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Frank De Proft

Publications and source records attributed to Frank De Proft.

14 recordsLinked to original sources

Woodward-Hoffmann rules in density functional theory: initial hardness response.

The Woodward-Hoffmann rules for pericyclic reactions, a fundamental set of reactivity rules in organic chemistry, are formulated in the language of conceptual density functional theory (DFT). DFT provides an elegant framework to introduce chemical concepts and principles in a quantitative manner, partly because it is formulated without explicit reference to a wave function, on whose symmetry properties the Woodward-Hoffmann [J. Am. Chem. Soc. 87, 395 (1965)] rules are based. We have studied the initial chemical hardness response using a model reaction profile for two prototypical pericyclic reactions, the Diels-Alder cycloaddition of 1,3-butadiene to ethylene and the addition of ethylene to ethylene, both in the singlet ground state and in the first triplet excited state. For the reaction that is thermally allowed but photochemically forbidden, the initial hardness response is positive along the singlet reaction profile. (By contrast, for the triplet reaction profile, a negative hardness response is observed.) For the photochemically allowed, thermally forbidden reaction, the behavior of the chemical hardness along the initial stages of the singlet and triplet reaction profiles is reversed. This constitutes a first step in showing that chemical concepts from DFT can be invoked to explain results that would otherwise require invoking the phase of the wave function.

Journal Article↗

Hartree-Fock energy partitioning in terms of Hirshfeld atoms.

A Hirshfeld decomposition scheme of the Hartree-Fock total molecular energy into atomic energies is presented. The calculations are performed by direct numerical integration and the results are compared for a set of 28 molecules containing different kinds of atoms. The calculated atomic energies show a strong dependency on changes of atomic electron population and hybridization. Linear correlations are found between the energy and the population for H, these being related to the electronegativity of this atom and to the external potential created by the remaining atoms. The proposed energy partitioning scheme appears to be useful for studies such as proton acidity, the anomeric effect and group transferability, and allows atomic virial ratios to be obtained. Finally, the atomic potential energies are found to mimic trends based on exact expressions as well as trends displayed by molecular quantities, thus lending credibility to the partitioning scheme used.

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Interpretation of hydrogen bonding in the weak and strong regions using conceptual DFT descriptors.

Hydrogen bonding is among the most fundamental interactions in biology and chemistry, providing an extra stabilization of 1-40 kcal/mol to the molecular systems involved. This wide range of stabilization energy underlines the need for a general and comprehensive theory that will explain the formation of hydrogen bonds. While a simple electrostatic model is adequate to describe the bonding patterns in the weak and moderate hydrogen bond regimes, strong hydrogen bonds, on the other hand, require a more complete theory due to the appearance of covalent interactions. In this study, conceptual DFT tools such as local hardness, eta(r) and local softness, s(r), have been used in order to get an alternative view on solving this hydrogen-bonding puzzle as described by Gilli et al. [J. Mol. Struct. 2000, 552, 1]. A series of both homonuclear and heteronuclear resonance-assisted hydrogen bonds of the types O-H...N, N-H...O, N-H...N, and O-H...O with strength varying from weak to very strong have been studied. First of all, DeltaPA and DeltapK(a) values were calculated and correlated to the hydrogen bond energy. Then the electrostatic effects were examined as hard-hard interactions accessible through molecular electrostatic potential, natural population analysis (NPA) charge, and local hardness calculations. Finally, secondary soft-soft interaction effects were entered into the picture described by the local softness values, providing insight into the covalent character of the strong hydrogen bonds.

Acrylates↗

Study of molecular quantum similarity of enantiomers of amino acids.

Molecular quantum similarity is evaluated for enantiomers in the case of molecules showing conformational flexibility, using our earlier proposed Boltzmann weighted similarity index. The conformers of the enantiomers of the amino acids alanine, asparagine, cysteine, leucine, serine, and valine were examined. Next to studying global indices, the evaluation of local similarity is carried out using our earlier proposed local similarity index based on the Hirshfeld partitioning, to further illustrate Mezey's holographic electron density theorem in chiral systems and to quantify dissimilarity of enantiomers.

