The furan microsolvation blind challenge for quantum chemical methods: First steps

© 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

The first microsolvation step for furans : new experiments and benchmarking strategies

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight

Ab initio molecular dynamics simulations of SO 2 solvation in choline chloride/glycerol deep eutectic solvent

International audienceDeep eutectic solvents (DESs) are mixtures of ionic compounds and molecular hydrogen bond donors. Due to the many components and their different interacting subgroups, they give rise to a plethora of many different interactions which can be studied by ab initio molecular dynamics simulations, because within this method all the forces are calculated on the fly and no parametrization prior to the calculation is necessary. Since DESs can be applied in gas capture, for example for SO2 absorption, we performed ab initio molecular dynamics studies of both the pure choline chloride/glycerol DES and the same mixed with SO2. We identified the hydrogen bonding and other specific interactions between all components. With addition of SO2, we observed a decrease in the anion-OH group interplay, because the chloride anions form complexes with the SO2 molecules. Furthermore, the SO2 molecules are incorporated into the hydrophobic network and the interaction between the hydrogen bonds of all OH groups remain constant. This decrease of anion-OH interaction might be responsible for the more fluid state of the SO2-DESs mixture than the pure DES

Basic Phosphonium Ionic Liquids as Wittig Reagents

The possibility of designing a solvent/reagent for Wittig reactions from basic phosphonium salts is explored theoretically. In the suggested R₄P⁺PhO^– and Ph₃PR⁺PhO^– ionic liquids (ILs), the phenolate anion is prone to remove the α-proton from the alkyl chains, forming a phosphorous ylide. Significant hydrogen bonding between the oxygen atoms of the anions and α-hydrogen atoms of the cations were found by molecular dynamics simulations of these substances; therefore, proton transfer between the two ions is inherently supported by the structure of the liquid as well. The subsequent steps of the Wittig reaction from the phosphorous ylide were also found to be energetically possible. The mesoscopic structure of these materials exhibits a significant segregation into polar and nonpolar domains, which may also allow an easy dissolution of the substrates. The formation of a pentacoordinated phosphorous derivative through P–O bond formation was found to be also possible in the gas phase for both kind of compounds. Accordingly, having such basic anions in phosphonium-based ILs may produce such a neutral and therefore volatile species, which may hold further significant applications for these solvents in ion-exchange and separation techniques and in synthesis

Pressure-Dependent Rate Constant Predictions Utilizing the Inverse Laplace Transform: A Victim of Deficient Input Data

<i>k</i>(<i>E</i>) can be calculated either from the Rice–Ramsperger–Kassel–Marcus theory or by inverting macroscopic rate constants <i>k</i>(<i>T</i>). Here, we elaborate the inverse Laplace transform approach for <i>k</i>(<i>E</i>) reconstruction by examining the impact of <i>k</i>(<i>T</i>) data fitting accuracy. For this approach, any inaccuracy in the reconstructed <i>k</i>(<i>E</i>) results from inaccurate/incomplete <i>k</i>(<i>T</i>) description. Therefore, we demonstrate how an improved mathematical description of <i>k</i>(<i>T</i>) data leads to accurate <i>k</i>(<i>E</i>) data. Refitting inaccurate/incomplete <i>k</i>(<i>T</i>), hence, allows for recapturing <i>k</i>(<i>T</i>) information that yields more accurate <i>k</i>(<i>E</i>) reconstructions. The present work suggests that accurate representation of experimental and theoretical <i>k</i>(<i>T</i>) data in a broad temperature range could be used to obtain <i>k</i>(<i>T</i>,<i>p</i>). Thus, purely temperature-dependent kinetic models could be converted into fully temperature- and pressure-dependent kinetic models

Pressure-Dependent Rate Constant Predictions Utilizing the Inverse Laplace Transform: A Victim of Deficient Input Data

