Yes / The syntheses of three series of complexes designed with self-complementary motifs for formation of halogen bonds between an iodotetrafluorophenyl ligand and a halide ligand at square-planar nickel are reported, allowing structural comparisons of halogen bonding between all four halides C6F4I⋯X–Ni (X = F, Cl, Br, I). In the series trans-[NiX(2,3,5,6-C6F4I)(PEt3)2] 1pX and trans-[NiX(2,3,4,5-C6F4I)(PEt3)2] (X = F, Cl, Br, I) 1oX, the iodine substituent on the benzene ring was positioned para and ortho to the metal, respectively. The phosphine substituents were varied in the series, trans-[NiX(2,3,5,6-C6F4I)(PEt2Ph)2] (X = F, I) 2pX. Crystal structures were obtained for the complete series 1pX, and for 1oF, 1oCl, 1oI and 2pI. All these complexes exhibited halogen bonds in the solid state, of which 1pF exhibited unique characteristics with a linear chain, the shortest halogen bond d(C6F4I⋯F–Ni) = 2.655(5) Å and the greatest reduction in halogen bond distance (I⋯F) compared to the sum of the Bondi van der Waals radii, 23%. The remaining complexes form zig-zag chains of halogen bonds with distances also reduced with respect to the sum of the van der Waals radii. The magnitude of the reductions follow the pattern F > Cl ∼ Br > I, 1pX > 1oX, consistent with the halogen bond strength following the same order. The variation in the I⋯X–Ni angles is consistent with the anisotropic charge distribution of the halide ligand. The temperature dependence of the X-ray structure of 1pF revealed a reduction in halogen bond distance of 0.055(7) Å on cooling from 240 to 111 K. Comparison of three polymorphs of 1oI shows that the halogen bond geometry may be altered significantly by the crystalline environment. The effect of the halogen bond on the 19F NMR chemical shift in the solid state is demonstrated by comparison of the magic-angle spinning NMR spectra of 1pF and 1oF with that of a complex incapable of halogen bond formation, trans-[NiF(C6F5)(PEt3)2] 3F. Halogen bonding causes deshielding of δiso in the component of the tensor perpendicular to the nickel coordination plane. The results demonstrate the potential of fluoride ligands for formation of halogen bonds in supramolecular structures. / We acknowledge an Overseas Research Scholarship from the University of York to VT. We also acknowledge support from EPSRC (grants EP/J012955/1 and EP/ J012998/1).

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / A family of bis-pyridine based pharmaceutical active ingredients were synthesized and co-crystallized with four iodoperfluoroalkanes. Thirteen new crystal structures that are driven by I‧‧‧N(py) halogen bonds, are presented and compared with that of their hydrogen-bonded analogues. Halogen bonded co-crystals exhibit two different structural arrangements, as opposed to layered architectures observed in hydrogen bonded co-crystals. In order to explore the effect of aromatic stacking interactions on hydrogen and halogen bond driven co-crystallization process, we utilized a series of aromatic hydrogen and halogen bond donors in combination with bis-pyridine based pharmaceutical active ingredients. Aromatic stacking between the donor and the acceptor were limited, due to the lack of complementarity between the donor and the acceptor in terms of size, shape and geometry. In that case, homomeric interactions between the single components were translated into the structure of the binary co-crystals. According to our charge calculations, similarly activated hydrogen and iodine atoms possess similar electrostatics. Therefore, we wanted to investigate the interchangeability of hydrogen bonds and halogen bonds by utilizing 2-aminopyrimidine as the backbone for C(sp)-H and C(sp)-I functionalities which makes self-complementary ribbons via NH‧‧‧N synthons. Our results show that the ethynyl proton is capable of acting as a synthon mimic of ethynyl iodine by interchangeable C(sp)-H‧‧‧N hydrogen bonds and C(sp)-I‧‧‧N halogen bonds. We exploited the halogen bonding donor capability of iodo, bromo and chloro ethynyl functionalities towards a series of halide ions. Based on the grinding experiments these donors showed 90%, 70% and 50% success rates towards halides. Among the halides, chlorides exhibited the highest red shift compared to bromides and iodides. We synthesized a series of cavitands functionalized with hydrogen bond donor and acceptor groups and studied their binding preferences towards a series of active ingredients. We have shown that suitably functionalized cavitands can act as carriers of active ingredients and especially, selective binding of aspirin is demonstrated using a two-point binding mode.

Ces travaux de thèse ont pour but l’étude théorique et la caractérisation d’interactions non-covalentes par des méthodes QCT (Quantum Chemical Topology), qui sont des outils interprétatifs de chimie quantique. Plusieurs interactions furent étudiées du point de vue de la densité électronique (calculs DFT), notamment des interactions intramoléculaires entre atomes halogènes ainsi que des liaisons halogène inter- et intramoléculaires. L’analyse topologique QTAIM complétée par la décomposition énergétique IQA (Interacting Quantum Atoms) nous a permis de dévoiler la nature physique des interactions étudiées, i.e. la part d’interaction électrostatique et la part d’échange (covalence). Il a été montré que l’échange tient un rôle majeur dans la stabilisation de telles interactions et permet de rationnaliser les différentes topologies observées en terme de compétition entre canaux d’échange primaires et secondaires. Aussi, la formation et la rupture d’une liaison hydrogène au cours de transferts de protons a été étudiée grâce à la décomposition de grandeurs globales (de DFTConceptuelle) en contributions monoatomiques ; le schéma de décomposition proposé se base sur la partition QTAIM et la décomposition énergétique IQA. Cette approche permet de suivre l’évolution, le long d’un chemin réactionnel, de la contribution de chaque atome à la réactivité du système. Une nouvelle façon de caractériser les barrières d’énergie potentielle et les états de transition a ainsi été proposée. / This work aims to theoretically investigate and characterize non-covalent interactions by means of Quantum Chemical Topology (QCT) methods, which are quantum chemistry interpretative tools. Several interactions were studied from the point of view of the electron density (DFT calculations), including intramolecular interactions between halogen atoms as well as inter- and intramolecular halogen bonds. The QTAIM topological analysis complemented by the Interacting Quantum Atoms (IQA) energy decomposition revealed the physical nature of those interactions, i. e. the part of electrostatics and the part of exchange (covalency). It has been shown that exchange plays a significant role in stabilizing such interactions and enables rationalizing the different topologies observed in terms of competition between primary and secondary exchange channels. Also, the formation and breaking of a hydrogen bond during proton transfer reactions has been analyzed by utilizing an atomic decomposition of global quantities (from Conceptual DFT), the new decompositionscheme being based on the QTAIM partition and the IQA energy decomposition. This approach allows following the contribution of every atom to the reactivity of the whole system along a reaction path, introducing a new way of characterizing energy barriers and transition.