Basicité des Amines et de Nicotines : Liaison Hydrogène et Protonation.

The most characteristic property of amines is their ability to behave as bases. We have then measured a type of basicity that has never been really studied at that time, their hydrogen bonding basicity. We have determined the thermodynamic parameters, ∆G, ∆H and ∆S, of the hydrogen bond complexation of 4-fluorophenol with about a hundred amines. We have also determined the spectroscopic scale of hydrogen bond basicity, ∆ν(OH) and showed that each of the three scales makes its contribution to the knowledge of the basicity of amines. The study of different empirical (substituent effects) and theoretical (electrostatic potential, electronic energy variation by complexation) parameters of hydrogen bonding basicity is investigated. The lipophilicity of about 100 nitrogen bases is successfully predicted with only two structural parameters : the molar volume and the Gibbs energy of hydrogen bonding. We show moreover that the hydrogen bond basicity scale is very different of the scales of Brönsted basicity pKa in aqueous solutions or GB in the gas phase. In a second part, we study the ability of nicotine and nornicotine to form hydrogen bonds and to protonate in the gas phase with the aim of analysing the potential interactions between these molecules and their receptors. Indeed, nicotine has two competitive basic sites : an amino nitrogen and a pyridine nitrogen. We show that, for nicotine and nornicotine, the amino nitrogen is a secondary hydrogen bond acceptor site which is at the origin of the lipophilicity of these bases. In gas phase, the protonation site of nornicotine is the pyridine nitrogen, favoured by an intramolecular hydrogen bond CHLN. Nevertheless, the proton basicities of the two nicotine nitrogens seem to be very similar.La principale propriété des amines est leur basicité. Nous avons donc mesuré un type de basicité des amines non encore réellement étudié à ce jour, leur basicité de liaison H. Nous l'avons fait par la détermination des paramètres thermodynamiques, ∆G, ∆H et ∆S, de la réaction de formation de liaison H entre le 4-fluorophénol, et une centaine d'amines. Nous avons également déterminé l'échelle spectroscopique de basicité de liaison H, ∆ν(OH) et montrons que chacune des échelles ∆G, ∆H et ∆ν(OH) apporte sa contribution à la connaissance de la basicité des amines. L'étude de différents descripteurs empiriques (effets de substituants) et théoriques (potentiel électrostatique, variation d'énergie électronique par complexation) de la basicité de liaison H est réalisée. La lipophilie d'environ 150 bases azotées est modélisée avec succès à partir de seulement deux paramètres structuraux : le volume molaire et l'énergie de Gibbs de liaison H. Nous montrons également que l'échelle de basicité de liaison H est différente des échelles de basicité de Brönsted pKa en solution aqueuse ou GB en phase gazeuse. Dans ce contexte nous avons étudié l'aptitude de la nicotine et la nornicotine à former des liaisons H et à se protoner en phase gazeuse. En effet la nicotine possède une riche activité biologique et son pharmacophore est constitué d'un azote amino protoné et d'un azote pyridinique accepteur de liaison H. Nous montrons que l'azote sp3 est un second site accepteur de liaison H, pour la nicotine et la nornicotine, expliquant la lipophilie de ces bases. Le site de protonation de la nornicotine en phase gazeuse est l'azote sp2, très favorisé par une liaison intramoléculaire CHLN. Par contre les basicités protoniques des deux azotes de la nicotine semblent très peu différentes

Conformations and Binding Properties of Thiametoxam and Clothianidin Neonicotinoid Insecticides to Nicotinic Acetylcholine Receptors: The Contribution of sigma-Hole Interactions

International audienceThe structural features and molecular-interaction properties of thiamethoxam (THA) and clothianidin (CLO) - two neonicotinoids - have been investigated through a combined approach based on a wide range of molecular modeling methods and X-ray-structure observations. Despite their close chemical structures, significant differences are emphasized by QM (DFT), docking, molecular dynamics, and QM/QM ` calculations. Thus, for the first time, their propensity to interact through chalcogen-bond interactions is highlighted. The influence of the surroundings on this behavior is pointed out: in CLO, an intramolecular S center dot center dot center dot N chalcogen bond is shown to stabilize the structure in the solid state whereas the interaction leads to the preferred conformations in the isolated and continuum solvent models for both compounds. Interestingly, this interaction potential appears to be used for their binding to Ac-AChBP through intermolecular S center dot center dot center dot O chalcogen bonds with the hydroxyl group of Tyr195. The use of a suitable level of theory to describe properly these interactions is underlined, the classical methods being unsuited to highlight these interactions. The contribution of halogen bonding through the chlorine atom of the chlorothiazole ring in the binding of the two compounds is also underlined, both in the solid state and in the Ac-AChBP surroundings. However, the accommodation of the two insecticides in the binding site leads to the fact that a halogen-bond contribution is pointed out only for CLO

