Une famille de pinces moléculaires commutables par coordination métallique basées sur une architecture modulaire de type bis(M-salphen) terpyridine (salphen = N,N’-disalicylidene-o-phenylenediamine) a été synthétisée dans le but de moduler, par un effet mécanique, des propriétés physiques ou chimiques à l’échelle moléculaire. Deux pinces fonctionnalisées par des complexes phosphorescents de platine(II) ont été synthétisées par une approche modulaire. Un mouvement réversible de fermeture et d’ouverture par coordination / décoordination a été obtenu ainsi qu’une extinction de la luminescence via un contrôle allostérique de la reconnaissance de Hg2+. Une pince comportant des complexes paramagnétiques de cuivre (II) a permis l’observation par RPE et SQUID d’une commutation réversible de l’interaction d’échange à travers l’espace entre les deux centres métalliques. Du manganèse(III) a également été utilisé afin de permettre la commutation de l’interaction d’échange via un ligand pontant cyanure grâce à un contrôle allostérique de l’intercalation. De manière similaire, la synthèse d’une pince moléculaire incorporant des unités molécule aimant a été mise au point. D’autre part les propriétés rédox d’une pince à base de nickel(II) ont aussi pu être contrôlées par le mouvement et l’intercalation de pyrazine dans la forme oxydée nickel(III). Finalement, la synthèse d’une pince catalytique a été mise au point, ouvrant la voie à des catalyseurs commutables biomimétiques fonctionnant par effet allostérique. / A family of switchable molecular tweezers based on a bis(M-salphen) terpyridine (salphen = N,N’-disalicylidene-o-phenylenediamine) structure has been developed to study the influence of a mechanical motion on physical properties at the molecular level. Two tweezers functionalized by phosphorescent platinum (II) complexes were synthesized using a modular approach. The reversible mechanical motion by coordination / decoordination of a first metal cation allowed reversible quenching of the luminescence thanks to mercury (II) intercalation with allosteric control. Similar tweezers bearing paramagnetic copper (II) permitted to reversibly switch through-space exchange interactions between the two metallic centers according to EPR and SQUID measurements. manganese (III) was also used in order to switch the exchange interaction through a cyanide bridging ligand whose intercalation can be controlled by allosteric effect. With a similar strategy, the synthetic route towards tweezers showing single-molecule-magnet behavior has beendeveloped. The redox property of nickel(II) based tweezers was also controlled by the mechanical motion and the intercalation of pyrazine in the oxidized nickel (III) closed form. Finally, the synthesis of catalytic tweezers was developed, opening the way to switchable biomimetic catalysts operating with allosteric control.

<p>Understanding and predicting chemical phenomena is the main goal of computational chemistry. In this thesis I present my work on applying computational approaches to study chemical processes in biological and supramolecular systems.</p> <p>pH-responsive molecular tweezers have been proposed as an approach for targeting drug-delivery to tumors, which tend to have a lower pH than normal cells. In chapter 2 I present a computational study I performed on a pH-responsive molecular tweezer using <em>ab initio</em> quantum chemistry in the gas phase and molecular dynamics simulations in solution. The binding free energy in solution was calculated using Steered Molecular Dynamics. We observe, in atomistic detail, the pH-induced conformational switch of the tweezer and the resulting release of the drug molecule. Even when the tweezer opens, the drug molecule remains near a hydrophobic arm of the molecular tweezer. Drug release cannot occur, it seems, unless the tweezer is a hydrophobic environment with low pH.</p> <p>The protonation state of amino acid residues in proteins depends on their respective pK_a values. Computational methods are particularly important for estimating the pK_a values of buried and active site residues, where experimental data is scarce. In chapter 3 I used the cluster model approach to predict the pK_a of some challenging protein residues and for which methods based on the numerical solution of the Poisson-Boltzmann equation and empirical approaches fail. The ionizable residue and its close environment were treated quantum mechanically, while the rest of the protein was replaced by a uniform dielectric continuum. The approach was found to overestimate the electrostatic interaction leading to predicting lower pK_a values.</p> / Master of Science (MSc)