Influence of Steric and Dispersion Interactions on the Thermochemistry of Crowded (Fluoro)alkyl Compounds.

ConspectusAlkanes play a pivotal role in industrial, environmental, and biological processes. They are characterized by their carbon-carbon single-bond structure, remarkable stability, and conformational diversity. Fluorination of such compounds imparts unique physicochemical properties that often enhance pharmacokinetic profiles, metabolic stability, and receptor interactions while keeping beneficial properties. However, such per- and polyfluoroalkyl substances (PFAS) show a persistent presence in the environment and potential adverse health effects, which propelled them to the forefront of global environmental and health discussions. Alkyl compounds are also prototypical for stereoelectronic (SE) effects that are widely applied in chemistry. Substituents are typically described as electron-density-donating/withdrawing and/or responsible for sterically interacting with reagents or strategic groups in the molecule. That alkane branching can result in higher stability compared to less-branched isomers has been investigated in detail also by testing quantum chemical methods, in particular density functional theory (DFT). Alkane branching results in spatially compact structures with close intramolecular contacts so that at a specific size the detailed balance of attractive London dispersion and covalent versus repulsive Pauli exchange interactions shifts to new, chemically unfragile situations. This may lead to dissociation at room temperature and opens the central question: what is the smallest crowed alkane that cannot be made synthetically? In this Account, we try to shed light on the interplay among the various (free) energy components for crowded (fluoro)alkane dissociation. In this context, homolytic cleavage of the central C-C bond in a series of model alkanes of increasing size with tert-butyl (tBu), adamantyl (Ad), and [1.1.1]propellanyl (Prop) substituents is investigated. Reference energies are calculated at the PNO-LCCSD(T)-F12b level and used to benchmark the performance of contemporary DFT functionals. In line with previous conclusions, the application of dispersion corrections to density functionals is mandatory. For crowed structures, the accurate description of the midrange correlation effects, specifically repulsive van der Waals interactions, is crucial, and we observed that the density-dependent VV10 correction is superior to D4 in this context, although the asymptotic region is better described by the latter. The best available dispersion-inclusive functionals show systematic and reasonably small residual errors and can be safely applied to large systems (>100 atoms), for which coupled cluster methods with large basis sets are not computationally feasible anymore. For qualitatively correct predictions of synthetic accessibility under equilibrium conditions (free energy), the inclusion of thermostatistical (entropy) contributions is also essential. According to our results, tetra-tert-butylmethane (C17tBu) is the largest and most crowded system with a positive dissociation free energy and should be synthesizable. The difference between hydrogenated and perfluorinated systems originates from the increase in the steric repulsion of spatially close substituents, which is not compensated to the same extent by attractive orbital and dispersion interactions. A sometimes-assumed similar steric demand for fluorine and hydrogen atoms is not corroborated by our investigations on crowded systems. Perfluorination is found to substantially decrease thermal stability, rendering perfluorinated hexamethylethane (C8tBuF) the last potentially stable representative.

Pushing the Limits of Organometallic Redox Chemistry with an Isolable Mn(-I) Dianion.

We report an incredibly reducing and redox-active Mn-I dianion, [Mn(CO)3(Ph2B(tBuNHC)2)]2- (NHC = N-heterocyclic carbene), furnished via 2e- reduction of the parent 16e- MnI complex with Na0 or K0. Cyclic voltammograms show a Mn0/-I redox couple at -3.13 V vs Fc+/0 in tetrahydrofuran (THF), -3.06 V in 1,2-dimethoxyethane, and -2.85 V in acetonitrile. The diamagnetic Mn-I dianion is stable in solution and solid-state at room temperature, tolerating a wide range of countercations ([M(2.2.2)crypt]+, [M(18-crown-6)]+, [nBu4N]+; M = Na, K). Countercation identity does not significantly alter 13C NMR spectral signatures with [nBu4N]+ and Na+, suggesting minimal ion pairing in solution. IR spectroscopy reveals a significant decrease in CO stretching frequencies from MnI to Mn-I (ca. 240 cm-1), consistent with a drastic increase in electron density at Mn. State-of-the-art DFT calculations are in excellent agreement with the observed IR spectral data. Moreover, the Mn-I dianion behaves as a chemical reductant, smoothly releasing 1e- or 2e- to regenerate the oxidized Mn0 or MnI species in solution. The reducing potential of [Mn(CO)3(Ph2B(tBuNHC)2)]2- surpasses the naphthalenide anion in THF (-3.09 V) and represents one of the strongest isolable chemical redox agents.

