Investigations into the Nature of Halogen Bonding Including Symmetry Adapted Perturbation Theory Analyses

In recent years it has been recognized that, because of their unique properties, halogen bonds have tremendous potential in the development of new pharmaceutical compounds and materials. In this study we investigate the phenomenon of halogen bonding by carrying out ab initio calculations on the halomethane-formaldehyde complexes as well as the fluorine substituted FnH3-nCX···OCH2 dimers, where the halogen bonding halogens (X) are chlorine, bromine, and iodine. Coupled cluster (CCSD(T)/aug-cc-pVTZ) calculations indicate that the binding energies for these type of interactions lie in the range between −1.05 kcal/mol (H3CCl···OCH2) and −3.72 kcal/mol (F3CI···OCH2). One of the most important findings in this study is that, according to symmetry adapted perturbation theory (SAPT) analyses, halogen bonds are largely dependent on both electrostatic and dispersion type interactions. As the halogen atom involved in halogen bonding becomes larger the interaction strength for this type of interaction also gets larger and, interestingly, more electrostatic (and less dispersive) in character. Halogen bonding interactions also become stronger and more electrostatic upon substitution of (the very electronegative) fluorines onto the halomethane molecule

Assessment of Density Functional Theory Methods for the Computation of Heats of Formation and Ionization Potentials of Systems Containing Third Row Transition Metals

The performance of several different density functional theory (DFT) methods, including GGA, hybrid-GGA, meta-GGA, and hybrid-meta-GGA methods, have been assessed in terms of their ability to accurately compute both heats of formation and ionization potentials of systems containing third row transition metals. Two different basis sets were used in this study:  6-31G** and TZVP. It is found that the triple-ζ quality TZVP basis set generally produces the best results for both heats of formation and ionization potentials. One important observation made in this study is that the inclusion of exact exchange terms in DFT methods generally results in more consistently accurate results for both heats of formation and ionization potentials of transition metal systems. In general, DFT methods do not yield good ionization potential results for systems containing titanium or zinc. For heats of formation, it is found that the hybrid-meta-GGA functional, TPSS1KCIS, yields the best overall results when combined with the TZVP basis set, while PBE1PBE (hybrid-GGA) gives the best results for the 6-31G** basis. The hybrid-GGA functional, B3LYP, is found to produce the lowest overall errors for ionization potentials when combined with both 6-31G** and TZVP

Strength and Character of Halogen Bonds in Protein–Ligand Complexes

In this study we investigate the strength and character of eight halogen bonding interactions from six protein–ligand complexes. The halogen bonding complexes investigated here were selected because of their favorable halogen bond characteristics. Interaction energies of model systems derived from protein–ligand complexes are computed at the MP2/aug-cc-pVDZ level of theory, and the relative contributions of electrostatics and dispersion are estimated by computing ΔE(HF)/ΔE(MP2) ratios. The relationship between these ratios and DFT-SAPT Eelec/Edisp results is calibrated using smaller model systems in order to gain a qualitative understanding of the relative roles that electrostatics and dispersion play in these halogen bonds. Electrostatic potentials for the halogen bonding ligands are also generated in order to study the relationship between halogen bond strengths and halogen σ-hole size (and charge). It is found that the strength and character of the protein–ligand halogen bonds investigated here are strongly dependent on geometric factors and σ-hole characteristics. Many of the halogen bonds studied here, especially those with favorable geometric and electrostatic properties, are found to be of sufficient magnitude to make significant contributions to protein–ligand binding

Insights into the Strength and Origin of Halogen Bonding: The Halobenzene−Formaldehyde Dimer

The observation of short halogen−carbonyl oxygen interactions in protein−ligand complexes has spurred us to use computational tools to better understand the strength of halogen bonding interactions. In this study we have produced potential energy curves for the halogen bonding interactions of several halobenzene−formaldehyde complexes. It was found that, for most halogen substituents, a halobenzene and formaldehyde form stable halogen bonded complexes with interaction energies that increase as the size of the halogen substituent increases

Assessment of Density Functional Theory Methods for the Computation of Heats of Formation and Ionization Potentials of Systems Containing Third Row Transition Metals

The performance of several different density functional theory (DFT) methods, including GGA, hybrid-GGA, meta-GGA, and hybrid-meta-GGA methods, have been assessed in terms of their ability to accurately compute both heats of formation and ionization potentials of systems containing third row transition metals. Two different basis sets were used in this study:  6-31G** and TZVP. It is found that the triple-ζ quality TZVP basis set generally produces the best results for both heats of formation and ionization potentials. One important observation made in this study is that the inclusion of exact exchange terms in DFT methods generally results in more consistently accurate results for both heats of formation and ionization potentials of transition metal systems. In general, DFT methods do not yield good ionization potential results for systems containing titanium or zinc. For heats of formation, it is found that the hybrid-meta-GGA functional, TPSS1KCIS, yields the best overall results when combined with the TZVP basis set, while PBE1PBE (hybrid-GGA) gives the best results for the 6-31G** basis. The hybrid-GGA functional, B3LYP, is found to produce the lowest overall errors for ionization potentials when combined with both 6-31G** and TZVP

Role of Solvation in the Energy Stabilization Inside the Hydrophobic Core of the Protein Rubredoxin

