Tanja van Mourik

A critical note on density functional theory studies on rare-gas dimers

In recent literature, some authors claim to have successfully applied density functional theory (DFT) methods to the attractive interaction between rare-gas atoms. In this note, we make a critical survey of these works and come to the conclusion that, in contrast to the claims made, state-of-the-art DFT methods are incapable of accounting for dispersion effects in a quantitative way.

Benchmark full configuration interaction calculations on the helium dimer

Full configuration interaction calculations are presented for the helium dimer employing large basis sets. Using the best basis, which contains up to h‐type basis functions and several closely spaced sets of bond functions, the interaction energy was calculated for a variety of internuclear distances in the range 4.0 to 12.0 bohr. The best calculated values for the He2 interaction energy are −10.947 K at 5.6 bohr (the van der Waals minimum) and +294.90 K at 4.0 bohr (on the repulsive wall). The interaction energy at 4.0 bohr differs significantly from the most recent semiempirical potential of Aziz and Slaman [J. Chem. Phys. 94, 8047 (1991)], indicating that this potential is too attractive around 4.0 bohr. Using a more generally accessible basis, containing only up to f‐type basis functions and only one set of bond functions, the interaction energy was calculated to be −10.903 K at 5.6 bohr and +294.96 K at 4.0 bohr. These results show that functions of higher than f symmetry and bond functions distribut...

Ab initio global potential, dipole, adiabatic, and relativistic correction surfaces for the HCN-HNC system

Ab initio semiglobal potential energy and dipole moment hypersurfaces for the isomerising HCN–HNC system are computed, using a grid of 242 points, principally at the all-electron cc-pCVQZ CCSD(T) level. Several potential energy hypersurfaces (PES) are presented including one which simultaneously fits 1527 points from earlier ab initio, smaller basis CCSD(T) calculations of Bowman et al. [J. Chem. Phys. 99, 308 (1993)]. The resulting potential is then morphed with 17 aug-cc-pCVQZ CCSD(T) points calculated at HNC geometries to improve the representation of the HNC part of the surface. The PES is further adjusted to coincide with three ab initio points calculated, at the cc-pCV5Z CCSD(T) level, at the critical points of the system. The final PES includes relativistic and adiabatic corrections. Vibrational band origins for HCN and HNC with energy up to 12 400 cm−1 above the HCN zero-point energy are calculated variationally with the new surfaces. Band transition dipoles for the fundamentals of HCN and HNC, and a few overtone and hot band transitions for HCN have been calculated with the new dipole surface, giving generally very good agreement with experiment. The rotational levels of ground and vibrationally excited states are reproduced to high accuracy.

Neurotransmitters in the gas phase: a computational and spectroscopic study of noradrenaline

The conformational structures of noradrenaline, isolated in the gas phase, have been explored through a combination of electronic structure computation (at the B3LYP/6-31 + G*, MP2/6-31 + G*, MP2/aug-cc-pVDZ and CIS/6-31 + G* levels of theory) and mass selected ultraviolet and infrared ion dip spectroscopy (following laser ablation of the neurotransmitter into a pulsed supersonic argon expansion). Despite the many possible low-lying conformational possibilities predicted by theory, almost the entire population of jet-cooled noradrenaline adopts the global minimum structure, associated with an extended, AG1a, ethanolamine side chain conformation. Intramolecular hydrogen bonds are formed between the neighbouring hydroxyl groups on the catechol ring and between the hydroxyl and amino groups on the side chain.

Assessment of Density Functionals for Intramolecular Dispersion-Rich Interactions

A range of density functional theory methods, including conventional hybrid and meta-hybrid functionals, a double-hybrid functional, and DFT-D (DFT augmented with an empirical dispersion term) were assessed for their ability to describe the three minima along the ϕGly rotational profile of one particular Tyr-Gly conformer. Previous work had shown that these minima are sensitive to intramolecular dispersion and basis set superposition error, the latter rendering MP2 calculations with small to medium-sized basis sets unsuitable for describing this molecule. Energy profiles for variation of the ϕGly torsion angle were compared to an estimated CCSD(T)/CBS reference profile. The hybrid functionals and the meta-hybrid PWB6K failed to predict all three minima; the meta-hybrid functionals M05-2X and M06-2X and the nonhybrid meta functional M06-L as well as the double-hybrid mPW2-PLYP and the B3LYP-D method did find all three minima but underestimated the relative stability of the two with rotated C-terminus. The best performance was delivered by the most elaborate density functional theory model employed: mPW2-PLYP-D. Only M06-2X and mPW2-PLYP-D predicted the correct order of stability of the three minima.