<i>k</i>(<i>E</i>) can be calculated either from the Rice–Ramsperger–Kassel–Marcus theory or by inverting macroscopic rate constants <i>k</i>(<i>T</i>). Here, we elaborate the inverse Laplace transform approach for <i>k</i>(<i>E</i>) reconstruction by examining the impact of <i>k</i>(<i>T</i>) data fitting accuracy. For this approach, any inaccuracy in the reconstructed <i>k</i>(<i>E</i>) results from inaccurate/incomplete <i>k</i>(<i>T</i>) description. Therefore, we demonstrate how an improved mathematical description of <i>k</i>(<i>T</i>) data leads to accurate <i>k</i>(<i>E</i>) data. Refitting inaccurate/incomplete <i>k</i>(<i>T</i>), hence, allows for recapturing <i>k</i>(<i>T</i>) information that yields more accurate <i>k</i>(<i>E</i>) reconstructions. The present work suggests that accurate representation of experimental and theoretical <i>k</i>(<i>T</i>) data in a broad temperature range could be used to obtain <i>k</i>(<i>T</i>,<i>p</i>). Thus, purely temperature-dependent kinetic models could be converted into fully temperature- and pressure-dependent kinetic models

Pressure-Dependent Rate Constant Predictions Utilizing the Inverse Laplace Transform: A Victim of Deficient Input Data

<i>k</i>(<i>E</i>) can be calculated either from the Rice–Ramsperger–Kassel–Marcus theory or by inverting macroscopic rate constants <i>k</i>(<i>T</i>). Here, we elaborate the inverse Laplace transform approach for <i>k</i>(<i>E</i>) reconstruction by examining the impact of <i>k</i>(<i>T</i>) data fitting accuracy. For this approach, any inaccuracy in the reconstructed <i>k</i>(<i>E</i>) results from inaccurate/incomplete <i>k</i>(<i>T</i>) description. Therefore, we demonstrate how an improved mathematical description of <i>k</i>(<i>T</i>) data leads to accurate <i>k</i>(<i>E</i>) data. Refitting inaccurate/incomplete <i>k</i>(<i>T</i>), hence, allows for recapturing <i>k</i>(<i>T</i>) information that yields more accurate <i>k</i>(<i>E</i>) reconstructions. The present work suggests that accurate representation of experimental and theoretical <i>k</i>(<i>T</i>) data in a broad temperature range could be used to obtain <i>k</i>(<i>T</i>,<i>p</i>). Thus, purely temperature-dependent kinetic models could be converted into fully temperature- and pressure-dependent kinetic models

An Abnormal N-Heterocyclic Carbene-Carbon Dioxide Adduct from Imidazolium Acetate Ionic Liquids: The Importance of Basicity

In the reaction of 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] ionic liquid with carbon dioxide at 125 8C and 10 MPa, not only the known N-heterocyclic carbene (NHC)–CO2 adduct I, but also isomeric aNHC-CO2 adducts II and III were obtained. The abnormal NHC-O2 adducts are stabilized by the presence of the polarizing basic acetate anion, according to static DFT calculations and ab initio molecular dynamics studies. A further possible reaction pathway is facilitated by the high basicity of the system, deprotonating of the initially formed NHC-CO2 adduct I, which can then be converted in the presence of the excess of CO2 to the more stable 2-deprotonated anionic abnormal NHC–CO2 adduct via the anionic imidazolium-2,4-dicarboxylate according to DFT calculations on model compounds, suggesting a generalizable pathway to abnormal NHC complex formation

Efficient crystal structure prediction for structurally related molecules with accurate and transferable tailor-made force fields

Crystal structure prediction (CSP) has been historically used to complement experimental solid form screening and applied to individual molecules in drug development. The fast development of algorithms and computing resources offers the opportunity to use CSP earlier and for a broader range of applications in the drug design cycle. This study presents a novel paradigm of CSP specifically designed for structurally related molecules, referred to as Quick-CSP. The approach prioritizes more accurate physics through robust and transferable tailor-made force fields (TMFFs), such that significant efficiency gains are achieved through the reduction of expensive ab initio calculations. The accuracy of the TMFF is increased by the introduction of electrostatic multipoles and the fragment-based force field parameterization scheme is demonstrated to be transferable for a family of chemically related molecules. The protocol is benchmarked with structurally related compounds from the Bromodomain and Extraterminal (BET) domain inhibitors series. A new convergence criterion is introduced that aims at performing only as many ab initio optimizations of crystal structures as required to locate the bottom of the crystal energy landscape within a user-defined accuracy. The overall approach provides significant cost savings ranging from three to eight-fold less than the Full-CSP workflow. The reported advancements expand the scope and utility of the underlying CSP building blocks as well as their novel reassembly to other applications earlier in the drug design cycle to guide molecule design and selection