Chiral Self‐Assembly of Biphenyl‐Cored Carbohydrate Bolaamphiphiles and Molecular Dynamic Simulation‐Derived Mechanistic Insights

The presence of multiple chiral centers and constitutions in carbohydrates opens up a facile access to uncover supramolecular chirality properties in self-assembled carbohydrate bolaamphiphiles. In this work, bolaamphiphiles are presented that present monosaccharide moieties at the termini of an internal p,p'-biphenyl core segment. The core segment exhibits a planar twisting, which promotes chiral self-assembly of the bolaamphiphiles. α-D-Mannopyranoside-biphenyl-mannopyranoside bolaamphiphile self-assembles with a helicity, whereas α-L-rhamnopyranoside-biphenyl-rhamnopyranoside inverts this helicity in aq. solutions. The propensity for the emerging supramolecular chirality depends on the pH of the solution, where alkaline pH retains the helicity, whereas acidic pH abolishes the same. The concentration dependence of the chiral self-assembly properties is evaluated in solution. Molecular dynamics (MD) simulation studies reveal the thermodynamic states and interactions crucial for the self-assembly of biphenyl and the correlated terphenyl bolaamphiphiles. Morphological studies by microscopies ascertain the helicities in the solid state. The multivalent presentation of α-D-mannopyranoside in the self-assembled structures permits complexation with a relevant lectin, as assessed by turbidity assays. Cytotoxicity assessments of biphenyl bolaamphiphiles on the MCF-7 cell line reveal that the α-L-rhamnopyranoside bolaamphiphile has an IC₅₀ of 89.6 ± 3.3 µm, indicating higher toxicity compared to the α-D-mannopyranoside bolaamphiphile, which has an IC₅₀ greater than 100 µm.