Amino Acids↗

Hardness and softness reactivity kernels within the spin-polarized density-functional theory.

Generalized hardness and softness reactivity kernels are defined within a spin-polarized density-functional theory (SP-DFT) conceptual framework. These quantities constitute the basis for the global, local (i.e., r-position dependent), and nonlocal (i.e., r and r'-position dependents) indices devoted to the treatment of both charge-transfer and spin-polarization processes in such a reactivity framework. The exact relationships between these descriptors within a SP-DFT framework are derived and the implications for chemical reactivity in such context are outlined.

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Computation of the hardness and the problem of negative electron affinities in density functional theory.

The absolute hardness in density functional theory (DFT) is discussed, emphasizing the charge-transfer excitation interpretation. Direct evaluation from the computed ionization potential and electron affinity is intrinsically problematic when the affinity is negative; the calculated affinity exhibits a strong basis set dependence, becoming near zero as diffuse functions are added. An alternative Koopmans-based approximation using local functional eigenvalues uniformly and significantly underestimates the hardness. A simple correction to the Koopmans expression is highlighted on the basis of a consideration of the integer discontinuity. The resulting hardness expression does not require the explicit computation of the affinity and has a straightforward interpretation in terms of the electronegativity. The correction eliminates the underestimation and gives hardness values that do not degrade as the electron affinity becomes more negative. For systems with large negative affinities, the values are an improvement over those from the other approaches. The success can be traced to an implicit, unconventional approximation for the electron affinity, which outperforms the standard approach when the affinity is significantly negative and which does not break down as the basis set becomes more diffuse.

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Stiffness and Raman intensity: a conceptual and computational DFT study.

A DFT-based reactivity descriptor, the nuclear stiffness, is related to the Raman scattering intensity, which is experimentally accessible. The application of this new relationship obtained within certain approximations has been checked in two different sets of molecules. First, we study a favorable case, where the contribution of the anisotropy to the Raman intensity is zero (symmetric stretching mode in 15 tetrahedral molecules). Second, we consider a "worst" case scenario, where the anisotropy contribution can be expected to be important (stretching mode in 32 diatomic molecules). The numerical results clearly show a relationship between stiffness and Raman intensity reflecting the expected anisotropy influence.

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Comprehensive study of density functional theory based properties for group 14 atoms and functional groups, -XY3 (X = C, Si, Ge, Sn, Pb, Element 114; Y = CH3, H, F, Cl, Br, I, At).

All electron nonrelativistic and relativistic density functional theory calculations at the BP86/QZ4P (Slater type) level are reported for a set of fundamentally useful DFT based reactivity descriptors for group 14 elements (C, Si, Ge, Sn, Pb, Element 114 (abbreviated as Uuq)) and functional groups, -XY3 (X = C, Si, Ge, Sn, Pb, Element 114 (Uuq); Y = CH3, H, F, Cl, Br, I, At); these include electronegativity (chi), chemical hardness (eta), global softness (S), and electrophilicity index (omega). This approach permits an evaluation of the discrepancies in electronegativity scales and associated properties at uniform levels affording a nonempirical analysis for the first time. The vital importance of the spin-orbit interaction, in addition to the scalar relativistic terms, is demonstrated in reproducing the experimental trends on going from top to bottom of the group. The order for isolated atoms is altered when passing to -XY3 groups for all of the properties studied. For example, the calculated atomic electronegativities show a uniform decrease from C to Pb increasing again to Uuq as verified in the experimental data for C-Pb but at variance with several other scales. The sequence for functional groups is different and in accordance with experimental NMR data where available. The experimental hardness sequence for the isolated atoms (C > Pb > Si > Ge > Sn) is opposed to the trends of decreasing hardness on going down the periodic table as is found, e.g., in the halogen group and confirmed by this study. The -XY3 functional groups however follow the C > Si > Ge > Sn > Pb sequence. The recently developed electrophilicity index (omega) has been shown to be highly correlated with the electron affinity rather than the electronegativity. Finally, regression analyses that discriminate between the properties are carried out to investigate the nature of additivity of atomic contributions in functional group properties.

