MACE: Automated Assessment of Stereochemistry of Transition Metal Complexes and Its Applications in Computational Catalysis.

Computational chemistry pipelines typically commence with geometry generation, well-established for organic compounds but presenting a considerable challenge for transition metal complexes. This paper introduces MACE, an automated computational workflow for converting chemist SMILES/MOL representations of the ligands and the metal center to 3D coordinates for all feasible stereochemical configurations for mononuclear octahedral and square planar complexes directly suitable for quantum chemical computations and implementation in high-throughput computational chemistry workflows. The workflow is validated through a structural screening of a data set of transition metal complexes extracted from the Cambridge Structural Database. To further illustrate the power and capabilities of MACE, we present the results of a model DFT study on the hemilability of pincer ligands in Ru, Fe, and Mn complexes, which highlights the utility of the workflow for both focused mechanistic studies and larger-scale high-throughput pipelines.

Switching between Hydrogenation and Olefin Transposition Catalysis via Silencing NH Cooperativity in Mn(I) Pincer Complexes.

While Mn-catalyzed (de)hydrogenation of carbonyl derivatives has been well established, the reactivity of Mn hydrides with olefins remains very rare. Herein, we report a Mn(I) pincer complex that effectively promotes site-controlled transposition of olefins. This reactivity is shown to emerge once the N-H functionality within the Mn/NH bifunctional complex is suppressed by alkylation. While detrimental for carbonyl (de)hydrogenation, such masking of the cooperative N-H functionality allows for the highly efficient conversion of a wide range of allylarenes to higher-value 1-propenybenzenes in near-quantitative yield with excellent stereoselectivities. The reactivity toward a single positional isomerization was also retained for long-chain alkenes, resulting in the highly regioselective formation of 2-alkenes, which are less thermodynamically stable compared to other possible isomerization products. The detailed mechanistic analysis of the reaction between the activated Mn catalyst and olefins points to catalysis operating via a metal-alkyl mechanism-one of the three conventional transposition mechanisms previously unknown in Mn complexes.

Basic Promotors Impact Thermodynamics and Catalyst Speciation in Homogeneous Carbonyl Hydrogenation.

Homogeneously catalyzed reactions often make use of additives and promotors that affect reactivity patterns and improve catalytic performance. While the role of reaction promotors is often discussed in view of their chemical reactivity, we demonstrate that they can be involved in catalysis indirectly. In particular, we demonstrate that promotors can adjust the thermodynamics of key transformations in homogeneous hydrogenation catalysis and enable reactions that would be unfavorable otherwise. We identified this phenomenon in a set of well-established and new Mn pincer catalysts that suffer from persistent product inhibition in ester hydrogenation. Although alkoxide base additives do not directly participate in inhibitory transformations, they can affect the equilibrium constants of these processes. Experimentally, we confirm that by varying the base promotor concentration one can control catalyst speciation and inflict substantial changes to the standard free energies of the key steps in the catalytic cycle. Despite the fact that the latter are universally assumed to be constant, we demonstrate that reaction thermodynamics and catalyst state are subject to external control. These results suggest that reaction promotors can be viewed as an integral component of the reaction medium, on its own capable of improving the catalytic performance and reshaping the seemingly rigid thermodynamic landscape of the catalytic transformation.

Property-activity relations of multifunctional reactive ensembles in cation-exchanged zeolites: a case study of methane activation on Zn2+-modified zeolite BEA.

The reactivity theories and characterization studies for metal-containing zeolites are often focused on probing the metal sites. We present a detailed computational study of the reactivity of Zn-modified BEA zeolite towards C-H bond activation of the methane molecule as a model system that highlights the importance of representing the active site as the whole reactive ensemble integrating the extra-framework ZnEF2+ cations, framework oxygens (OF2-), and the confined space of the zeolite pores. We demonstrate that for our model system the relationship between the Lewis acidity, defined by the probe molecule adsorption energy, and the activation energy for methane C-H bond cleavage performs with a determination coefficient R2 = 0.55. This suggests that the acid properties of the localized extra-framework cations can be used only for a rough assessment of the reactivity of the cations in the metal-containing zeolites. In turn, studying the relationship between the activation energy and pyrrole adsorption energy revealed a correlation, with R2 = 0.80. This observation was accounted for by the similarity between the local geometries of the pyrrole adsorption complexes and the transition states for methane C-H bond cleavage. The inclusion of a simple descriptor for zeolite local confinement allows transferability of the obtained property-activity relations to other zeolite topologies. Our results demonstrate that the representation of the metal cationic species as a synergistically cooperating active site ensembles allows reliable detection of the relationship between the acid properties and reactivity of the metal cation in zeolite materials.

From weak to strong interactions: structural and electron topology analysis of the continuum from the supramolecular chalcogen bonding to covalent bonds.