Flexible Phenanthracene Nanotubes for Explosive Detection.

Phenanthracene nanotubes with arylene-ethynylene-butadiynylene rims and phenanthracene walls are synthesized in a modular bottom-up approach. One of the rims carries hexadecyloxy side chains, mediating the affinity to highly oriented pyrolytic graphite. Molecular dynamics simulations show that the nanotubes are much more flexible than their structural formulas suggest: In 12, the phenanthracene units act as hinges that flip the two macrocycles relative to each other to one of two possible sites, as quantum mechanical models suggest and scanning tunneling microscopy investigations prove. Unexpectedly, both theory and experiment show for 13 that the three phenanthracene hinges are deflected from the upright position, accompanied by a deformation of both macrocycles from their idealized sturdy macroporous geometry. This flexibility together with their affinity to carbon-rich substrates allows for an efficient host-guest chemistry at the solid/gas interface opening the potential for applications in single-walled carbon nanotube-based sensing, and the applicability to build new sensors for the detection of 2,4,6-trinitrotoluene via nitroaromatic markers is shown.

Conformational energies of biomolecules in solution: Extending the MPCONF196 benchmark with explicit water molecules.

A prerequisite for the computational prediction of molecular properties like conformational energies of biomolecules is a reliable, robust, and computationally affordable method usually selected according to its performance for relevant benchmark sets. However, most of these sets comprise molecules in the gas phase and do not cover interactions with a solvent, even though biomolecules typically occur in aqueous solution. To address this issue, we introduce a with explicit water molecules solvated version of a gas-phase benchmark set containing 196 conformers of 13 peptides and other relevant macrocycles, namely MPCONF196 [J. Rezác et al., JCTC 2018, 14, 1254-1266], and provide very accurate PNO-LCCSD(T)-F12b/AVQZ' reference values. The novel solvMPCONF196 benchmark set features two additional challenges beyond the description of conformers in the gas phase: conformer-water and water-water interactions. The overall best performing method for this set is the double hybrid revDSDPBEP86-D4/def2-QZVPP yielding conformational energies of almost coupled cluster quality. Furthermore, some (meta-)GGAs and hybrid functionals like B97M-V and ω B97M-D with a large basis set reproduce the coupled cluster reference with an MAD below 1 kcal mol - 1 . If more efficient methods are required, the composite DFT-method r 2 SCAN-3c (MAD of 1.2 kcal mol - 1 ) is a good alternative, and when conformational energies of polypeptides or macrocycles with more than 500-1000 atoms are in the focus, the semi-empirical GFN2-xTB or the MMFF94 force field (for very large systems) are recommended.

The p-block challenge: assessing quantum chemistry methods for inorganic heterocycle dimerizations.

The elements of the p-block of the periodic table are of high interest in various chemical and technical applications like frustrated Lewis-pairs (FLP) or opto-electronics. However, high-quality benchmark data to assess approximate density functional theory (DFT) for their theoretical description are sparse. In this work, we present a benchmark set of 604 dimerization energies of 302 "inorganic benzenes" composed of all non-carbon p-block elements of main groups III to VI up to polonium. This so-called IHD302 test set comprises two classes of structures formed by covalent bonding and by weaker donor-acceptor (WDA) interactions, respectively. Generating reliable reference data with ab initio methods is challenging due to large electron correlation contributions, core-valence correlation effects, and especially the slow basis set convergence. To compute reference values for these dimerization reactions, after thorough testing, we applied a computational protocol using state-of-the-art explicitly correlated local coupled cluster theory termed PNO-LCCSD(T)-F12/cc-VTZ-PP-F12(corr.). It includes a basis set correction at the PNO-LMP2-F12/aug-cc-pwCVTZ level. Based on these reference data, we assess 26 DFT methods in combination with three different dispersion corrections and the def2-QZVPP basis set, five composite DFT approaches, and five semi-empirical quantum mechanical methods. For the covalent dimerizations, the r2SCAN-D4 meta-GGA, the r2SCAN0-D4 and ωB97M-V hybrids, and the revDSD-PBEP86-D4 double-hybrid functional are found to be the best-performing methods among the evaluated functionals of the respective class. However, since def2 basis sets for the 4th period are not associated to relativistic pseudo-potentials, we obtained significant errors in the covalent dimerization energies (up to 6 kcal mol-1) for molecules containing p-block elements of the 4th period. Significant improvements were achieved for systems containing 4th row elements by using ECP10MDF pseudopotentials along with re-contracted aug-cc-pVQZ-PP-KS basis sets introduced in this work with the contraction coefficients taken from atomic DFT (PBE0) calculations. Overall, the IHD302 set represents a challenge to contemporary quantum chemical methods. This is due to a large number of spatially close p-element bonds which are underrepresented in other benchmark sets, and the partial covalent bonding character for the WDA interactions. The IHD302 set may be helpful to develop more robust and transferable approximate quantum chemical methods in the future.