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Hard-soft acid-base interactions of silylenes and germylenes.

A detailed investigation of the electrophilic and nucleophilic character of singlet silylenes and germylenes, divalent compounds of silicon and germanium, respectively, substituted by first- and second-row elements is presented. In a first part, the Lewis acid properties of these compounds were studied through their complexation reaction with the Lewis bases NH3, PH3, and AsH3. The results indicate that this complexation is most favorable with the hardest base NH3, classifying these compounds as hard Lewis acids. This is confirmed by the linear correlation between the interaction energies and the value of the electrostatic potential, used as an approximation to the local hardness, near the empty p orbital of these compounds, indicating a charge-controlled interaction in the complex. Also the electrophilicity index, proposed by Parr et al., computed both at the global and the local level, correlates linearly with the complexation energies of the compounds with NH3. The Lewis base character of these silylenes has been investigated, through their interaction with the acids BH3 and AlH3. Also in this case, the electrostatic potential can be used to probe the reactivity of the compounds. It will finally be demonstrated that an increasing stability of the silylenes and germylenes is accompanied by an increase in their nucleophilicity and a decrease of the electrophilicity.

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Gas-phase stability of tetrahedral multiply charged anions: a conceptual and computational DFT study.

Multiply charged anions (MCA's) are unstable relative to electron autoejection; however, the repulsive Coulomb barrier (RCB) provides electronic stability. In view of their interest in biological systems, the behavior of isolated AsO(4)(3-), PO(4)(3-), SO(4)(2-), and SeO(4)(2-) in the gas phase and in solution has been studied. To calculate the RCB values, the electrostatic and point charge model-two methods currently used in the literature-are applied, together with a recently introduced Conceptual Density Functional Theory (DFT) based approach. The relative stability of the above-mentioned MCA's is compared. The trends of the RCB are analyzed by including analogous compounds from the second and third row and by passing from dianionic to trianionic systems. Considering the effect of solvent, using the SCI-PCM solvent model, the evolution of the RCB when passing to higher dielectric constants is evaluated. The RCB is related to the properties of the system as polarizability/softness. Both a numerical and a conceptual correlation between the RCB and the global softness is found.

Anions↗

Ring currents as probes of the aromaticity of inorganic monocycles : P5-, As5-, S2N2, S3N3-, S4N3+, S4N42+, S5N5+, S42+ and Se42+.

Current-density maps were calculated by the ipsocentric CTOCD-DZ/6-311G** (CTOCD-DZ=continuous transformation of origin of current density-diamagnetic zero) approach for three sets of inorganic monocycles: S(4) (2+), Se(4) (2+), S(2)N(2), P(5) (-) and As(5) (-) with 6 pi electrons; S(3)N(3) (-), S(4)N(3) (+) and S(4)N(4) (2+) with 10 pi electrons; and S(5)N(5) (+) with 14 pi electrons. Ipsocentric orbital analysis was used to partition the currents into contributions from small groups of active electrons and to interpret the contributions in terms of symmetry- and energy-based selection rules. All nine systems were found to support diatropic pi currents, reinforced by sigma circulations in P(5) (-), As(5) (-), S(3)N(3) (-), S(4)N(3) (+), S(4)N(4) (2+) and S(5)N(5) (+), but opposed by them in S(4) (2+), Se(4) (2+) and S(2)N(2). The opposition of pi and sigma effects in the four-membered rings is compatible with height profiles of calculated NICS (nucleus-independent chemical shifts).

Journal Article↗

Ab initio study of the binding of Trichostatin A (TSA) in the active site of histone deacetylase like protein (HDLP).

