Probing Molecular Chirality on the Self-Assembly and Gelation of Naphthalimide-Conjugated Dipeptides

J Phys Chem B. 2023 Jun 1;127(21):4808-4819. doi: 10.1021/acs.jpcb.3c01273. Epub 2023 May 17.

Abstract

In this work, 1,8-naphthalimide (NMI)-conjugated three hybrid dipeptides constituted of a β-amino acid and an α-amino acid have been designed, synthesized, and purified. Here, in the design, the chirality of the α-amino acid was varied to study the effect of molecular chirality on the supramolecular assembly. Self-assembly and gelation of three NMI conjugates were studied in mixed solvent systems [water and dimethyl sulphoxide (DMSO)]. Interestingly, chiral NMI derivatives [NMI-βAla-lVal-OMe (NLV) and NMI-βAla-dVal-OMe (NDV)] formed self-supported gels, while the achiral NMI derivative [NMI-βAla-Aib-OMe, (NAA)] failed to form any kind of gel at 1 mM concentration and in a mixed solvent (70% water in DMSO medium). Self-assembly processes were thoroughly investigated using UV-vis spectroscopy, nuclear magnetic resonance (NMR), fluorescence, and circular dichroism (CD) spectroscopy. A J-type molecular assembly was observed in the mixed solvent system. The CD study indicated the formation of chiral assembled structures for NLV and NDV, which were mirror images of one another, and the self-assembled state by NAA was CD-silent. The nanoscale morphology of the three derivatives was studied using scanning electron microscopy (SEM). In the case of NLV and NDV, left- and right-handed fibrilar morphologies were observed, respectively. In contrast, a flake-like morphology was noticed for NAA. The DFT study indicated that the chirality of the α-amino acid influenced the orientation of π-π stacking interactions of naphthalimide units in the self-assembled structure that in turn regulated the helicity. This is a unique work where molecular chirality controls the nanoscale assembly as well as the macroscopic self-assembled state.