Confined Lewis Pairs: Investigation of the X- →Si20 Interaction in Halogen-Encapsulating Silafulleranes.

A joint theoretical and experimental study on 32 endohedral silafullerane derivatives [X@Si20 Y20 ]- (X=F-I; Y=F-I, H, Me, Et) and T h ${T_h }$ -[Cl@Si20 H12 Y8 ]- (Y=F-I) is presented. First, we evaluated the structure-determining template effect of Cl- in a systematic series of concave silapolyquinane model systems. Second, we investigated the X- →Si20 interaction energy ( E int ${E_{{\rm{int}}} }$ ) as a function of X- and Y and found the largest E int ${E_{{\rm{int}}} }$ values for electron-withdrawing exohedral substituents Y. Given that X- ions can be considered as Lewis bases and empty Si20 Y20 clusters as Lewis acids, we classify our inseparable host-guest complexes [X@Si20 Y20 ]- as "confined Lewis pairs". Third, 35 Cl NMR spectroscopy proved to be highly diagnostic for an experimental assessment of the Cl- →Si20 interaction as the paramagnetic shielding and, in turn, δ ${\delta }$ (35 Cl) of the endohedral Cl- ion correlate inversely with E int ${E_{{\rm{int}}} }$ . Finally, we disclose the synthesis of [PPN][Cl@Si20 Y20 ] (Y=Me, Et, Br) and provide a thorough characterization of these new silafulleranes.

Computational study of ground-state properties of µ2 -bridged group 14 porphyrinic sandwich complexes.

The structural properties of µ2 -bridged porphyrinic double-decker complexes are investigated and the influence of various ligands, metals, substituents, and bridging atoms on the dominant structural motif is elucidated. A variety of quantum chemical methods including semiempirical (SQM) methods and density functional theory (DFT) is assessed for the calculation of ecliptic and staggered conformational energies. Local coupled cluster (DLPNO-CCSD(T1)) data are generated for reference. The r2 SCAN-3c composite scheme as well as the B2PLYP-D4/def2-QZVPP approach are identified as reliable methods. Energy decomposition analyses (EDA) and localized molecular orbital analyses (LMO) are used to investigate the bonding situation and the nature of the inter-ligand interaction energy underlining the crucial role of attractive London dispersion interactions. Targeted modification of the bridging atom, e.g., by replacing O2- by S2- is shown to drastically change the major structural features of the investigated complexes. Further, the influence of different substituents of varying size at the phthalocyanine ligand regarding the dominant conformation is described.

High-throughput screening of spin states for transition metal complexes with spin-polarized extended tight-binding methods.