The relationship between covalent and supramolecular bonding, and the criteria of the assignments of different interactions were explored via the review of selenium and tellurium containing structures in the Cambridge Structural Database and their computational analysis using Quantum Theory of Atoms in Molecules (QTAIM). This combined study revealed continuums of the interatomic Se⋯Br and Te⋯I distances, dCh⋯X, in the series of associations from the sums of the van der Waals radii of these atoms (rCh + rX) to their covalent bond lengths. The electron densities, ρ(r), at Bond Critical Points (BCPs) along the chalcogen bond paths increased gradually from about 0.01 a.u. common for the non-covalent interactions to about 0.1 a.u. typical for the covalent bonds. The log ρ(r) values fell on the same linear trend line when plotted against normalized interatomic distances, RXY = dCh⋯X/(rCh + rX). The transition from the positive to negative values of the energy densities, H(r), at the BCPs (related to a changeover of essentially non-covalent into partially covalent interactions) were observed at RXY ≈ 0.80. Synchronous changes of bonding characteristics with RXY (similar to that found earlier in the halogen-bonded systems) designated normalized interatomic separation as a critical factor determining the nature of these bondings. The uninterrupted continuums of Te⋯I and Se⋯Br bond lengths and BCPs' characteristics signified an intrinsic link between limiting types of bonding involving chalcogen atoms and between covalent and supramolecular bonding in general.

Robust and efficient hydrogenation of carbonyl compounds catalysed by mixed donor Mn(I) pincer complexes.

Any catalyst should be efficient and stable to be implemented in practice. This requirement is particularly valid for manganese hydrogenation catalysts. While representing a more sustainable alternative to conventional noble metal-based systems, manganese hydrogenation catalysts are prone to degrade under catalytic conditions once operation temperatures are high. Herein, we report a highly efficient Mn(I)-CNP pre-catalyst which gives rise to the excellent productivity (TOF° up to 41 000 h-1) and stability (TON up to 200 000) in hydrogenation catalysis. This system enables near-quantitative hydrogenation of ketones, imines, aldehydes and formate esters at the catalyst loadings as low as 5-200 p.p.m. Our analysis points to the crucial role of the catalyst activation step for the catalytic performance and stability of the system. While conventional activation employing alkoxide bases can ultimately provide catalytically competent species under hydrogen atmosphere, activation of Mn(I) pre-catalyst with hydride donor promoters, e.g. KHBEt3, dramatically improves catalytic performance of the system and eliminates induction times associated with slow catalyst activation.

Degradation kinetic study of ZIF-8 microcrystals with and without the presence of lactic acid.

The zeolitic imidazolate framework ZIF-8 (Zn(mim)2, mim = 2-methylimidazolate) has recently been proposed as a drug delivery platform for anticancer therapy based on its capability of decomposing in acidic media. The concept presumes a targeted release of encapsulated drug molecules in the vicinity of tumor tissues that typically produce secretions with elevated acidity. Due to challenges of in vivo and in vitro examination, many studies have addressed the kinetics of ZIF-8 decomposition and subsequent drug release in phosphate buffered saline (PBS) with adjusted acidity. However, the presence of hydrogen phosphate anions [HPO4]2- in PBS may also affect the stability of ZIF-8. As yet, no separate analysis has been performed comparing the dissolving capabilities of PBS and various acidification agents used for regulating pH. Here, we provide a systematic study addressing the effects of phosphate anions with and without lactic acid on the degradation rate of ZIF-8 microcrystals. Lactic acid has been chosen as an experimental acidification agent, since it is particularly secreted by tumor cells. Interestingly, the effect of a lactic acid solution with pH 5.0 on ZIF-8 degradation is shown to be weaker compared to a PBS solution with pH 7.4. However, as an additive, lactic acid is able to enhance the decomposition efficacy of other solutions by 10 to 40 percent at the initial stage, depending on the presence of other ions. Additionally, we report mild toxicity of ZIF-8 and its decomposition products, as examined on HDF and A549 cell lines.

The accuracy challenge of the DFT-based molecular assignment of 13C MAS NMR characterization of surface intermediates in zeolite catalysis.

The influence of the model and method choice on the DFT predicted 13C NMR chemical shifts of zeolite surface methoxide species has been systematically analyzed. Twelve 13C NMR chemical shift calculation protocols on full periodic and hybrid periodic-cluster DFT calculations with varied structural relaxation procedures are examined. The primary assessment of the accuracy of the computational protocols has been carried out for the Si-O(CH3)-Al surface methoxide species in ZSM-5 zeolite with well-defined experimental NMR parameters (chemical shift, δ(13C) value) as a reference. Different configurations of these surface intermediates and their location inside the ZSM-5 pores are considered explicitly. The predicted δ value deviates by up to ±0.8 ppm from the experimental value of 59 ppm due to the varied confinement of the methoxide species at different zeolite sites (model accuracy). The choice of the exchange-correlation functional (method accuracy) introduces ±1.5 ppm uncertainty in the computed chemical shifts. The accuracy of the predicted 13C NMR chemical shifts for the computational assignment of spectral characteristics of zeolite intermediates has been further analyzed by considering the potential intermediate species formed upon methane activation by Cu/ZSM-5 zeolite. The presence of Cu species in the vicinity of surface methoxide increases the prediction uncertainty to ±2.5 ppm. The full geometry relaxation of the local environment of an active site at an appropriate level of theory is critical to ensure a good agreement between the experimental and computed NMR data. Chemical shifts (δ) calculated via full geometry relaxation of a cluster model of a relevant portion of the zeolite lattice site are in the best agreement with the experimental values. Our analysis indicates that the full geometry optimization of a cluster model at the PBE0-D3/6-311G(d,p) level of theory followed by GIAO/PBE0-D3/aug-cc-pVDZ calculations is the most suitable approach for the calculation of 13C chemical shifts of zeolite surface intermediates.