Histone deacetylase (HDAC) inhibitors have recently attracted considerable interest because of their therapeutic potential for the treatment of cell proliferative diseases. An X-ray structure of a very potent inhibitor, Trichostatin A (TSA), bound to HDLP (an HDAC analogue isolated from Aquifex aeolicus), is available. From this structure, an active site model (322 atoms), relevant for the binding of TSA and structural analogues, has been derived, and TSA has been minimized in this active site at HF 3-21G* level. The resulting conformation is in excellent accordance with the X-ray structure, and indicates a deprotonation of the hydroxamic acid in TSA by His 131. Also, a water molecule was minimized in the active site. In addition to a similar deprotonation, in accordance with a possible catalytic mechanism of HDAC as proposed by Finnin et al. (M. S. Finnin, J. R. Donigian, A. Cohen, V. M. Richon, R. A. Rifkind and P. A. Marks, Nature, 1999, 401, 188-193), a displacement of the resulting OH- ion in the active site was observed. Based on these results, the difference in energy of binding between TSA and water was calculated. The resulting value is realistic in respect to experimental binding affinities. Furthermore, the mechanism of action of the His 131-Asp 166 charge relay system was investigated. Although the Asp residue in this motif is known to substantially increase the basicity of the His residue, no proton transfer from His 131 to Asp 166 was observed on binding of TSA or water. However, in the empty protonated active site, this proton transfer does occur.

Bacterial Proteins↗

Magnetic properties and aromaticity of o-, m-, and p-benzyne.

The relative aromaticities of the three singlet benzyne isomers, 1,2-, 1,3-, and 1,4-didehydrobenzenes have been evaluated with a series of aromaticity indicators, including magnetic susceptibility anisotropies and exaltations, nucleus-independent chemical shifts (NICS), and aromatic stabilization energies (all evaluated at the DFT level), as well as valence-bond Pauling resonance energies. Most of the criteria point to the o-benzyne<m-benzyne<p-benzyne aromaticity order, whereas the relative aromaticity of each isomer with respect to benzene depends on the aromaticity criterion. An additional aromaticity evaluation involved the transition state of the Bergman cyclization of (Z)-hexa-1,5-diyn-3-ene which yields p-benzyne. Dissected NICS calculations reveal an aromatic transition state with a larger total NICS but a smaller NICS(pi) component and thus lower aromaticity than benzene.

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The Basicity of p-Substituted Phenolates and the Elimination-Substitution Ratio in p-Nitrophenethyl Bromide: A HSAB Theoretical Study.

The influence of basicity in a set of para-substituted phenolates on the elimination-substitution ratio obtained upon reaction with p-nitrophenethyl bromide has been studied. A correlation between experimental equilibrium data (pK(a)) and reactivity indices obtained from density functional theory (DFT) was looked for in order to show that the hard and soft acids and bases principle (HSAB) is well suited to describe the basicity properties of the para-substituted phenolates. When the basicity of para-substituted phenolates increases, their global hardness and their condensed softness at the oxygen atom increase; the negative net charge, condensed nucleophilic fukui function, and condensed nucleophilic softness of the oxygen atom increase. The proposal that the alkyl halide substrate possesses a hard beta-hydrogen atom and a soft alpha-carbon was studied for p-nitrophenethyl bromide; it turns out that the beta-hydrogen atom is soft, even softer than the carbon atom. The experimental results for the elimination-substitution ratio for p-nitrophenethyl bromide can be explained from a local-local HSAB viewpoint for the para-substituted phenolates and p-nitrophenethyl bromide and not from a global-local level viewpoint as suggested before. The results suggest that para-substituted phenolates with higher basicity (harder), less delocalized negative charge into the fragment R-C(6)H(4), and a more polarizable oxygen atom (softer) do have a lower (relative) attraction toward an alkyl carbon atom (soft) than toward a hydrogen atom (softer) from p-nitrophenethyl bromide. The beta-hydrogen and alpha-carbon atoms can be considered to act as a Lewis acid toward the para-substituted phenolate nucleophile considered as a base.

Journal Article↗