The semiempirical GFNn-xTB ( n = 1 , 2 ) tight-binding methods are extended with a spin-dependent energy term (spin-polarization), enabling the fast and efficient screening of different spin states for transition metal complexes. While GFNn-xTB methods inherently can not differentiate properly between high-spin (HS) and low-spin (LS) states, this shortcoming is corrected with the presented methods termed spGFNn-xTB. The performance of spGFNn-xTB methods for spin state energy splittings is evaluated on a newly compiled benchmark set of 90 complexes (27 HS and 63 LS complexes) containing 3d, 4d, and 5d transition metals (termed TM90S) employing DFT references at the TPSSh-D4/def2-QZVPP level of theory. The challenging TM90S set contains complexes with charges between - 4 and +3, spin multiplicities between 1 and 6, and spin-splitting energies that range from - 47.8 to 146.6 kcal/mol with a mean average of 32.2 kcal/mol. On this set the (sp)GFNn-xTB methods, the PM6-D3H4 method, and the PM7 method are evaluated with spGFN1-xTB yielding the lowest MAD of 19.6 kcal/mol followed by spGFN2-xTB with 24.8 kcal/mol. While for the 4d and 5d subsets small or no improvements are observed with spin-polarization, large improvements are obtained for the 3d subset with spGFN1-xTB yielding the smallest MAD of 14.2 kcal/mol followed by spGFN2-xTB with 17.9 kcal/mol and PM6-D3H4 with 28.4 kcal/mol. The correct sign of the spin state splittings is obtained with spGFN2-xTB in 89% of all cases closely followed by spGFN1-xTB with 88%. On the full set, a pure semiempirical vertical spGFN2-xTB//GFN2-xTB-based workflow for screening purposes yields a slightly better MAD of 22.2 kcal/mol due to error compensation, while being qualitative correct for one additional case. In combination with their low computational cost (scanning spin states in seconds), the spGFNn-xTB methods represent robust tools for pre-screening steps of spin state calculations and high-throughput workflows.

Polyradical character assessment using multireference calculations and comparison with density-functional derived fractional occupation number weighted density analysis.

The biradicaloid character of different types of polycyclic aromatic hydrocarbons (PAHs) based on small band gaps is an important descriptor to assess their opto-electronic properties. In this work, the unpaired electron densities and numbers of unpaired electrons (NU values) calculated at the high-level multireference averaged quadratic coupled-cluster (MR-AQCC) method are used to develop a test set to assess the capabilities of different biradical descriptors based on density functional theory. A benchmark collection of 29 different compounds has been selected. The DFT descriptors contain primarily the fractional occupation number weighted electron density (FOD) based on simplified thermally-assisted-occupation density functional theory (TAO-DFT) calculations, but the singlet-triplet energy difference and other descriptors denoted as y0 and nLUNO have been considered as well. After adjustment of the literature-recommended finite temperatures, a very good, detailed agreement between unpaired density and FOD analysis is observed which is also manifested in excellent statistical correlations. The other two descriptors also show good correlations even though the absolute scaling is not satisfactory. A new linear fit of FOD data to the MR-AQCC reference values leads to an improved regression relation for determining the recommended finite temperature value in dependence of the Hartree-Fock exchange. This provides the basis for fast and reliable assessment of the biradical character of many classes of PAHs without the need for performing computationally extended MR calculations.

ωB97X-3c: A composite range-separated hybrid DFT method with a molecule-optimized polarized valence double-ζ basis set.

A new composite density functional theory (DFT) method is presented. It is based on ωB97X-V as one of the best-performing density functionals for the GMTKN55 thermochemistry database and completes the family of "3c" methods toward range-separated hybrid DFT. This method is consistently available for all elements up to Rn (Z = 1-86). Its further key ingredients are a polarized valence double-ζ (vDZP) Gaussian basis set, which was fully optimized in molecular DFT calculations, in combination with large-core effective core potentials and a specially adapted D4 dispersion correction. Unlike most existing double-ζ atomic orbital sets, vDZP shows only small basis set superposition errors (BSSEs) and can compete with standard sets of triple-ζ quality. Small residual BSSE effects are efficiently absorbed by the D4 damping scheme, which overall eliminates the need for an explicit treatment or empirical corrections for BSSE. Thorough tests on a variety of thermochemistry benchmark sets show that the new composite method, dubbed ωB97X-3c, is on par with or even outperforms standard hybrid DFT methods in a quadruple-zeta basis set at a small fraction of the computational cost. Particular strengths of this method are the description of non-covalent interactions and barrier heights, for which it is among the best-performing density functionals overall.

A non-self-consistent tight-binding electronic structure potential in a polarized double-ζ basis set for all spd-block elements up to Z = 86.