The structure of the gas-phase tyrosine–glycine dipeptide

The structural preferences of the neutral dipeptide Tyr–Gly have been investigated using a hierarchical selection scheme. This scheme consists of a hierarchy of increasingly more accurate electronic structure methods (single-point HF/3-21G* energy calculation, HF/3-21G* geometry optimization, B3LYP/6-31+G* geometry optimization, MP2/6-31+G* single-point energy calculation, and MP2/6-31+G* geometry optimization). The conformers are sorted according to their single-point or optimized energy, and only the most stable conformers according to one level are taken through to the next level of calculation. The defining structural characteristics in the 20 most stable Tyr–Gly conformers are the presence or absence of a folded arrangement of the peptide backbone (‘book’) and an OH···O hydrogen bond between the C-terminal hydroxyl group and the carbonyl oxygen of tyrosine (‘OHO’). The most stable conformer is of the book/OHO type. MP2 geometry optimization significantly alters the structure of the book-type conformers, increasing their degree of foldedness. Thus, care has to be taken when applying standard density functionals like B3LYP in structural studies of peptides with aromatic side chains.

Synthesis, Conformation and Biological Evaluation of the Enantiomers of 3-Fluoro-γ-Aminobutyric Acid ((R)- and (S)-3F-GABA): An Analogue of the Neurotransmitter GABA

γ‐Aminobutyric acid or GABA (1) is one of the major inhibitory amino acid neurotransmitters of the central nervous system. This article describes the first synthesis of both the (R)‐ and (S)‐ enantiomers of 3‐fluoro‐GABA (2, 3F‐GABA). DFT calculations were carried out in a continuum solvent model (PCM–B3LYP) to estimate the preferred conformations of 3F‐GABA in aqueous solution. NMR coupling constants were calculated for each conformer and were then used to simulate the NMR spectra to evaluate the solution conformation of 3F‐GABA. A preliminary evaluation of the 3F‐GABA enantiomers shows that they act similarly as agonists of cloned GABAA receptors; however, they behave quite differently in a whole animal (Xenopus laevis tadpole model).

NMR spectroscopy: quantum-chemical calculations

The first‐principles computation of nuclear magnetic resonance parameters, in particular chemical shift and spin–spin coupling tensors, is reviewed. After a brief nontechnical introduction into the methodology behind such calculations, selected applications from chemistry and biochemistry in solution and the solid state are highlighted. Special attention is called to cases wherein theory can help in structure determination and refinement, as well as in the interpretation of the observables.

First-Principles Calculation of the Intrinsic Aqueous Solubility of Crystalline Druglike Molecules.

We demonstrate that the intrinsic aqueous solubility of crystalline druglike molecules can be estimated with reasonable accuracy from sublimation free energies calculated using crystal lattice simulations and hydration free energies calculated using the 3D Reference Interaction Site Model (3D-RISM) of the Integral Equation Theory of Molecular Liquids (IET). The solubilities of 25 crystalline druglike molecules taken from different chemical classes are predicted by the model with a correlation coefficient of R = 0.85 and a root mean square error (RMSE) equal to 1.45 log10S units, which is significantly more accurate than results obtained using implicit continuum solvent models. The method is not directly parametrized against experimental solubility data, and it offers a full computational characterization of the thermodynamics of transfer of the drug molecule from crystal phase to gas phase to dilute aqueous solution.

Ab initio and diffusion Monte Carlo study of uracil–water, thymine–water, cytosine–water, and cytosine–(water)2

Optimized geometries, potential well depths, and harmonic zero-point energies of the uracil–water, thymine–water, cytosine–water, and cytosine–(water)2 weakly-bound molecules are computed using second-order Moller–Plesset perturbation theory and an interaction-optimized, singly-polarized double zeta basis set (DZPi). At the optimized geometries of the base–water structures, single point calculations are carried out using the slightly larger ESPB basis set, which is a singly-polarized ‘‘extended s ’’ basis set, containing a set of (s,p) bond functions at the midpoint of each hydrogen bond. All structures are also optimized with a simple intermolecular potential model, consisting of a Lennard–Jones repulsion–dispersion term and a point-charge model for the electrostatic interaction. The ab initio energies are used to assess the realism of the model potential for computing structures and frequencies within the harmonic approximation. The weakness of the harmonic approximation for these weakly bound complexes was assessed by using this potential in rigid-body diffusion Monte Carlo simulations to obtain the anharmonic zero-point energies and vibrationally averaged geometries of the molecular systems investigated. It is found that, although the anharmonicity correction to the zero-point energy is fairly small, the intermolecular bonds are significantly affected by vibrational averaging.