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Patrick Bultinck

Publications and source records attributed to Patrick Bultinck.

18 recordsLinked to original sources
PubMed2007

Aromaticity in linear polyacenes: generalized population analysis and molecular quantum similarity approach.

The relative aromaticity of benzenoid rings in the linear polyacenes is investigated using two novel aromaticity approaches. According to the first, the aromaticity of individual benzene rings was gauged by the values of six-center bond indices (SCI) calculated within the so-called Generalized Population Analysis (GPA). In the second approach, the same goal is addressed using the theory of Molecular Quantum Similarity (MQS). Both independent approaches are found to correlate very well, and both point toward decreasing aromaticity in any linear polyacenes upon going from the outer to inner rings.

Journal Article↗
PubMed2007

Aromaticity and Homoaromaticity in Methano[10]annulenes.

Aromaticity and neutral homoaromaticity have been evaluated in methano[10]annulenes systems, 1,4-methano[10]annulene (1), 1,5-methano[10]annulene (2), and 1,6-methano[10]annulene (3). C-C bond lengths indicate that 1 presents higher bond alternation than 2 and 3. The relative energies were determined at the B3LYP/6-311+G(d,p) level, and they pointed out that 3 is the most stable isomer. Strain energies, evaluated employing homodesmotic reactions, show the same order as the relative energies. Through a decomposition of strain energies, it could be concluded that the rings absorb more tension than the bridges. The changes in aromaticity were evaluated by magnetic susceptibilities, chiM, HOMA, NICS, and resonance energies, RE. HOMA, RE, and chiM indicate that 2 and 3 are strongly, and 1 is fairly, aromatic. NICS does not provide reliable results, due to interference of ring and bridge atoms. NBO analysis presents some interactions that suggest the existence of neutral homoaromaticity. GPA indices (evaluated at the B3LYP/6-31G* level) point out that homoaromaticity plays a relevant role only in 3. Moreover, this work is the first in the current literature that studies 1,4-methano[10]annulene (1).

Journal Article↗
PubMed2006

Unrevealed structural requirements for auxin-like molecules by theoretical and experimental evidences.

An computational-biostatistical approach, supported by ab initio optimizations of auxin-like molecules, was used to find biologically meaningful relationships between quantum chemical variables and fresh bioassay's data. It is proven that the auxin-like recognition requires different molecular assembling states. We suggest that the carboxyl group is not the determining factor in explaining the biological auxin-like conduct. The biological effects depends essentially on the chemical condition of the ring system. The aim to find active molecules (quantum objects) via statistical grouping-analysis of molecular quantum similarity measures was verified by bioactivity assays. Next, this approach led to the discovery of a non-carboxylated active auxin-like molecule (2,6-dibromo-phenol). This is the first publication on structure activity relationship of auxin-like molecules, which relies on highly standardized bioassays of different auxins screened in parallel as well as analysed by multi-dimensional scaling.

Biological Assay↗
PubMed2006

Local aromaticity in polycyclic aromatic hydrocarbons: electron delocalization versus magnetic indices.

The local aromaticity of benzenoid rings is examined by means of the Polansky index (P) and generalized population analysis (GPA). The results are found to agree very well with recently published circuit-condensed ring currents and magnetic-energetic aromaticity indices, but no correlation is found with nucleus independent chemical shifts (NICS). This is usually seen as a manifestation of the more general multidimensional nature of aromaticity. This paper examines the sources for the observed correlations, showing that some indices give conflicting results because they inherently reflect different phenomena.

Journal Article↗
PubMed2006

Intermolecular association of tetrahydrofuran-2-carboxylic acid in solution: a vibrational circular dichroism study.

Carboxylic acids are known for their strong intermolecular associations. With chiral carboxylic acids, this behavior can be studied using vibrational circular dichroism (VCD). Tetrahydrofuran-2-carboxylic acid 1, a chiral building block for beta-lactam antibiotics, is studied by emphasizing the effect of the dimerization. Experimental results indicate that for solutions of 1 in CDCl3 and CS2, a complex equilibrium exists between the monomers and dimers. B3LYP/aug-cc-pVTZ calculations are performed on both monomer and dimer structures. To simulate IR and VCD spectra, populations for monomer and dimers were approximated using a semiquantitative model. A good agreement between experimental and simulated spectra is obtained by taking into account both the monomeric and the dimeric structures, weighted using the experimentally determined populations.

