Molecular Interaction Regulated Assembly of Engineered Amphiphiles and Protein

Amphiphiles are prominent synthetic systems explored for wide-ranging mesoscopic structures with close relevance in nanotechnology and biomedicine. However in majority examples, their immiscibility driven aggregation does not endow precision in important structural parameters including size, morphology or functional group display. In contrast, directional molecular interactions (primarily H-bonding) form the basis of structural evolution and functional perfection of biomacromolecules such as enzymes, DNA or RNA in which alteration in the sequence of a single amino acid or mismatch in one base-pair could make vital contribution to the overall structure and function. We have recently introduced assembly of supramolecularly engineered amphiphilic macromolecules (SEAM) [1-3] with precise internal order. In these systems, a supramolecular structure directing unit (SSDU) has been appended with a hydrophilic coil-like polymer. The SSDU is made of a H-bonding functional group (hydrazide/ amide) and a NDI-chromophore. By synergistic H-bonding and aromatic interaction, the SSDU pre-assembles and thus the subsequent step, involving hydrophobic association of the wedge, becomes a function of the first step (dictated by molecular interaction). Therefore the mesoscopic structure can be regulated by the distinct nature of the molecular interaction involved in the first step by fully ignoring the packing parameters. Consequently, two amphiphilic block copolymers having identical chemical structure and same hydrophobic/ hydrophilic balance organize to form distinctly different assemblies (polymersome or cylindrical micelle) depending on the nature of the single H-bonding functional group (hydrazide or amide) of the SSDU. So prominent is the motivation for self-selection that in a mixture of two such polymers, self-sorting can be noticed although they differ merely by a SINGLE H-bonding functional group. Recently, we have established that the design can be extended to wide-ranging polymers including charged polymers and the same rule applies. In fact, the hydrophilic polymer, when replaced with a protein, still the SSDU could direct highly stable (no denaturation upto 90⁰ C) nano-structured assembly of the supramolecularly engineered protein (SEP) without disrupting its enzymatic activity.[4] Isothermal calorimetric (ITC) studies [3] reveal prominent entropy motivation in highly stable self-assembly of the SEAMs/ SEB having merely 4-6 wt % hydrophobic content. The first part of the presentation will highlight these results. The second part of the presentation will highlight directional polymersome assembly of unsymmetric bola-shape π-amphiphiles regulated by H-bonding and consequences on functional group display and biomolecular recognition by multivalent interaction.[5-7] References : 1. A. Das and S. Ghosh, Macromolecules 2013, 46, 3939-3949. 2. P. Pramanik, D. Ray, V. K. Aswal and S. Ghosh, Angew. Chem. Int. Ed. 2017, 56, 3516-35202. 3. A. Sikder, D. S. Ray, V. K. Aswal and S. Ghosh, Chem. Eur. J. 2019, 25, 10464–10471. 4. P. Dey, P. Rajdev, P. Pramanik and S. Ghosh, Macromolecules 2018, 51, 5182−5190. 5. A. Sikder, D. S. Ray, V. K. Aswal and S. Ghosh, Angew. Chem. Int. Ed. 2019, 58, 1606-1611. 6. A. Sikder, J. Sarkar, R. Barman and S. Ghosh, J. Phys. Chem. B 2019, 123, 7169−7177. 7. A. Sikder, A. Das, and S. Ghosh, Angew. Chem. Int. Ed. 2015, 54, 6755-6760.