Upper Bounds for Regularized Determinants

We conjecture that the zeta-regularized determinant of the Laplace operator with coefficients in a holomorphic vector bundle on a compact K?hler manifold remains bounded when the metric on the bundle varies. This conjecture is shown to be true for certain classes of line bundles on Riemann surfaces. Received: 7 July 1997 / Accepted: 20 April 1998     

Interaction of nucleosides with antitumoural agents : 9-hydroxy-N-2-methylellipticinium acetate and 9-hydroxy-N-2-methylolivacinium acetate

Reaction of 9-hydroxypyrido[4,3-b] carbazole derivatives under oxidative conditions (biochemical : HRP/H₂O₂, chemical : Cu₂Cl₂/Pyridine/O₂) has been found to furnish regio-and stereo-selectively a ketalic linkage at the 10-position of this type of compound. Detailed structure elucidation of the products has been given. The regio- and stereo-specificity of the reaction has been demonstrated to be due to π-π stacking between the ribonucleosidic base and the 9-hydroxypyridocarbazole nucleus. Acid Catalysed isomerisation of $\text{11}$ to $\text{29}$ has also been studied in detail. In the light of these results, it is proposed that besides the “classical” intercalation into DNA, this type of compound can also react with RNA. This reactivity could explain, at least partially, the pharmacological (antitumour) activity of these compounds and should lead to a promising field of research in molecular biology.     

Décomposition thermique du monoxide de carbone sur une surface de molybdène: Formation de couches superficielles de carbone et de carbure

We have investigated the decomposition of carbon monoxide on polycrystalline and (001), (110) monocrystalline molybdenum surfaces. This study was performed by massspectrometry, for thermal desorption studies, Auger electron spectrometry (AES), low energy electron diffraction (LEED) and photoelectron spectroscopy (ESCA). By heating the clean Mo surface in CO or by heating the Mo surface covered with CO, the dissociation of chemisorbed CO leads to a build-up of carbon layer which inhibits the subsequent adsorption. Two distinct types of fine structure are associated with the KLL line of carbon Auger spectra. If the Mo surface is heated at a temperature between 300 and 1500 K, the Auger peak is characteristic of a “graphite layer”. If the Mo surface is heated at a temperature up to 2000 K, the Auger peak is characteristic of a “carbure” layer. This “carbure layer” give rise to a surstructure which agrees with a Mo₂C surface layer and was also investigated by ESCA. Chemical shifts of (1s) C and (3d) Mo photoemission bands were observed and attributed to the bounding between Mo and C atoms in the Mo₂C layer.     

Analytic torsion and holomorphic determinant bundles I. Bott-Chern forms and analytic torsion

We attach secondary invariants to any acyclic complex of holomorphic Hermitian vector bundles on a complex manifold. These were first introduced by Bott and Chern [Bot C]. Our new definition uses Quillen's superconnections. We also give an axiomatic characterization of these classes. These results will be used in [BGS2] and [BGS3] to study the determinant of the cohomology of a holomorphic vector bundle.     

Structural model of CO dissociation on Pd particles

In order to modelize the CO dissociation observed on palladium particles, by means of Static Secondary Ion Mass Spectrometry, theoretical investigations were performed on small Pd clusters by using a local approximation of the density functional theory. Several types of defects were studied concerning their ability to dissociate the CO molecule.     

Experimental/theoretical electrostatic properties of a styrylquinoline-type HIV-1 integrase inhibitor and its progenitors

We have established that polyhydroxylated styrylquinolines are potent inhibitors of HIV-1 integrase (IN). Among them, we have identified (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinolinecarboxylic acid (1) as a promising lead. Previous molecular dynamics simulations and docking procedures have shown that the inhibitory activity involves one or two metal cations (Mg2+), which are present in the vicinity of the active center of the enzyme. However, such methods are generally based on a force-field approach and still remain not as reliable as ab initio calculations with extended basis sets on the whole system. To go further in this area, the aim of the present study was to evaluate the predictive ability of the electron density and electrostatic properties in the structure-activity relationships of this class of HIV-1 antiviral drugs. The electron properties of the two chemical progenitors of 1 were derived from both high-resolution X-ray diffraction experiments and ab initio calculations. The twinning phenomenon and solvent disorder were observed during the crystal structure determination of 1. Molecule 1 exhibits a planar s-trans conformation, and a zwitterionic form in the crystalline state is obtained. This geometry was used for ab initio calculations, which were performed to characterize the electronic properties of 1. The electron densities, electrostatic potentials, and atomic charges of 1 and its progenitors are here compared and analyzed. The experimental and theoretical deformation density bond peaks are very comparable for the two progenitors. However, the experimental electrostatic potential is strongly affected by the crystal field and cannot straightforwardly be used as a predictive index. The weak difference in the theoretical electron densities between 1 and its progenitors reveals that each component of 1 conserves its intrinsic properties, an assumption reinforced by a 13C NMR study. This is also shown through an excellent correlation of the atomic charges for the common fragments. The electrostatic potential minima in zwitterionic and nonzwitterionic forms of 1 are discussed in relation with the localization of possible metal chelation sites.     

Scaffold hopping using clique detection applied to reduced graphs

Similarity-based methods for virtual screening are widely used. However, conventional searching using 2D chemical fingerprints or 2D graphs may retrieve only compounds which are structurally very similar to the original target molecule. Of particular current interest then is scaffold hopping, that is, the ability to identify molecules that belong to different chemical series but which could form the same interactions with a receptor. Reduced graphs provide summary representations of chemical structures and, therefore, offer the potential to retrieve compounds that are similar in terms of their gross features rather than at the atom-bond level. Using only a fingerprint representation of such graphs, we have previously shown that actives retrieved were more diverse than those found using Daylight fingerprints. Maximum common substructures give an intuitively reasonable view of the similarity between two molecules. However, their calculation using graph-matching techniques is too time-consuming for use in practical similarity searching in larger data sets. In this work, we exploit the low cardinality of the reduced graph in graph-based similarity searching. We reinterpret the reduced graph as a fully connected graph using the bond-distance information of the original graph. We describe searches, using both the maximum common induced subgraph and maximum common edge subgraph formulations, on the fully connected reduced graphs and compare the results with those obtained using both conventional chemical and reduced graph fingerprints. We show that graph matching using fully connected reduced graphs is an effective retrieval method and that the actives retrieved are likely to be topologically different from those retrieved using conventional 2D methods.     

Transferable specific scaling factors for interpretation of infrared spectra of biomolecules from density functional theory

A set of transferable local scaling factors is established for assignment of infrared spectra of molecular systems of biological interest experimentally recorded under gas-phase conditions. Each scaling factor is specific for an experimentally observable vibrational mode chosen among those bringing significant structural information. Those factors are provided for harmonic calculations at the DFT B3LYP and DFT B3PW91 levels respectively with 7 and 2 different basis sets. The used training set of neutral molecules comprises nucleobases, aminoacids, peptides, sugars, and neurotransmitters. The proposed specific scaling factors usable for unambiguous conformer assignments lead to typical prediction errors ca. 10 cm(-1) for free and moderately hydrogen-bonded group frequencies with red-shifts up to 200 cm(-1).