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The accuracy of the training data limits the accuracy of bulk properties from machine-learned potentials. For example, hybrid functionals or wave-function-based quantum chemical methods are readily available for cluster data but effectively out of scope for periodic structures. We show that local, atom-centered descriptors for machine-learned potentials enable the prediction of bulk properties from cluster model training data, agreeing reasonably well with predictions from bulk training data. We demonstrate such transferability by studying structural and dynamical properties of bulk liquid water with density functional theory and have found an excellent agreement with experimental and theoretical counterparts. [ABSTRACT FROM AUTHOR]

Pyrazolones represent an important structural motif in active pharmaceutical ingredients. Their asymmetric synthesis is thus widely studied. Still, a generally highly enantio‐ and diastereoselective 1,4‐addition to nitroolefins providing products with adjacent stereocenters is elusive. In this article, a new polyfunctional CuII‐1,2,3‐triazolium‐aryloxide catalyst is presented which enables this reaction type with high stereocontrol. DFT studies revealed that the triazolium stabilizes the transition state by hydrogen bonding between C(5)−H and the nitroolefin and verify a cooperative mode of activation. Moreover, they show that the catalyst adopts a rigid chiral cage/pore structure by intramolecular hydrogen bonding, by which stereocontrol is achieved. Control catalyst systems confirm the crucial role of the triazolium, aryloxide and CuII, requiring a sophisticated structural orchestration for high efficiency. The addition products were used to form pyrazolidinones by chemoselective C=N reduction. These heterocycles are shown to be valuable precursors toward β,γ'‐diaminoamides by chemoselective nitro and N−N bond reductions. Morphological profiling using the Cell painting assay identified biological activities for the pyrazolidinones and suggest modulation of DNA synthesis as a potential mode of action. One product showed biological similarity to Camptothecin, a lead structure for cancer therapy. [ABSTRACT FROM AUTHOR]

For decades there were many attempts to dispense with stoichiometric amounts of metal reagents for the synthesis of secondary alcohols. In 2021, the synthetic results of Newman and collaborators pioneered a synthesis still with metals, but not as reactants. Instead, they serverd as catalytic engines. Here we present a description by means of Density Functional Theory calculations of how this process can occur, and an attempt is made to shed light on the mechanism that facilitates the attainment of secondary alcohols, emphasizing the eternal cross‐coupling debate of whether the catalytically active species is Ni(0) or they are really taking shortcuts following the course of Ni(II). Effective Orbital analyses give a clear picture. Furthermore, this paper provides insight not only into the nature of the ligands of the metal catalyst but also the role of the base. [ABSTRACT FROM AUTHOR]

Amines are a ubiquitous class of compounds found in a variety of functional organic building blocks. Within the past years, hydrogen autotransfer catalysis has evolved as a new concept for the synthesis of amines. A through understanding of the mechanism of these reactions is necessary to design optimal catalysts. We investigate secondary amine formation catalyzed by a NNNN(P)Ru‐complex and provide understanding on the three reaction steps involved. We find that the ligand has to open one coordination site in order to allow the formation of a metal hydride intermediate. In a second step, a condensation reaction, which could also happen uncatalyzed in solution, is significantly enhanced by the presence of the ruthenium complex. The back‐transfer of the hydride to the substrate in a third step regenerates the catalyst. [ABSTRACT FROM AUTHOR]

A trivial flaw in the utilization of artificial neural networks in interpolating chemical potential energy surfaces (PES) whose descriptors are Cartesian coordinates is their dependence on simple translations and rotations of the molecule under consideration. A different set of descriptors can be chosen to circumvent this problem, internuclear distances, inverse internuclear distances or z‐matrix coordinates are three such descriptors. The objective is to use an interpolated PES in instanton rate constant calculations, hence information on the energy, gradient, and Hessian is required at coordinates in the vicinity of the tunneling path. Instanton theory relies on smoothly fitted Hessians, therefore we use energy, gradients, and Hessians in the training procedure. A major challenge is presented in the proper back‐transformation of the output gradients and Hessians from internal coordinates to Cartesian coordinates. We perform comparisons between our method, a previous approach and on‐the‐fly rate constant calcuations on the hydrogen abstraction from methanol and on the hydrogen addition to isocyanic acid. © 2018Wiley Periodicals, Inc. The challenge of utilizing instanton theory on interpolated potential energy surfaces, trained using a deep neural network, where energies, gradients and Hessians are required, in coordinates invariant to rotational and translational degrees of freedom, has been examined in this contribution. One of the studied reactions, shows good agreement both with existing neural network based approaches and with on‐the‐fly rate calculations based on a UCCSD(T)‐pVTZ‐F12 potential energy surface. [ABSTRACT FROM AUTHOR]

Formylglycine generating enzyme is a copper and oxygen-dependent protein, which catalyzes C-H activation, namely the transformation of peptidyl cysteine to formylglycine. No crystal structures of the enzyme containing copper were published so far. Here, we show by combinations of density functional theory with force fields in the QM/MM approach how copper can be incorporated in the enzyme based on two crystal structures containing Ag(I) and Cd(II) in place of Cu(I) and Cu(II). While we find a linear coordination for Cu(I) and a distorted octahedral environment for Cu(II) we also find the possibility of tetrahedral coordinations in both cases. This structural flexibility may allow the enzyme to catalyze the redox process and accommodate copper in both oxidation states. [ABSTRACT FROM AUTHOR]

Lewis pair polymerization employing N-Heterocyclic olefins (NHOs) and simple metal halides as co-catalysts has emerged as a useful tool to polymerize diverse lactones. To elucidate some of the mechanistic aspects that remain unclear to date and to better understand the impact of the metal species, computational methods have been applied. Several key aspects have been considered: (1) the formation of NHO-metal halide adducts has been evaluated for eight different NHOs and three different Lewis acids, (2) the coordination of four lactones to MgCl2 was studied and (3) the deprotonation of an initiator (butanol) was investigated in the presence and absence of metal halide for one specific Lewis pair. It was found that the propensity for adduct formation can be influenced, perhaps even designed, by varying both organic and metallic components. Apart from the NHO backbone, the substituents on the exocyclic, olefinic carbon have emerged as interesting tuning site. The tendency to form adducts is ZnCl2 > MgCl2 > LiCl. If lactones coordinate to MgCl2, the most likely binding mode is via the carbonyl oxygen. A chelating coordination cannot be ruled out and seems to gain importance upon increasing ring-size of the lactone. For a representative NHO, it is demonstrated that in a metal-free setting an initiating alcohol cannot be deprotonated, while in the presence of MgCl2 the same process is exothermic with a low barrier. [ABSTRACT FROM AUTHOR]

Nitrogenase converts gaseous dinitrogen into biologically accessible ammonia. The binding of N2 to a reduced and protonated form of the FeMo-cofactor of nitrogenase including its central carbon ligand was investigated by means of density functional calculations. It was found the central ligand to stabilize the cluster. N2 can associate to iron or molybdenum with iron being the preferred binding site. While endo and exo binding modes were investigated the exo modes are more stable. Implications on the mechanism of N2 reduction are discussed. [ABSTRACT FROM AUTHOR]