Synthesis and Self-Assembly Studies of Carbohydrate-Conjugated Oligo-p-Phenylenes

Abstract

The structural diversity of carbohydrate derivatives is amplified further by their strong tendency to self-assemble in aq. solutions, provided the molecular constitution and environmental conditions favor. Glycostructures containing aromatic moieties exhibit self-assembly behavior primarily driven by π–π stacking interactions among aromatic rings, hydrogen bonding between carbohydrate moieties and CH–π interactions between the carbohydrate and aromatic segments. The aromatic moieties derivatizing the carbohydrate segment influence significantly the chiral self-assembly processes and lead to varied nanostructures. Both biphenyl- and terphenyl-based carbohydrate bolaamphiphiles undergo self-assembly to form chiral supramolecular structures. These chiral aggregates display aggregation-induced emission (AIE) in aq. solutions. The circular dichroism (CD) intensity markedly increases from biphenyl to terphenyl derivatives. In contrast, phenyl-cored carbohydrate bolaamphiphiles do not exhibit supramolecular chirality. A notable inversion in supramolecular chirality is observed when the carbohydrate configuration is altered from D- to L-. External stimuli such as pH and temperature play a crucial role in modifying the chiral self-assembly process in aqueous media. Molecular dynamics simulations provide insight into the microstructures involved during the early stages of self-assembly growth. Turbidity assays indicate the structural stability and cross-linking of carbohydrate moieties with lectins, specifically mannose-specific concanavalin A (Con A). Rhamnose, possessing an L-configuration that mirrors the D-configuration of mannose, is rarely present on the surface of mammalian cells, such as the MCF-7 cell line used in the study. The absence of native recognition and appropriate stereochemistry contributes to the increased cytotoxicity of rhamnose-based bolaamphiphiles. Short-chain oligo-p-phenylenes are employed as hydrophobic segments in carbohydrate bolaamphiphiles, whereas longer-chain oligo-p-phenylenes are utilized as conducting polymers. The controlled synthesis of oligo-p-phenylene oligomers is achieved using multivalent dendritic PdII catalysts. These oligomers undergo Vilsmeier–Haack formylation, introducing formyl groups that enhance their solubility in apolar solvents. The functionalized oligomers are then evaluated for their biochemical behavior in cell lines, with cellular internalization monitored via fluorescence microscopy. Overall, the results presented in the Thesis demonstrate that: (i) biphenyl- and terphenyl-based carbohydrate bolamphiphiles self-assemble in aq. solution to form chiral supramolecular structures; (ii) a multivalent dendrimer-supported PdII catalyst offer a control of the chain length of oligo-p-phenylenes and the resulting oligomers are further functionalized to enhance their solubility, making them suitable for cell imaging studies.