Existing semiempirical molecular orbital methods suffer from the usually minimal atomic-orbital (AO) basis set used to simplify the calculations. Here, a completely new and consistently parameterized tight-binding electronic structure Hamiltonian evaluated in a deeply contracted, properly polarized valence double-zeta basis set (vDZP) is described. The inner-shell electrons are accounted for by standard, large-core effective potentials and approximations to them. The primary target of this so-called density matrix tight-binding method is to reproduce the one-particle density matrix P of a molecular ωB97X-V range-separated hybrid density functional theory (DFT) calculation in exactly the same basis set. Additional properties considered are orbital energies, dipole polarizabilities and dipole moments, and dipole polarizability derivatives. The key features of the method are as follows: (a) it is non-self-consistent with an overall fixed number of only three required matrix diagonalizations; (b) only AO overlap integrals are needed to construct the effective Hamiltonian matrix; (c) new P-dependent terms emulating non-local exchange are included; and (d) only element-specific empirical parameters (about 50 per element) need to be determined. The method globally achieves a high accuracy for the target properties at a speedup compared to the ωB97X-V/vDZP reference of about 3-4 orders of magnitude. It performs robustly for difficult transition metal complexes, for highly charged or zwitterionic systems, and for chemically unusual bonding situations, indicating a generally robust approximation of the (self-consistent) Kohn-Sham potential. As an example application, the vibrational Raman spectrum of an entire protein with 327 atoms with respect to the DFT reference calculation is shown. This method may be used out-of-the-box to generate molecular/atomic features for machine learning applications or as the basis for accurate high-speed DFT methods.

An atom-in-molecule adaptive polarized valence single-ζ atomic orbital basis for electronic structure calculations.

Many low-cost or semiempirical quantum mechanical-based electronic structure methods suffer from the use of unpolarized minimal atomic orbital (AO) basis sets. In this work, we overcome this limitation by a fully DFT variationally optimized, adaptive minimal basis set consistently available for the elements up to radon (Z = 86). The new key feature is to make the linear coefficients of the primitive Gaussians in a contracted AO dependent on the effective atomic charge of the atom in the molecule, i.e., each symmetry-unique atom obtains its "own" specifically adapted basis functions. In this way, the physically important "breathing" of the AOs in a molecule with (a) atomic charge (expansion/contraction for anionic/cationic states) and (b) the number of close-lying bonded neighbor atoms is accounted for. The required atomic charges are obtained from a specially developed extended Hückel type Hamiltonian and the coordination numbers from the molecule geometry. Proper analytical derivatives of the resulting adaptive basis functions can easily be derived. Moreover, the basis functions are electric field-dependent, thus improving the description of, e.g., dipole moments and polarizabilities. The new basis set termed q-vSZP (charge dependent valence single-ζ, polarized) is thoroughly benchmarked for atomic/molecular and thermochemical properties compared to standard minimal and double-ζ basis sets at the DFT level with the accurate ωB97X-D4 functional. It is shown that q-vSZP is clearly superior to existing minimal basis sets, often reaching double-ζ quality or even better results. We expect it to be the optimal choice in future semiempirical quantum mechanical methods.

Which outcomes should be measured in hand eczema trials? Results from patient interviews and an expert survey.

BACKGROUND: Hand eczema (HE) is a common skin disease characterized by itch, pain and visible skin changes such as fissures, erythema and vesicles. It is not yet clear which outcome domains are most important for patients. The Hand Eczema Core Outcome Set (HECOS) initiative is developing a consented set of core domains and suitable measurement instruments for the future application in all HE trials. This includes an online Delphi survey about core domains, which requires a 'Long List' of all domains that might be important to measure. OBJECTIVES: To compile a 'Long List' of candidate outcome domains for therapeutic HE trials with suggestions from patients and experts. METHODS: First, 60 patients with chronic HE were interviewed at seven study sites in Croatia, Denmark, Germany, the Netherlands and Spain. Patients were asked about domains that were important from their perspectives. Second, 185 HE experts were invited by email to complete an online survey. With an open question, they were asked to suggest up to six domains. RESULTS: Suggestions were provided by 58 patients and 82 experts. Most patients and experts suggested to measure the domains 'signs', 'symptoms' and 'HE-related quality of life'. Specifically, >25% of patients said that less itch, pain or fissures indicated a successful treatment. Among experts, >25% suggested 'itch' and 'ability to work' as core sub-domains. Further outcomes from the domains 'HE control over time', 'patient-reported treatment experience' and 'skin barrier function' were mentioned. CONCLUSION: 'Itch' was rated high among patients with HE and professional HE experts. While patients emphasized fissures as important, experts underlined the ability to work. This investigation allowed us to define a 'Long List' of 7 candidate outcome domains with 58 sub-domains. From this list, a panel of stakeholders will select core domains during an online Delphi survey.

