Les polyphénols sont abondamment trouvés dans de nombreux fruits, légumes, boissons etc. et ils possèdent de nombreux effets bénéfiques pour la santé. Les méthodes de calcul ont été utilisées dans le cadre de cette thèse pour rationaliser, décrire et prédire les propriétés physiques et chimiques des flavonolignanes et des pyranoanthocyanines pour la compréhension de leurs actions biologiques au niveau moléculaire. Tous les résultats des calculs théoriques ont été discutés par rapport aux données expérimentales. Les propriétés liées à l'activité antioxydante des flavonolignanes ont été étudiées par les méthodes de la théorie de la densité fonctionnelle (DFT). La dépendance au pH des propriétés d'absorption UV/Vis des flavonolignanes et des pyranoanthocyanines ont été évaluée par des méthodes DFT dépendante du temps (TD-), et les interactions non-covalentes ont été étudiées avec les méthodes de DFT incluant la correction de dispersion. Un bref aperçu est également donné sur l'interaction de ces composés avec des biomolécules. Le chapitre 6 présente des résultats non encore publiés de plusieurs systèmes non-covalents pigment: copigment. Cette partie des résultats constitue un bon point de départ pour la recherche du ‘meilleur copigment’. / Polyphenols are abundantly found in many fruit, vegetables, beverages, etc. and they possess many potential health benefits. Computational methods were thoroughly used through this thesis to rationalize, describe and predict physical chemical properties of flavonolignans and pyranoanthocyanins. Here, we aim at an understanding of polyphenol biological actions at a molecular level. All outcomes from the theoretical computations were discussed with respect to experimental data. The properties related to antioxidant activity of flavonolignans were investigated by density functional theory (DFT) methods. The pH dependence of ultraviolet/visible (UV/Vis) absorption properties of flavonolignans and pyranoanthocyanins were evaluated by time dependent (TD-) DFT methods, and noncovalent interactions were investigated within dispersion-corrected DFT methods. A short overview is also given on interaction of such compounds with biomolecules. Chapter 6 presents yet not published results of several noncovalent pigment: copigment systems. This part of the results serves as a good starting point to search for ‘the best copigment’.

L'astringence résulte de l'interaction des tanins, polyphénols abondants dans les végétaux, avec les protéines salivaires et plus particuliÈrement les protéines salivaires riches en proline (PRP), appartenant à la famille des protéines peu structurées. Les tanins participent aux mécanismes de défense des végétaux et présentent des effets antinutritionnels dus à leur capacitè à inhiber les enzymes digestives. La synthÈse de PRP salivaires constitue un mècanisme d'adaptation à la consommation d'aliments riches en tanins. Ce travail vise à caractèriser les complexes ètablis en solution entre les PRP et les tanins, par une approche basèe sur la spectromètrie de masse (MS). Pour cela, les protèines salivaires humaines IB5, PRP basique, et II-1, PRP glycosylèe, ont ètè produites par voie hètèrologue. AprÈs purification, les deux protèines ont ètè caractèrisèes par MS avec une source d'electronèbullisation (ESI-MS) et avec une source MALDI (Matrix-Assisted Laser Desorption/Ionisation). L'ètude des interactions par ESI-MS a confirmè la prèsence en solution de complexes non-covalents IB5tanin et permis de prèciser leurs stchiomètries. Des expèriences de compètition entre diffèrents tanins et de dissociation des complexes IB5tanin ont mis en èvidence l'influence des principales caractèristiques structurales des tanins sur cette interaction. L'ètude structurale des èdifices IB5tanin, par diffèrentes techniques de MS/MS (Collision Induced Dissociation, Electron Capture Dissociation et photodissociation) et par mobilitè ionique couplèe à la MS, a mis en èvidence la prèsence de plusieurs sites d'interaction sur IB5 ainsi que des changements conformationnels liès à l'interaction / Astringency is an important organoleptic property of plant-based food. It is attributed to interactions of tannins, which are polyphenolic compounds, with salivary proteins and especially proline rich proteins (PRPs), which belong to the group of intrinsically unstructured protein (IUP). Tannins play an important part in plant defence mechanisms. Indeed, they have an antinutritional effect as they inhibit digestive enzymes. Production of salivary PRP is thus an adaptation process to tannin-rich diets. The purpose of this work is to provide a closer look at PRPtannin supramolecular edifices in solution, using a mass spectrometry (MS) approach. The human salivary proteins IB5, a basic PRP, and II-1, a glycosylated PRP, have been produced by heterologous expression. After purification, both proteins have been characterized by MS using electrospray (ESI) and Matrix-Assisted Laser Desorption/Ionisation (MALDI) sources. The study of the interaction between IB5 and model tannins by ESI-MS confirmed the presence of IB5tannin non covalent complexes in solution and provided new information on their stoichiometries. Competitive interaction experiments between IB5 and two tannins, along with IB5tannin complexes dissociation studies revealed the impact of the main tannin chemical features on this interaction. Structural studies performed on IB5tanin edifices by Collision induced dissociation (CID), Electron Capture Dissociation (ECD) and photodissociation MS/MS experiments and by ion mobility coupled with MS showed the presence of several interaction sites on IB5 and conformational changes arising from the interaction.

