Synthesis of pharmaceutical co-crystals and functionalized polymers for micropollutant remediation

Crystal engineering, as a rapidly growing and developing research field, aims at design and synthesis of new solids with desired physical and chemical properties via reliable intermolecular interactions such as hydrogen bonds, halogen bonds, π‧‧‧π staking, and coordination bonds. We have applied crystal engineering strategies to the design and synthesis of bipyridine based pharmaceutical co-crystals where we confirm that the supramolecular hydrogen-bond synthon behaviour of the selected NSAIDs is reliable, regardless of minor changes to bipyridine co-formers. A rarity of motif in acid-bipyridine co-crystals was reported, where we observed the expected COOH···N synthon breakdown and formation of a pyridyl dimer. Also, a unique robust supramolecular complex of diclofenac was synthesized and can be used for crystal-to-crystal solvent exchange while maintaining crystallinity. We have also applied principles of crystal engineering to the predictions in co-crystals of acetazolamide (ACZ) and co-crystal formers (CCFs) containing either only aromatic nitrogen acceptor sites or both acceptor and donor moieties. The pKa values, basicity of CCFs, and geometric complementarity all play a crucial role in predicting synthon formation in ACZ co-crystals. We demonstrate a behavior rarely observed in co-crystal ACZ‧BPP, where 1,3-di(4-pyridyl)propane (BPP) as a CCF engages with ACZ at both the sulfonamide and amide donor sites. We utilize co-crystallization strategies to synthesize salts of trimethoprim (TMP) and monopyridines. All salts exhibit higher aqueous solubility than TMP. Specifically, two salts are ten times more soluble than TMP. One salt-hydrate is promising as CCF nicotinic acid (NA) is on the GRAS list and the solid exhibits high aqueous solubility, good thermal stability, and good stability under ambient conditions. This dissertation will also focus on the design and synthesis of polymer materials that can bind and remove micropollutants from water. We synthesized both linear and cross-linked polymers including both hydrophobic and hydrophilic polymers. Concentration of micropollutants such as propranolol-HCl (PPL-HCl) and 2-naphthol (2NO) successfully decrease by varying degrees from water after binding over a time frame of 1-4 h.