Dispersion Energy-Stabilized Boron and Phosphorus Lewis Pairs.

An isostructural series of boron/phosphorus Lewis pairs was systematically investigated. The association constants of the Lewis pairs were determined at variable temperatures, enabling the extraction of thermodynamic parameters. The stabilization of the Lewis adduct increased with increasing size of the dispersion energy donor groups, although the donor and acceptor properties of the Lewis pairs remained largely unchanged. This data was utilized to challenge state-of-the-art quantum chemical methods, which finally led to an enhanced workflow for the determination of thermochemical properties of weakly bound Lewis pairs within an accuracy of 0.6 to 1.0 kcal mol-1 for computed association free energies.

Towards understanding solvation effects on the conformational entropy of non-rigid molecules.

The absolute molecular entropy is a fundamental quantity for the accurate description of thermodynamic properties. For non-rigid molecules, a substantial part of the entropy can be attributed to a conformational contribution. Systems and properties where this is relevant, e.g., protein-ligand binding affinities or pKa values refer usually to the liquid phase. In this work, the influence of solvation on the conformational entropy is investigated. A recently introduced state-of-the-art and automated computational protocol for the computation of conformational entropies [Pracht et al., Chem. Sci., 2021, 12, 6551-6568.] is applied in combination with fast and accurate semiempirical quantum-chemical methods and implicit solvation models for a set of 25 commercially available drug molecules and five transition metal compounds. Computed gas-phase conformational entropies are compared with values obtained in implicit n-hexane and water. It is found that implicit solvation can have a substantial effect of several cal mol-1 K-1 on the entropy as a result of large conformational changes in the different phases. We conclude that for flexible molecules chemical accuracy for free energies in solution can only be achieved if solvation effects on the conformational ensemble are considered.

Reliable prediction of association (free) energies of supramolecular complexes with heavy main group elements - the HS13L benchmark set.

We introduce a set of 13 supramolecular complexes featuring diverse non-covalent interactions with heavy main group elements (Zn, As, Se, Te, Br, I), high charges (-2 up to +4), and large systems with up to 266 atoms (HS13L). The experimental Gibbs free energies of association cover the typical range (-1.9 to -9.2 kcal mol-1). An efficient automated multilevel theoretical workflow is applied for the determination of the respective minimum structures in solution by conformer ensemble generation with the CREST program at the semiempirical GFN2-xTB level. Subsequent refinement is performed with the r2SCAN-3c composite DFT method including thermostatistical corrections at the GFN2-xTB level and solvation contributions by COSMO-RS using the CENSO free energy ranking algorithm. Various density functional approximations in combination with three London dispersion correction schemes are assessed against "back-corrected" experimental association energies as well as accurate local coupled cluster reference values. Our protocol predicts association free energies with a mean absolute deviation of only 2 kcal mol-1 from the measured values. Thus, it is well suited to generate reference association free energies for assessing theoretical methods on realistically sized supramolecular complexes or to support experimental chemists. For specifically evaluating methods for calculating gas-phase association energies, we recommend using the provided accurate coupled cluster reference values. We propose to use this set as an extension of the S30L benchmark set [Sure et al., J. Chem. Theory Comput., 2015, 11, 3785-3801] with a special focus on the challenging computation of non-covalent interactions of heavy main group elements.

Conformational Energy Benchmark for Longer n-Alkane Chains.

