Daniel P. Vercauteren

Electronic properties of polypyrrole: An abinitio Hartree–Fock study

We present band structure calculations on neutral polypyrrole. The calculations are performed at the Hartree–Fock ab initio level with the use of a program specifically adapted for polymer applications. The density of states computed from the band structure compares very well with the UPS data on neutral polypyrrole.

A reversible monoamine oxidase inhibitor, toloxatone : spectrophotometric and molecular orbital studies of the interaction with flavin adenine dinucleotide (FAD)

Abstract Toloxatone is a monoamine oxidase A (MAO A ) inhibitor, marketed as antidepressant devoid of the undesirable side effects of first-generation irreversible monoamine oxidase inhibitors (MAOIs). Its advantages arise from the reversible, competitive and specific nature of its inhibition. The mechanism for irreversible inhibition of MAO A at the molecular level is known (suicide substrate). A physicochemical study was undertaken to establish the mechanism of reversible inhibition by Toloxatone. After determination of structural and electronic properties [6], experimental and theoretical approaches were used to explore the possibility of a physical association between the eutomer R -Toloxatone and flavin, a cofactor of MAO A . For this, 2 models of flavin were used. First, the existence of a charge-transfer complex between R -Toloxatone and riboflavin was demonstrated by electron absorption spectroscopy. Second, ab initio Hartree-Fock calculations of frontier orbitals and electrostatic potentials confirm the favourable overlap of complementary electronic zones of R -Toloxatone and SCH 3 -lumiflavin for a defined relative orientation.

A reversible monoamine oxidase inhibitor, toloxatone: Structural and electronic properties

Abstract Toloxatone is a reversible MAOA-inhibitor, marketed as antidepressant (Humoryl®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner.

Quantum mechanical approach to the chemisorption of molecular hydrogen on defect magnesium oxide surfaces

AbstractQuantum mechanical theoretical calculations have been performed on the linear atomic chain

A reversible monoamine oxidase inhibitor, Toloxatone: comparison of its physicochemical properties with those of other inhibitors including Brofaromine, Harmine, R40519 and Moclobemide

(MgOHV_{\ddot Mg} HOMg)^{2 + }

Correlation effects in molecular diffusion in zeolites at infinite dilution

in order to simulate the interaction of molecular hydrogen with the defects present at the surface of activated MgO. The total energy of the system, the relative energy of the various molecular orbitals, and the electronic charge distribution have been computed for various lattice parameters (dO-O = 4.0–4.8 Å) as a function of the H-H (or O-H) separation. A symmetrical motion of the hydrogen nuclei with respect to the central Mg2+ vacancy was assumed. It is shown that chemisorption of hydrogen on surface O−ions sites results in the formation of pseudo-hydroxyl groups. For a small lattice parameter (4.0 Å), no stable state of molecular hydrogen has been found while an increase in the lattice parameter results in a uniform increase of the calculated activation energy for the molecular hydrogen activation process. A mechanism is proposed which is not so different from that put forward for the hydrogen activation by transition metal complexes. Molecular hydrogen is found to act as an electron donor.

Interactive flexible molecular fitting program to be integrated into computer-aided molecular modelling systems

The interaction energy and the structure of water molecules either inside the Gramicidin A transmembrane channel or at its two extremities is examined with the use of iso-energy maps and Monte Carlo simulations. The shape of the channel as experienced by water is analyzed in detail. Variations in the hydration structure due to the presence of a Na+ ion placed at several positions along the channel are simulated, analyzed and discussed. Preliminary data on Li+ and K+ interacting with Gramicidin A and the system of water molecules are reported. The Gramicidin A atomic coordinates have been taken from Urrys recent papers.

Dynamics of sorbed molecules in zeolites

Summary Reversible, competitive and selective monoamine oxidase A inhibitors (MAO A Is) are an exciting new type of anti-depressants with a safe profile. The mechanism for reversible inhibition of MAO A at the molecular level is still unknown. The planar structure of most reversible MAO A Is and the well-defined acceptor power of flavin adenine dinucleotide (FAD), the cofactor of the enzyme, suggest that MAO A Is exert their inhibitory effect through charge-transfer interactions with the FAD. This hypothesis has been evaluated for Toloxatone 1 , the first reversible MAO A I marketed in France. In this work, we give evidence for the ability of other reversible MAO A Is, including Brofaromine 2 , Harmine 3 and R40519 4 to interact with the flavin cofactor in comparison with Moclobemide 5 , and we underline the physicochemical properties required for these interactions. First, the formation of a complex between each of the MAO A Is and riboflavin, a model of the flavin cofactor, is shown by electronic absorption spectroscopy. Essential electronic descriptors of MAO A Is, such as the molecular electrostatic potential and the topology of the frontier orbitals, are then calculated by the ab initio Hartree—Fock method and compared with those of previously studied Toloxatone. This confirms the electronic absorption spectroscopy results. Finally, the similarities between the different MAO A Is are underlined and an interaction model is discussed on the basis of a detailed analysis of the electronic descriptors of all the considered MAO A Is and the flavin nucleus.