Hydrogen-Bond Acidity of OH Groups in Various Molecular Environments (Phenols, Alcohols, Steroid Derivatives, and Amino Acids Structures): Experimental Measurements and Density Functional Theory Calculations

The hydrogen-bond (H-bond) donating strengths of a series of 36 hydroxylic H-bond donors (HBDs) with N-methylpyrrolidinone have been measured in CCl4 solution by FTIR spectrometry. These data allow the definition of a H-bond acidity scale named pK(AHY) covering almost three pK units, corresponding to 16 kJ mol(-1). These results are supplemented by equilibrium constants determined in CH2Cl2 for one-third of the data set to study compounds showing a poor solubility in CCl4. A systematic comparison of these experimental results with theoretical data computed in the gas phase using DFT (density functional theory) calculations has also been carried out. Quantum electrostatic parameters appear to accurately describe the H-bond acidity of the hydroxyl group, whereas partial atomic charges according to the Merz-Singh-Kollman and CHelpG schemes are not suitable for this purpose. A substantial decrease of the H-bond acidity of the OH group is pointed out when the hydroxyl moiety is involved in intramolecular H-bond interactions. In such situations, the interactions are further characterized through AIM and NBO analyses, which respectively allow localizing the corresponding bond critical point and the quantification of a significant charge transfer from the available lone pair to the sigma(OH)* antibonding orbital. Eventually, the H-bond ability of the hydroxyl groups of steroid derivatives and of lateral chains of amino acids are evaluated on the basis of experimental and/or theoretical data

Towards a stronger halogen bond involving At — Investigation of halogen-bonded adducts of AtI and Bu3PO

International audienc

New insights on the molecular features and electrophysiological properties of dinotefuran, imidacloprid and acetamiprid neonicotinoid insecticides

Structural features and hydrogen-bond interactions of dinotefuran (DIN), imidacoloprid (IMI) and ace-tamiprid (ACE) have been investigated experimentally through analyses of new crystal structures and observations in structural databases, as well as by Density Functional Theory quantum chemical calculations. Several conformations are observed experimentally in the solid state, highlighting the large flexibility of these compounds. This feature is confirmed by the theoretical calculations in the gas phase, the numerous and different energetic minima of the three neonicotinoids being located within a 10 kJ/mol range. Comparisons of the observed and simulated data sheds light on the hydrogen-bond (HB) strength of the functional group at the tip of the electronegative fragment of each pharmacophore (NO2 for DIN and IMI and C N for ACE). This effect originates in the `push-pull' nature of these fragments and the related extensive electron delocalization. Molecular electrostatic potential calculations provide a ranking of the two fragments of the three neonicotinoid in terms of HB strength. Thus, the NO2 group of DIN is the strongest HB acceptor of the electronegative fragment, closely followed by the cyano group of ACE. These two groups are significantly more potent than the NO2 group of IMI. With respect to the other fragments of the three neonicotinoids, the nitrogen atom of the pyridine of IMI and ACE are stronger HB acceptors than the oxygen atom of the furanyl moiety of DIN. Finally, compared to electrophysiological studies obtained from cockroach synaptic and extrasynaptic receptors, DIN appears more effective than IMI and ACE because it strongly increases dose-dependently the ganglionic depolarisation and the currents amplitudes. These data suggest that DIN, IMI and ACE belong to two subgroups which act differently as agonists of insect nicotinic receptors. (C) 2011 Elsevier Ltd. All rights reserved

Sulfoximine derivative, sulfoxaflor, activates imidacloprid-sensitive nicotinic acetylcholine receptors on insect neurosecretory cells

256th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nanoscience, Nanotechnology and Beyond, Boston, MA, AUG 19-23, 201