions of the Diels–Alder reaction, C–H and C=C bond activations and so on, underscore the potential usage of oriented electric fields as future smart catalysts, inhibitors and reagents in chemistry.

    • Sason Shaik
    • , Debasish Mandal
    •  & Rajeev Ramanan

  • News & Views |

    Density functional theory calculations can be carried out with different levels of accuracy, forming a hierarchy that is often represented by the rungs of a ladder. Now a new method has been developed that significantly improves the accuracy of the 'third rung' when calculating the properties of diversely bonded systems.

    • Roberto Car

  • Article |

    Whether a molecule or material can exist, and with what structures and energies, is of critical importance. For demanding calculations the efficiency of density functional theory makes it the only practical electronic structure theory available to help answer these questions. Now, an efficient density functional is shown to have unprecedented accuracy for a diverse set of bonded systems.

    • Jianwei Sun
    • , Richard C. Remsing
    •  & John P. Perdew

  • Article |

    L-Cysteine-derived thiazolidines have now been shown to be artificial substrates of the radical SAM enzyme HydE, which converts them into S-adenosyl-L-cysteine. Carbon–sulfur bonds are formed in a concerted mechanism that involves the formation of a C-centred radical that concomitantly attacks the S atom of a thioether. This is the first example of a radical SAM enzyme that reacts directly on a sulfur atom instead of abstracting an H-atom.

    • Roman Rohac
    • , Patricia Amara
    •  & Yvain Nicolet

  • Article |

    Avoiding equal probability for clockwise and anticlockwise rotation is essential for the function of molecular motors, and both biological and synthetic systems take advantage of chirality to control the rotary direction. Now it has been shown, by integrating two rotor moieties in a symmetric meso motor design, that light-driven unidirectional rotary motion can be achieved in an achiral system.

    • Jos C. M. Kistemaker
    • , Peter Štacko
    •  & Ben L. Feringa

  • Article |

    The question of how divalent metal ions direct the folding of ribozymes is a major unsolved problem. A computational model has now been used to reveal the molecular mechanism by which Mg2+ drives the Azoarcus ribozyme into a catalytically functional state. Simulations also show that although Ca2+ drives folding it leaves the active site unstable.

    • Natalia A. Denesyuk
    •  & D. Thirumalai

  • Article |

    Often reactions can be described by classical mechanics; however, this is prohibited in cases in which quantum phenomena emerge. Now angular distributions measured for the H + D2 reaction have been seen to display characteristic oscillation patterns in backward scattering — theory shows that they are caused by quantum interferences between classical mechanisms similar to those found in the double-slit experiment.

    • Pablo G. Jambrina
    • , Diego Herráez-Aguilar
    •  & Richard N. Zare

  • News & Views |

    Computations of the energetics and mechanism of the Morita–Baylis–Hillman reaction are “not even wrong” when compared with experiments. While computational abstinence may be the purest way to calculate challenging reaction mechanisms, taking prophylactic measures to avoid regrettable outcomes may be more realistic.

    • Arthur Winter

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