Carboxylic Acids↗
PubMed2006

A DFT conformational analysis and VCD study on methyl tetrahydrofuran-2-carboxylate.

DFT calculations were performed on (S)-methyl tetrahydrofuran-2-carboxylate to facilitate the interpretation of IR and VCD spectra. The potential energy surface could not be described unambiguously using the 6-31G* basis set in combination with different density functionals including B1LYP, B3LYP, B3P86, B3PW91, B98, BHandH, BHandHLYP, MPW1PW91 and PBE1PBE. In contrast, a uniform conformational picture could be found using the cc-pVTZ basis set. Using this large basis set and the collection of nine functionals from above, the dipole and rotational strengths were calculated, and compared to experimental values which were extracted from the experimental IR and VCD spectra for (+)-(S)-methyl tetrahydrofuran-2-carboxylate. A detailed analysis on the agreement between experiment and simulated spectra was performed by assigning the experimental bands based on the harmonic fundamentals obtained for all functionals except BHandH, which performs badly over the whole line. Assessing the dipole strengths, all tested functionals perform equally well. For the rotational strengths, differences can be observed: B3LYP, B1LYP and B98 give the highest correlation with experiment, while PBE1PBE gives the lowest correlation. Comparable conclusions are obtained using a neighborhood similarity measure.

Circular Dichroism↗
PubMed2006

Electron delocalization and aromaticity in linear polyacenes: atoms in molecules multicenter delocalization index.

Molecular aromaticity in the linear polyacenes is investigated using an atoms in molecules based six center index (SCI-AIM) which measures the electron delocalization. SCI-AIM values for the linear polyacenes indicate decreasing aromaticity going from outer to inner rings in the polyacene series. The SCI-AIM approach is compared to a Mulliken-like approach, and a critical comparison to the PDI index is made.

Journal Article↗
PubMed2006

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↗
PubMed2006

Multicenter bonding in carbocations with tetracoordinate protons.

The nature of the bonding in a set of nonclassical carbocations with tetracoordinated protons "sandwiched" between two C=C pi bonds was scrutinized using the new computational methodology of generalized population analysis. The results of this theoretical analysis strongly corroborate the conclusions of a previous study in which the occurrence of delocalized 5-center 4-electron (5c-4e) bonding in the C-C-H-C-C fragments of such cations was anticipated.

Journal Article↗
PubMed2006

Elucidation of the absolute configuration of JNJ-27553292, a CCR2 receptor antagonist, by vibrational circular dichroism analysis of two precursors.

The absolute configurations of two precursors, that is, 1-(3',4'-dichlorophenyl)-propanol and 1-(3',4'-dichlorophenyl)-propanamine, of a potent 2-mercapto-imidazole CCR-2 receptor antagonist, JNJ-27553292, were determined using vibrational circular dichroism. As a consequence, the absolute configuration of the antagonist itself was also determined. The two precursor compounds were subjected to a thorough conformational analysis and rotational strengths were calculated at the B3LYP/cc-pVTZ level of theory. Based on these data, vibrational circular dichroism spectra were simulated, which in turn were compared with experimental spectra. Agreement between the spectra allowed the assignment of the absolute configuration, which is in agreement with the proposed configuration based on stereospecific reactions on similar compounds.

Circular Dichroism↗
PubMed2005

Multicenter bond indices as a new means for the quantitative characterization of homoaromaticity.

This study reports the use of multicenter bond indices as a new tool for the quantitative characterization of homoaromaticity. The approach was applied to the series bicyclic systems whose homoaromaticity was recently discussed in terms of traditional aromaticity index, namely, NICS. In this study we found that the multicenter bond indices are indeed able to quantify the degree of homoaromaticity of the studied systems as reflected in the classification of these molecules into classes of homoaromatic, non-homoaromatic, and anti-homoaromatic systems suggested on the basis of NICS values.

Models, Chemical↗
PubMed2003

Role of solution conformation and flexibility of short peptide ligands that bind to the p56(lck) SH2 domain.

