Alexandre Hocquet

The peculiar role of cytosine in nucleoside conformational behaviour: Hydrogen bond donor capacity of nucleic bases

According to theoretical calculations, both 2′-deoxycytidine and cytidine show a different energetical behaviour as compared to the other nucleosides. A C–H···O intramolecular hydrogen bond is suspected to greatly influence the conformational behaviour of the nucleosides. The donor atom is the H6 (H8) atom of the pyrimidic (puric) nucleic base and the acceptor atom is the O5′ atom of the sugar. In the present work, we assess the hydrogen bond donor capacity of the H6/H8 hydrogen atom according to the base, by calculating deprotonation energies and electrostatic potentials. This allows us to state precisely that the peculiar behaviour of deoxycytidine expresses itself in the South conformation, and that cytidine does not behave like deoxycytidine.

Influence of the gelator structure and solvent on the organisation and chirality of self-assembling fibrillar networks

Chromophoric probes of naphthalimide moieties enable evaluation of their assembling behaviour photophysically through fluorescence spectroscopy and microscopy, and circular dichroism. These experiments highlight the influence of the nature of the chemical substitution of the organogelator. Very interesting results were also obtained by performing CD experiments showing that the nature of the solvent should modify the chirality of self-assembled aggregates. Highly oriented network structures were observed in the gel state and disappeared in isotropic solution. Microfibrous self-aggregation of organogels is in situ observed via fluorescence and SHG imaging and confirmed by transmission electron microscopic analysis of the dried sample.

Interaction of sodium and potassium ions with sandwiched cytosine-, guanine-, thymine-, and uracil-base tetrads.

Nucleic acid tetraplexes and lipophilic self‐assembling G‐quadruplexes contain stacked base tetrads with intercalated metal ions as basic building blocks. Thus far, quantum‐chemical studies have been used to explore the geometric and energetic properties of base tetrads with and without metal ions. Recently, for the first time, work on a sandwiched G‐tetrad complex has been studied. We report here results of a systematic B3LYP density functional study on sandwiched G‐, C‐, U‐, and T‐tetrads with Na+ and K+ at different symmetries that substantially extend the recent work. The results include detailed information on total energies as well as on metal ion tetrad and base–base interaction energies. The geometrical parameters of the sandwiched metal ion complexes are compared to both experimental structures and to calculated geometries of complexes of single tetrads with metal ions. A microsolvation model explains the ion selectivity preference of K+ over Na+ in a qualitative sense.

Guanine tetrads interacting with metal ions. An AIM topological analysis of the electronic density

The interaction of guanine tetrads with various alkaline, alkaline earth and transition metal ions has been studied by means of an AIM topological analysis of the electronic density based on density functional calculations. The interaction between metal ion and ligand has been characterized in terms of the Laplacian of the electronic density, the Hamiltonian kinetic energy density and the Lagrangian kinetic energy density. The influence of the metal ion–ligand interaction on tetrad hydrogen bonding is also discussed.

Are guanine tetrads stabilised by bifurcated hydrogen bonds? An AIM topological analysis of the electronic density

Following a previous publication (M. Meyer, M. Brandl and J Suhnel, J. Phys. Chem. A, 2001, 105, 8223–8225) on quantum mechanical calculations of guanine tetrads where the issue of the difference between bifurcated and Hoogsteen conformations was addressed geometrically and energetically, we tackle the problem from the Atoms in Molecules (AIM) point of view of the topological analysis of the electronic density. We provide electronic argumentation to discuss the bifurcated or Hoogsteen issue, from the analysis of density and laplacian at the bond critical point criteria, and from the integration of atomic properties. The Hoogsteen hydrogen bonding network appears to be stronger than the bifurcated one, and benefits more from cooperativity.

Stereodynamics of nitrogen chiral centers in aza-β3-cyclodipeptides.

The present work is devoted to the synthesis, conformational analysis, and stereodynamic study of aza-β(3)-cyclodipeptides. This pseudopeptidic ring shows E/Z hydrazide bond isomerism, eight-membered ring conformation, and chirotopic nitrogen atoms, all of which are elements that are prone to modulate the ring shape. The (E,E) twist boat conformation observed in the solid state by X-ray diffraction is also the ground conformation in solution, and emerges as the lowest in energy when using quantum chemical calculations. The relative configuration associated with ring chirality and with the two nitrogen chiral centers is governed by steric crowding and adopts the (P)S(N) S(N)/(M)R(N)R(N) combination which projects side chains in equatorial position. The nitrogen pyramidal inversion (NPI) at the two chiral centers is correlated with the ring reversal. The process is significantly hindered as was shown by VT-NMR experiments run in C2D2Cl4, which did not make it possible to determine the barrier to inversion. Finally, these findings make it conceivable to resolve enantiomers of aza-β(3)-cyclodipeptides by modulating the backbone decoration appropriately.