We present the first benchmark set focusing on the conformational energies of highly flexible, long n-alkane chains, termed ACONFL. Unbranched alkanes are ubiquitous building blocks in nature, so the goal is to be able to calculate their properties most accurately to improve the modeling of, e.g., complex (biological) systems. Very accurate DLPNO-CCSD(T1)/CBS reference values are provided, which allow for a statistical meaningful evaluation of even the best available density functional methods. The performance of established and modern (dispersion corrected) density functionals is comprehensively assessed. The recently introduced r2SCAN-V functional shows excellent performance, similar to efficient composite DFT methods like B97-3c and r2SCAN-3c, which provide an even better cost-accuracy ratio, while almost reaching the accuracy of much more computationally demanding hybrid or double hybrid functionals with large QZ AO basis sets. In addition, we investigated the performance of common wave function methods, where MP2/CBS surprisingly performs worse compared to the simple D4 dispersion corrected Hartree-Fock. Furthermore, we investigate the performance of several semiempirical and force field methods, which are commonly used for the generation of conformational ensembles in multilevel workflows or in large scale molecular dynamics studies. Outstanding performance is obtained by the recently introduced general force field, GFN-FF, while other commonly applied methods like the universal force field yield large errors. We recommend the ACONFL as a helpful benchmark set for parametrization of new semiempirical or force field methods and machine learning potentials as well as a meaningful validation set for newly developed DFT or dispersion methods.

Best-Practice DFT Protocols for Basic Molecular Computational Chemistry.

Nowadays, many chemical investigations are supported by routine calculations of molecular structures, reaction energies, barrier heights, and spectroscopic properties. The lion's share of these quantum-chemical calculations applies density functional theory (DFT) evaluated in atomic-orbital basis sets. This work provides best-practice guidance on the numerous methodological and technical aspects of DFT calculations in three parts: Firstly, we set the stage and introduce a step-by-step decision tree to choose a computational protocol that models the experiment as closely as possible. Secondly, we present a recommendation matrix to guide the choice of functional and basis set depending on the task at hand. A particular focus is on achieving an optimal balance between accuracy, robustness, and efficiency through multi-level approaches. Finally, we discuss selected representative examples to illustrate the recommended protocols and the effect of methodological choices.

[Cl@Si20H20]-: Parent Siladodecahedrane with Endohedral Chloride Ion.

Fullerenes and diamondoids are at the core of nanoscience. Comparable monodisperse silicon analogues are scarce. Herein, we report the synthesis of the parent siladodecahedrane, which represents the largest Platonic solid. It shares its pattern of pentagonal faces with the smallest fullerene, C20, and its saturated, H-terminated skeleton with diamondoids. Similar to endofullerenes, the silicon cage encapsulates a chloride ion ([Cl@Si20H20]-); similar to diamondoids, its Si-H termini offer a wealth of opportunities for further functionalization. Mere treatment with chloromethanes leads to the perchlorinated cluster [Cl@Si20Cl20]-. Both compounds were characterized by mass spectrometry, X-ray crystallography, NMR spectroscopy, and quantum-chemical calculations. The experimentally determined 35Cl resonances of the endohedral chloride ions are particularly diagnostic to probe the Cl- → Si20 interaction strength as a function of the different surface substituents, as we have proven by high-level computational analyses.

Quantification of Noncovalent Interactions in Azide-Pnictogen, -Chalcogen, and -Halogen Contacts.

The noncovalent interactions between azides and oxygen-containing moieties are investigated through a computational study based on experimental findings. The targeted synthesis of organic compounds with close intramolecular azide-oxygen contacts yielded six new representatives, for which X-ray structures were determined. Two of those compounds were investigated with respect to their potential conformations in the gas phase and a possible significantly shorter azide-oxygen contact. Furthermore, a set of 44 high-quality, gas-phase computational model systems with intermolecular azide-pnictogen (N, P, As, Sb), -chalcogen (O, S, Se, Te), and -halogen (F, Cl, Br, I) contacts are compiled and investigated through semiempirical quantum mechanical methods, density functional approximations, and wave function theory. A local energy decomposition (LED) analysis is applied to study the nature of the noncovalent interaction. The special role of electrostatic and London dispersion interactions is discussed in detail. London dispersion is identified as a dominant factor of the azide-donor interaction with mean London dispersion energy-interaction energy ratios of 1.3. Electrostatic contributions enhance the azide-donor coordination motif. The association energies range from -1.00 to -5.5 kcal mol-1 .