There are many forces that contribute to the stability of a protein; among these are dispersion interactions, hydrogen bonding, and solvation effects. In a recent work, Vondrásek et al. estimated the in vacuo stabilization energy of the hydrophobic core of the protein rubredoxin using high level ab initio methods (Vondrásek, J.; et al. J. Am. Chem. Soc. 2005, 127, 2615). In this work, we evaluate the effects of solvation on the stability of the hydrophobic core of this protein. Solvation calculations are made using the polarizable continuum method at the MP2/aug-cc-pVDZ level of theory. It is found that, in a protein-like environment (mimicked by a continuum solvent with a dielectric constant of ∼4), the stability of rubredoxin's hydrophobic core is decreased by 40−50%. We also observed that the stabilization energy of the hydrophobic core is only slightly lower in a protein-like medium than in an aqueous one (ΔGether − ΔGwater ≈ 1.0−3.5 kcal/mol)

Assessment of Density Functional Theory Methods for the Computation of Heats of Formation and Ionization Potentials of Systems Containing Third Row Transition Metals

The performance of several different density functional theory (DFT) methods, including GGA, hybrid-GGA, meta-GGA, and hybrid-meta-GGA methods, have been assessed in terms of their ability to accurately compute both heats of formation and ionization potentials of systems containing third row transition metals. Two different basis sets were used in this study:  6-31G** and TZVP. It is found that the triple-ζ quality TZVP basis set generally produces the best results for both heats of formation and ionization potentials. One important observation made in this study is that the inclusion of exact exchange terms in DFT methods generally results in more consistently accurate results for both heats of formation and ionization potentials of transition metal systems. In general, DFT methods do not yield good ionization potential results for systems containing titanium or zinc. For heats of formation, it is found that the hybrid-meta-GGA functional, TPSS1KCIS, yields the best overall results when combined with the TZVP basis set, while PBE1PBE (hybrid-GGA) gives the best results for the 6-31G** basis. The hybrid-GGA functional, B3LYP, is found to produce the lowest overall errors for ionization potentials when combined with both 6-31G** and TZVP

Assessment of Density Functional Theory Methods for the Computation of Heats of Formation and Ionization Potentials of Systems Containing Third Row Transition Metals

The performance of several different density functional theory (DFT) methods, including GGA, hybrid-GGA, meta-GGA, and hybrid-meta-GGA methods, have been assessed in terms of their ability to accurately compute both heats of formation and ionization potentials of systems containing third row transition metals. Two different basis sets were used in this study:  6-31G** and TZVP. It is found that the triple-ζ quality TZVP basis set generally produces the best results for both heats of formation and ionization potentials. One important observation made in this study is that the inclusion of exact exchange terms in DFT methods generally results in more consistently accurate results for both heats of formation and ionization potentials of transition metal systems. In general, DFT methods do not yield good ionization potential results for systems containing titanium or zinc. For heats of formation, it is found that the hybrid-meta-GGA functional, TPSS1KCIS, yields the best overall results when combined with the TZVP basis set, while PBE1PBE (hybrid-GGA) gives the best results for the 6-31G** basis. The hybrid-GGA functional, B3LYP, is found to produce the lowest overall errors for ionization potentials when combined with both 6-31G** and TZVP

Extensions of the S66 Data Set: More Accurate Interaction Energies and Angular-Displaced Nonequilibrium Geometries

We present two extensions of the recently published S66 data set [Řezáč, Riley, Hobza; DOI: 10.1021/ct2002946]. Interaction energies for the equilibrium geometry complexes have been recalculated using a triple-ζ basis set for the CCSD(T) term in the CCSD(T)/CBS scheme. This allows for the extrapolation of this term to the complete basis set limit, improving accuracy by almost 1 order of magnitude compared to the scheme previously used for the S66 set. Now, we estimate the largest error in the set to be about 1%. Validation of several methods against the new data indicates the exceptional robustness and accuracy of the SCS-MI-CCSD method. The second extension improves the coverage of nonequilibrium geometries. We introduce a new data set, S66a8, that samples intermolecular angular degrees of freedom in the S66 complexes. For each of the 66 complexes, eight displaced geometries have been constructed, systematically sampling possible rotations of the monomers. Interaction energies in this set are calculated at the CCSD(T)/CBS level consistently with the earlier introduced S66x8 data set that samples the intermolecular distance

Extensions of the S66 Data Set: More Accurate Interaction Energies and Angular-Displaced Nonequilibrium Geometries

We present two extensions of the recently published S66 data set [Řezáč, Riley, Hobza; DOI: 10.1021/ct2002946]. Interaction energies for the equilibrium geometry complexes have been recalculated using a triple-ζ basis set for the CCSD(T) term in the CCSD(T)/CBS scheme. This allows for the extrapolation of this term to the complete basis set limit, improving accuracy by almost 1 order of magnitude compared to the scheme previously used for the S66 set. Now, we estimate the largest error in the set to be about 1%. Validation of several methods against the new data indicates the exceptional robustness and accuracy of the SCS-MI-CCSD method. The second extension improves the coverage of nonequilibrium geometries. We introduce a new data set, S66a8, that samples intermolecular angular degrees of freedom in the S66 complexes. For each of the 66 complexes, eight displaced geometries have been constructed, systematically sampling possible rotations of the monomers. Interaction energies in this set are calculated at the CCSD(T)/CBS level consistently with the earlier introduced S66x8 data set that samples the intermolecular distance