Tuning the Stacking Properties of C₃‐Symmetrical Molecules by Modifying a Dipeptide Motif

Abstract

C3-symmetrical molecules are described which consists of a 1,3,5-benzenetricarboxamide core extended with dipeptide fragments bearing peripheral mesogenic groups. Small structural modifications in the dipeptide fragment have been performed to demonstrate their influence on the stability of the stacks and on the order within the self-assemblies formed. Seven C3-symmetrical discs have been investigated, all with different combinations of glycine, L- and/or D-phenylalanine in the dipeptide fragments. Characterization of these discotics in the neat state using differential scanning calorimetry (DSC), X-ray diffraction (XRD) and polarized optical microscopy (POM) and in solution with circular dichroism (CD), UV-visible spectroscopy, low-concentration proton nuclear magnetic resonance and IR spectroscopy reveals that there is a clear trend in the stack stability, going from the glycine-phenylalanine motifs to the phenylalanine-phenylalanine ones. The combination of a larger hydrophobic core, more confinement of space and the possibility of additional pi-pi interactions leads to more stable stacks. Surprisingly, the weakest stacks consist of discotics of which the center is extended with L-phenylalanyl-glycines and not of discotics of which the center is extended with the glycyl-L-phenylalanine sequences. Furthermore, the XRD investigations show that it is difficult to form well-ordered self-assemblies in the neat state. And, CD measurements point out that some of the discs have a very complex energy landscape in solution. These observations suggest that small differences in the balance between the secondary interactions originating from the benzenetricarboxamide core and the dipeptide fragments, have a strong influence on the order within the stack. From these results it can be concluded that subtle modifications in the peptide fragments of the discs cause significant changes in the stacking properties, stressing the importance of understanding the self-assembly mechanism of each discotic in order to clarify its self-assembly behavior.

Controlled Supramolecular Oligomerization of C3‐Symmetrical Molecules in Water: The Impact of Hydrophobic Shielding

“…l-Lysine-functionalized DTPA was allowed to react with N-benzyloxycarbonyl-l-phenylalanine using 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) as a coupling reagent and N,N-diisopropylethylamine (DiPEA) as a base; these conditions are known to prevent racemization of the activated amino acid. [36,52] The benzyloxycarbonyl group was removed by catalytic hydrogenation, and the resulting intermediate was reacted with 0.30 molar equivalents of trimesic chloride in the presence of triethylamine as a base. Removal of the tertbutyl groups and complexation of the free DTPA ligands with Gd III or Y III gave compounds 2 a and 2 b (Scheme S2).…”

“…[34] We introduced order into the obtained architectures by relying on the well-known C 3 -symmetrical benzene-1,3,5-tricarboxamide (BTA) unit, which in solution has a strong tendency to form columnar aggregates based on a triple hydrogen-bonding motif. [35][36][37][38] By introducing highly charged peripheral Gd III -DTPA (diethylene tri-A C H T U N G T R E N N U N G amine pentaacetic acid) groups we managed to restrict the one-dimensional growth of the objects [34] in a process that can be referred to as frustrated growth. [39,40] In this study, a series of structural variations in the polymerizing hydrophobic core of discotic amphiphiles is described (Figure 1), highlighting the requirement for hydrophobic shielding of the hydrogen-bonding motif.…”

Controlling the growth and shape of chiral supramolecular polymers in water

“…The molecular design of our self-assembling unit is based on the well-studied C 3 -symmetrical benzene-1,3,5-tricarboxamide (BTA) core that directs the self-assembly into triple hydrogenbonded helices (40)(41)(42). This moiety was extended with a fluorinated L phenylalanine and an aminobenzoate spacer, thereby significantly increasing the stability of the assemblies via additional hydrogen bonding, π-π interactions, and solvophobic effects ( Fig.…”

Sterically demanding benzene-1,3,5-tricarboxamides: tuning the mechanisms of supramolecular polymerization and chiral amplification

“…11 In the first case of isodesmic self-assembly behavior, the association constants for the first and subsequent association steps are equal to one another. 15,16 The exact reason for the observed differences in the self-assembly process depending on the nature of the side chains has not been fully elucidated, although the ability to form strongly polarised intermolecular hydrogen bonds in the aggregates appears to play an important role in the cooperative self-assembly behavior. In the second situation, the association constants for the first few monomer additions are less favorable than all subsequent monomer additions.…”