The aim of this thesis is to investigate strength and origin of the stabilization for various types of noncovalent interactions. As this knowledge could lead to a deeper understand- ing and rationalization of the binding phenomena. Further, to participate on the de- velopment of new noncovalent data sets, which are nowadays inevitable in the process of parametrization and validation of new computational methods. In all the studies, different binding motifs of model complexes, which represent usually crystal structures, structures from unrelaxed scans or the local minima, were investi- gated. The calculations of the reference stabilization energies were carried out at ab initio level (e.g. CCSD(T)/CBS, QCISD(T)/CBS). Further, the accuracy of more ap- proximate methods (e.g. MP2.5, DFT-D or SQM methods) toward reference method, was tested. In order to obtain the nature of the stabilization the DFT-SAPT decompo- sition was frequently utilized. In the first part of the thesis, the importance and basic characteristics of different types of noncovalent interactions (e.g. halogen bond, hydrogen bond, π· · · π interaction etc.), are discussed. The second part provides the description of computational methods which were essential for our investigation. The third part of the thesis provides an overview for part...

Advances in computing capabilities have facilitated the application of quantum mechanical methods to increasingly larger and more complex chemical systems, including weakly interacting and biologically relevant species. One such ab initio-based composite methodology, the correlation consistent composite approach (ccCA), has been shown to be reliable for the prediction of enthalpies of formation and reaction energies of main group species in the gas phase to within 1 kcal mol-1, on average, of well-established experiment, without dependence on experimental parameterization or empirical corrections. In this collection of work, ccCA has been utilized to determine the proton affinities of deoxyribonucleosides within an ONIOM framework (ONIOM-ccCA) and to predict accurate enthalpies of formation for organophosphorus compounds. Despite the complexity of these systems, ccCA is shown to result in enthalpies of formation to within ~2 kcal mol-1 of experiment and predict reliable reaction energies for systems with little to no experimental data. New applications for the ccCA method have also been introduced, expanding the utility of ccCA to solvated systems and complexes with significant noncovalent interactions. By incorporating the SMD solvation model into the ccCA formulation, the Solv-ccCA method is able to predict the pKa values of nitrogen systems to within 0.7 pKa unit (less than 1.0 kcal mol-1), overall. A hydrogen bonding constant has also been developed for use with weakly interacting dimers and small cluster compounds, resulting in ccCA interaction energies for water clusters and dimers of the S66 set to within 1.0 kcal mol-1 of well-established theoretical values.