A general approach in drug design is making ligands more rigid in order to avoid loss in conformational entropy (deltaS(conf)) upon receptor binding. We hypothesized that in the high affinity binding of pYEEI peptide ligands to the p56(lck) SH2 domain this loss in deltaS(conf) might be diminished due to preorganization of the fourfold negatively charged pYEEI peptide in the bound, extended, conformation. A thermodynamic analysis was performed on the peptides Ac-pYEEI-NH(2), Ac-pYAAI-NH(2) and Ac-pYGGI-NH(2) using surface plasmon resonance (SPR) competition experiments to assay affinity constants at different temperatures. To study the effect of solution conformation and flexibility a computational conformation analysis was performed from which low energy conformations in solution were calculated, and S(conf) estimated. It was found that the calculated low energy conformations for especially the pYE moiety in solution resemble that in the bound state. In the calculated minimum energy conformation in solution isoleucine is bent towards the pY aromatic ring, the occurrence of such conformation is experimentally confirmed by NMR. The estimated values for S(conf) of the EE- and AA-peptide were similar, suggesting no predominant role of preorganization of the solution conformation due to electrostatic repulsion. Apparently the thermodynamics obey the same entropy-enthalpy compensation relationship, which also was found to hold for other peptides and peptidomimetics binding to p60(src) family SH2 domains. The implications of the results for drug design are discussed.

Ligands↗
PubMed2002

Generate: a program for 3-D structure generation and conformational analysis of peptides and peptidomimetics.

The program Generate, aimed at generating 3-D structures for peptides and peptidomimetics, is presented. The algorithm is based on a build-up procedure, using a library of conformations of amino acid residues. This library is built from conformational analysis of amino acids placed in a di- or tripeptide environment to mimic the surroundings of the amino acid in a true peptide, considering different positions of the residue in the peptide chain (peptidyl fragment, NH(+)(3)-terminus or COO(-)-terminus). Cis-trans isomerism in the amide bonds is taken into account by construction of rotamer libraries for different isomers. Water solvation is included through the GB/SA model. New amino acid residues can easily be added to the libraries, making it possible to generate conformations of peptidomimetics.

Amino Acid Sequence↗
PubMedDate not supplied

Fast calculation of quantum chemical molecular descriptors from the electronegativity equalization method.

The use of the Electronegativity Equalization Method (EEM) is presented for high performance calculation of molecular electrostatic descriptors, giving quite similar results to those obtained through Density Functional Theory (B3LYP/6-31G*) calculations. Molecular descriptors include atomic charges and different related descriptors as well as Fukui functions, hardness and softness.

Journal Article↗
PubMedDate not supplied

Quantum similarity superposition algorithm (QSSA): a consistent scheme for molecular alignment and molecular similarity based on quantum chemistry.

The use of the molecular quantum similarity overlap measure for molecular alignment is investigated. A new algorithm is presented, the quantum similarity superposition algorithm (QSSA), expressing the relative positions of two molecules in terms of mutual translation in three Cartesian directions and three Euler angles. The quantum similarity overlap is then used to optimize the mutual positions of the molecules. A comparison is made with TGSA, a topogeometrical approach, and the influence of differences on molecular clustering is discussed.

Aldosterone↗
PubMedDate not supplied

Quality of approximate electron densities and internal consistency of molecular alignment algorithms in molecular quantum similarity.

The calculation of molecular quantum similarity measures using the molecular electron density requires the electron density and molecular alignment between two molecules. To obtain meaningful quantum similarity matrices, the electron density should be calculated efficiently and accurately and the alignment should be internally consistent. The internal consistency of the alignment for a series of molecules is investigated through distance geometry concepts. The calculation of the quantum similarity matrix requires the calculation of a quadratic number of similarity integrals, and a scheme to obtain these efficiently is developed. Both the alignment procedure and the ASA method for approximate molecular electron densities are tested for a set of steroid molecules.

Journal Article↗
PubMedDate not supplied

Coulomb and overlap self-similarities: a comparative selectivity analysis of structure-function relationships for auxin-like molecules.

Auxins are defined mainly by a set of physiological actions, but the structure-effect relationship still is based on chemical intuition. Currently a well-defined auxin molecular structure is not available. The existence of different auxin binding proteins and mechanisms of auxin action, the wide diversity of the auxin molecules, and the pleiotropic effects of auxin imply a completely different mechanism as described for the animal hormone concept. Here, we present a computational approach dealing with semiempirical optimizations of the auxin molecules themselves, which represent a number of about 250 different chemical structures. Our approach uses molecular quantum similarity measures and additional quantum variables for the analysis of auxin-like molecules. The finding of similarities in molecules by focusing basically on their electron structure results in new insights in the relationship of the different auxin groups. Additional statistical analysis allows the identification of relationships between similarity groups and their biological activity, respectively. It is postulated that the auxin-like molecular recognition depends more on specific molecular assembling states than on a specific ring system or side chain.

Indoleacetic Acids↗