Mailing list archives as useful primary sources for historians: looking for flame wars

ABSTRACT This paper aims to show the potential of mailing list archives as primary sources for studying recent history of science. In order to focus on the debates regarding software within the computational chemistry community in the 1990s, the corpus we rely on consists in a scholarly mailing list, a typical corpus from its time, conceived, constructed and maintained by a community. The threaded conversations of the list also constitute a unique rhetorical form in its organisation which is technically bound to the Internet-based media of that time. We first present the issues at stake within our research topic and show how relevant is such a corpus to address them. We then discuss the “ethnographic” characteristics and the structure of the corpus. Its most interesting parts are the “flame wars”, that is outbursts of heated, short and dense debates, in an ocean of evenly distributed polite messages. We unveil how the relevant flame wars are located and extracted by producing a graphical representation of the number of messages per day over time. Once flame wars are isolated, the messages exchanged by practitioners are studied precisely to comprehend the argumentative structure of the debates and the different viewpoints of actors.

ALCHEMY 2000 VERSION 1.00 FOR WINDOWS : A REVIEW

Introduction. Developing tools for the next millenium. The new version of the Alchemy Tripos program is being called 2000. Like its older brother, Alchemy III, Alchemy 2000 is a molecular editor that offers some computational capabilities. The step into XXIst century is characterized by new graphics possibilities, openings to comprehensive file formats, and use of Windows 95 features. Thus, Tripos is investing again in “general audience” software, this kind of software that may be defined as cheap, working on a personal computer and with an easy-to-use interface. This review is intended to explore the capabilities of Alchemy 2000. It will try to be as objective as possible, but the opinion of the author may be influenced by his personal needs1 in this software and previous relations with Hyperchem, 2 and Spartan, 3 even though it should be quite clear that the goals of Alchemy 2000 are rather different from those softwares. System Requirements.The minimum hardware configuration as advised by Tripos 4 is a 486 processor, 8 Mb of RAM (16 Mb recommended), a hard disk with at least 40 Mb of free space, VGA graphics capabilities (800 × 600 pixels recommended), and a mouse. The system must run MS-DOS version 6.00 or higher and Windows version 3.11 or 95. As Alchemy 2000 relies on high definition graphics, the higher the performance of the computer graphics, the better. This study has been performed on a PC compatible with a Pentium processor (120 MHz) and 16 Mb of RAM, SVGA graphics, and 256 Kb of VRAM, running under Windows 95. Installation, Help, and Documentation. The installation is as straightforward as any Windows program. A local code, depending on the actual computer it is run with, must be provided by the distributor the first time the program is launched. The Alchemy 2000 program is Windows 95 compatible, although it will automatically reduce more-thaneight-letters-long filenames, like Windows version 3 software does. Alchemy 2000 is a multiwindow software and is customizable. The Help menu can provide useful information using the index command. This is appreciated, because the documentation manuals are not very thick and contain no index. The first manual, called Getting Started, presents an overview of the Alchemy 2000 capabilities and functions as a tutorial. It contains 18 chapters: Introduction (8 pages), The Desktop (9 pages), Opening and Closing Files (9 pages), Movement of Molecules (6 pages), Selection Tools (10 pages), Displaying Small Molecules (12 pages), Displaying Proteins (12 pages), Multiwindow Environments (7 pages), Building Small Molecules (27 pages), Building a Protein (12 pages), Small Molecule Energy Minimization (12 pages), Semiempirical Methods (8 pages), Batchmode (11 pages), RMS Fit (3 pages), Determining Bond Lengths and Angles (8 pages), The Presentation Pane (15 pages), Preferences (6 pages), and Auxiliary Programs (4 pages). The second manual, called Technical Reference Manual, presents the functionalities of Alchemy 2000 (10 chapters: Introduction (2 pages), The Desktop (12 pages), Working with Small Molecules (8 pages), Working with Proteins (6 pages), Molecular Dimensions and Properties (4 pages), Basics of Molecular Calculations (9 pages), Batchmode and the Log (4 pages), The Presentation Pane (6 pages), Files Types (4 pages), and Customizing Alchemy 2000 (7 pages)) and details each menu command (15 chapters). Some commands are not available in version 1.00 (for example, the Set Bond length, Bond Angle, Dihedral commands, or the Charge menu in the 2D sketcher), but an upgrade will be provided soon free of charge. The manuals are especially brief when describing scientific techniques, such as molecular mechanics or semiempirical methods. Furthermore, Tripos provides 60 days of support free of charge.