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Quantifying Cooperativity in Non-Covalent Networks https://doi.org/10.17863/CAM.115422 https://doi.org/10.17863/CAM.115422 Hanna, Fergal 0000000293769921 Hunter, Christopher Non-covalent interactions are important in biological, material, systems, and supramolecular chemistry. Some quantification of cooperativity in networks of non-covalent interactions has been done in the literature, but these experiments are often complex and not easily applicable to many different types of functional group. The work in this thesis builds on previous work in the Hunter group on quantifying the cooperativity in functional groups capable of forming two H-bonds by expanding it to new functional groups. A cooperativity parameter, κ, that measures the relationship between two H-bonds to the same functional group was introduced previously in studies of phenols. The values of κ can be determined by using an intramolecular and intermolecular H-bond to the functional group of interest and measuring the relationship between them. The stabilisation due to cooperativity is equal to the strength of a H-bond between the intramolecular and intermolecular groups multiplied by κ. The methodology was first used in this thesis on amides with an intramolecular H-bond to a phenol and an intermolecular H-bond to a phosphine oxide, the stabilisation from cooperativity was found to be worth up to 6 kJ mol-1 . Amides with an intramolecular H-bond to a pyridine and an intermolecular H-bond to perfluoro-tert-butanol (PFTB) were also studied. In both cases κ for an amide was found to be +0.20. Density-functional theory (DFT) calculations were used to predict the cooperativity, and provided a good match to the data, showing that the cooperativity from the intramolecular H-bond arises from properties of the isolated, individual molecules. The DFT calculations capture both changes in polarity of the amide group and through-space electrostatic interactions with the intramolecular H bonding group (phenol or pyridine). The same scaffold with an intramolecular H-bond to a pyridine was used to study anilines and sulfonamides. The value of κ for the anilines when H-bonding intermolecularly to a phosphine oxide was found to be -0.10 as the two H-bonds are negatively cooperative, either due to through-space repulsion or changing polarity of the NH groups. The cooperativity effect is well predicted by DFT for the anilines. For the sulfonamides κ was found to be +0.16 when H-bonding intermolecularly to PFTB, which means less positive cooperativity than the amide. The DFT prediction of the sulfonamides was not quantitatively correct but predicted the qualitative trend. A similar approach was used to investigate the effect of an n-π* interaction on the H-bond acceptor properties of an amide, but only weak cooperativity between the n-π* and H-bond properties was observed. v Finally, the DFT prediction of κ values was carried out on over 30 more functional groups. The results of this allowed insight into the relationship between κ and functional group type, or κ and the geometry of the system. Smaller ring sizes for the intramolecular H-bond lead to increased magnitude of κ. Nitrogen and oxygen H-bond acceptors were found to show greater cooperativity effects than sulfur H-bond acceptors. Increased number of bonds between the sites forming the intramolecular and intermolecular H-bonds was found to attenuate cooperativity in functional groups with an intramolecular H-bond acceptor, but showed less of a relationship for those with an intramolecular H bond donor. From the predicted κ values future experimental work can be identified to further understand the basis of the cooperativity observed experimentally in this thesis. University of Cambridge 2024-06-13 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/379274 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/10c15934-59e2-4d06-9122-a78d5f391b1f/download 6bfbe09c674c61d9e6fb388a78b59890 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/126f985a-bacc-4652-99f9-4bba68c2b90f/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Organic Chemistry Chemistry Physical Organic Chemistry Non-covalent interactions Supramolecular Chemistry H-bonding Hydrogen bonds