Supramolecular polymers represent a family of polymeric materials that are held together with dynamic, noncovalent interactions. In contrast to conventional functional polymers that usually have high melt-viscosity due to their covalent nature and chain entanglement, supramolecular polymers combine excellent physical properties with low melt-viscosity, allowing for less energy-intensive processability and recyclability. Dynamic bonding with multiple binding sites, such as multiple hydrogen bonding or multiple ionic bonding, exhibits much stronger binding strength compared to the counterparts containing only a single binding site, thereby allowing for enhanced mechanical integrity to the polymers and facilitate self-assembly. This dissertation focuses on the design of novel supramolecular polymers building from the doubly-charged or quadruple hydrogen bonding (QHB) scaffolds utilizing chain-growth polymerization or step-growth polymerization, as well as elucidate the structure-property-morphology relationships of the polymers. A 2-step nucleophilic substitution reaction afforded a series of 1,4-diazabicyclo[2.2.2]octane (DABCO)-based styrenic monomers with two pairs of charged groups. An optimized 2-step reversible-addition-fragmentation chain-transfer (RAFT) polymerization synthesized ABA triblock thermoplastic elastomers (TPEs) with a low Tg poly (n-butyl acrylate) central block and a high Tg external charged blocks. Strong ionic interactions between doubly-charged units drove molecular self-assembly to form densely packed, hierarchical microstructures, which contributed to a robust, crosslinked physical network that allows the polymer to retain thermomechanical integrity until degradation. High-resolution single-crystal X-ray diffraction (SCXRD) coupled with powder X-ray diffraction (PXRD) further disclosed a detailed 3-D structural information of molecular arrangement and ion distribution within the charged phase through comparing DABCO-salt monomer single-crystal structure and the corresponding homopolymer XRD pattern. It was found that the physical properties of the DABCO-salt copolymers not only relied on their charge content and architectures but also dependent on their electrostatically-bonded counterions. The size and structure of the counterion determined the strength of dipole-dipole interaction, which significantly impact on thermal property, (thermo)mechanical performance, water affinity, and microstructure. A cytosine-functionalized monomer, cytosine acrylate (CyA), allowed the synthesis of acrylic ABA triblock TPEs with pendant nucleobase moieties in the external blocks and a low Tg central polymer matrix through RAFT polymerization. Post-functionalization of cytosine (Cyt) bidentate hydrogen bonding sites with alkyl isocyanate, allowed the formation of ureido-cytosine (UCyt) groups in the external block that were readily dimerized through QHB interactions. The UCyt units in the external block enhanced mechanical strength and induced stronger phase-separation of the block copolymers compared to the corresponding Cyt-containing TPE analogs. Facile conventional free-radical polymerization using CyA and subsequent post-functionalization enabled accessibility to random copolymers containing pendant UCyt QHB moieties in the soft polymer matrix. The synergy of the flexible polymer matrix and the dynamic character of QHB groups contributed to the ultra-high elasticity of the polymer and rapid self-healing properties. QHB interactions enabled efficient mechanical recovery upon deformation by facilitating elastic chain retraction to regenerate the original physical network. Finally, one-pot step-growth polymerization through chain extending a novel bis-Cyt monomer and a commercially available polyether diamine using a di-isocyanate extender afforded segmented polyurea series for extrusion additive manufacturing. The molecular design of the polyureas featured soft segments containing flexible polyether chain and a relatively weak urea hydrogen bonding sites in the soft segment and rigid UCyt hydrogen bonding groups in the hard segment. The reversible characteristics of QHB enabled low viscosity at the processing temperature while providing mechanical integrity after processing and reinforced bonding between the interlayers, which contributed to the remarkable strength, elasticity, toughness, and interlayer adhesion of the printed parts. / Doctor of Philosophy / This dissertation focuses on designing supramolecular thermoplastic elastomers containing strong noncovalent interactions, i.e., quadruple hydrogen bonds or double ionic bonds. Inspired from noncovalent interactions in our mother nature, a series of bio-inspired monomers functionalized with nucleobase or ionic units were synthesized through scalable reactions with minimal purification steps. Polymerization of the functional monomers through step-growth or chain-growth polymerization techniques affords a variety of supramolecular thermoplastic elastomers with well-defined structures and architectures. These thermoplastic elastomers comprise soft and hard constituents; the former contains low glass transition polymer chains that provide elasticity while the latter contains strong noncovalent units to impart mechanical strength. Varying the soft/hard component ratios enables polymers with tunable physical properties to address different needs. Systematic characterizations of these supramolecular polymers revealed their distinct properties from the polymers containing the covalent or weak noncovalent interactions and facilitate molecular-level understanding of the polymers. Generally, incorporating strong noncovalent interactions increases the temperature for polymer segmental motion and extends thermomechanical plateau windows. Additionally, the strong association strength of those non-covalent interactions promotes microphase separation and self-assembly, contributing to a high degree of structural ordering of the polymers. Moreover, the dynamic characteristics of the noncovalent interactions offer the polymers with reversible properties, which not only enables melt-processability and recyclability of the polymer but also contributes to a series of smart properties, including self-healing, shape-memory, and recoverability. Thus, the molecular design using supramolecular chemistry provides promising avenues to developing functional materials with enhanced mechanical properties, processability, and stimuli-responsiveness for emerging applications.

L’any 2002 tres grups de recerca, entre ells el nostre grup, van demostrar teòricament que la interacció entre anions i anells aromàtics electrodeficients, anomenada interacció anió–, era favorable. Des de llavors s’ha dut a terme un intens estudi de la seva naturalesa física fins la total comprensió. Aquesta tesi es basa amb l’estudi de la interacció anió– des de tres punts de vista. Primerament, la investigació es basa en el disseny teòric de motius estructurals per donar lloc a un receptor on la interacció anió– siga molt favorable, per posteriorment avaluar la força de la interacció experimentalment en dissolució. A continuació, es va analitzar la interrelació entre un gran nombre de combinacions d’interaccions no covalents. A partir d’aquest estudi es defineixen nous conceptes i es proposen diferents formules per calcular efectes de cooperativitat. Finalment, hem anat un pas més enllà en l’estudi de la interacció analitzant: 1) l’impacte de la interacció anió– a sistemes biològics; 2) la influència de modificacions a l’anió sobre la naturalesa física de la interacció. / In 2002 three research groups, among them our research group, theoretically demonstrated that the interaction between anions and electron-deficient aromatic rings, named anion– interaction, was favourable. Since then, an intense study of its physical nature has been performed to understand it completely. This thesis is based on the study of the anion– interaction from three points of view. Firstly, theoretical design of binding units to build a receptor and to obtain the most favourable binding based on anion– interactions. The binding properties of these receptors have been experimentally assessed in solution. Secondly, we have studied the interplay between a great combination of noncovalent interactions. From this study, new concepts and formula to calculate cooperativity effects have been described. Finally, we have study one step further the anion– interaction analysing: 1) the impact of anion– interaction in biological systems; 2) how the modifications in the anion influence the physical nature of the interaction.