Revisiting van der Waals Radii: From Comprehensive Structural Analysis to Knowledge-Based Classification of Interatomic Contacts.

The front cover artwork is provided by the TheoMAT group of ITMO University (Russia) and the Inorganic Systems Engineering Group of Delft University of Technology (The Netherlands). The image illustrates how one can find the most probable interatomic distance and determine the van der Waals parameters for interatomic interaction from extended and diverse structural datasets. The new approach for background elimination and analysis of extended bulk structural datasets is reported in our paper. Read the full text of the Article at 10.1002/cphc.201901083.

Revisiting van der Waals Radii: From Comprehensive Structural Analysis to Knowledge-Based Classification of Interatomic Contacts.

Weak noncovalent interactions are responsible for structure and properties of almost all supramolecular systems, such as nucleic acids, enzymes, and pharmaceutical crystals. However, the analysis of their significance and structural role is not straightforward and commonly requires model studies. Herein, we describe an efficient and universal approach for the analysis of noncovalent interactions and determination of van der Waals radii using the line-of-sight (LoS) concept. The LoS allows to unambiguously identify and classify the "direct" interatomic contacts in complex molecular systems. This approach not only provides an improved theoretical base to molecular "sizes" but also enables the quantitative analysis of specificity, anisotropy, and steric effects of intermolecular interactions.

Local-structure effects on 31P NMR chemical shift tensors in solid state.

The effect of the local structure on the 31P NMR chemical shift tensor (CST) has been studied experimentally and simulated theoretically using the density functional theory gauge-independent-atomic-orbital approach. It has been shown that the dominating impact comes from a small number of noncovalent interactions between the phosphorus-containing group under question and the atoms of adjacent molecules. These interactions can be unambiguously identified using the Bader analysis of the electronic density. A robust and computationally effective approach designed to attribute a given experimental 31P CST to a certain local morphology has been elaborated. This approach can be useful in studies of surfaces, complex molecular systems, and amorphous materials.

REStLESS: automated translation of glycan sequences from residue-based notation to SMILES and atomic coordinates.

Motivation: Glycans and glycoconjugates are usually recorded in dedicated databases in residue-based notations. Only a few of them can be converted into chemical (atom-based) formats highly demanded in conformational and biochemical studies. In this work, we present a tool for translation from a residue-based glycan notation to SMILES. Results: The REStLESS algorithm for translation from the CSDB Linear notation to SMILES was developed. REStLESS stands for ResiduEs as Smiles and LinkagEs as SmartS, where SMARTS reaction expressions are used to merge pre-encoded residues into a molecule. The implementation supports virtually all structural features reported in natural carbohydrates and glycoconjugates. The translator is equipped with a mechanism for conversion of SMILES strings into optimized atomic coordinates which can be used as starting geometries for various computational tasks. Availability and implementation: REStLESS is integrated in the Carbohydrate Structure Database (CSDB) and is freely available on the web (http://csdb.glycoscience.ru/csdb2atoms.html). Supplementary information: Supplementary data are available at Bioinformatics online.

Inhibiting Low-Frequency Vibrations Explains Exceptionally High Electron Mobility in 2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ) Single Crystals.

Organic electronics requires materials with high charge mobility. Despite decades of intensive research, charge transport in high-mobility organic semiconductors has not been well understood. In this Letter, we address the physical mechanism underlying the exceptionally high band-like electron mobility in F2-TCNQ (2,5-difluoro-7,7,8,8-tetracyanoquinodimethane) single crystals among a crystal family of similar compounds Fn-TCNQ (n = 0, 2, 4) using a combined experimental and theoretical approach. While electron transfer integrals and reorganization energies did not show outstanding features for F2-TCNQ, Raman spectroscopy and solid-state DFT indicated that the frequency of the lowest vibrational mode is nearly twice higher in the F2-TCNQ crystal than in TCNQ and F4-TCNQ. This phenomenon is explained by the specific packing motif of F2-TCNQ with only one molecule per primitive cell so that electron-phonon interaction decreases and the electron mobility increases. We anticipate that our findings will encourage investigators for the search and design of organic semiconductors with one molecule per primitive cell and/or the poor low-frequency vibrational spectrum.