C-amidation of substituted β³ oligoamides yields novel supramolecular assembly motif

Abstract

N-acylated substituted β 3 oligoamides are known to form unique supramolecular nanorods based on a 3-point hydrogen bond self-assembly motif. This motif is an intermolecular extension of the hydrogen bonding network that stabilizes the 14-helix secondary structure unique to β 3 oligoamides. Acetylation of the N-terminus of the molecule provides the necessary third hydrogen bond pair of the motif. Here, the possibility of introducing the third hydrogen bond pair via amidation of the C terminus is investigated. While similar in purpose, this modification introduces a chemically distinct new self-assembly motif, also removing the bulky carboxyl group that does not fold into the 14 helix positioning instead as a side chain. Three substituted β 3 oligoamide variants with the base sequence LIA (where the letters denote β 3 residues with side chains analogous to α amino acids) were compared: N-acylated Ac-β 3 [LIA] as a reference, C-amidated β 3 [LIA]-CONH 2 , and β 3 [LIA] with free unmodified N and C termini as a negative control. The three variants were dissolved in water to promote self-assembly. The self-assembly was characterised using mid-and far-infrared spectroscopy, small angle x-ray scattering (SAXS) and atomic force microscopy (AFM). IR measurements confirmed that all three samples were in a similar conformation, consistent with pseudo 14-helical secondary structures. Far-infrared spectroscopy measurements of β 3 [LIA]-CONH 2 showed distinct peaks consistent with highly organised skeletal modes, i.e. regular supramolecular assembly, that was largely absent from the other two oligoamides. Modelling of SAXS data is consistent with elliptical cylinder structures resulting from nanorod bundling for both β 3 [LIA]-CONH 2 and Ac-β 3 [LIA], but not in the unmodified sample. Consistently, AFM imaging showed large nanorod bundling structures in β 3 [LIA]-CONH 2 , varied bundling structures in Ac-β 3 [LIA], and only aggregation in β 3 [LIA]. Amidation showed much more organised and robust assembly compared to acetylation, providing a new, easy to synthesize self-assembly motif for helical nanorod assembly that is similar but distinct to N-acylation

Controllable hierarchical self-assembly: systematic study forming metallosupramolecular frameworks on the basis of helical beta-oligoamides

“…18 The mechanisms of head-to-tail self-assembly of helical beta oligoamide units were established previously. [19][20][21][22][23][24] Supramolecular self-assembly of b 3 oligoamides is achieved by modification of either termini to form at least one amide moiety in terminal position. 19,24 The resulting geometrically defined three point hydrogen bonding motif implements supramolecular specificity of the attachment, yielding helical nanorods that can reach millimeter lengths and with only B0.5 nm diameter with high stability 19 and the ability to coassemble.…”

“…[19][20][21][22][23][24] Supramolecular self-assembly of b 3 oligoamides is achieved by modification of either termini to form at least one amide moiety in terminal position. 19,24 The resulting geometrically defined three point hydrogen bonding motif implements supramolecular specificity of the attachment, yielding helical nanorods that can reach millimeter lengths and with only B0.5 nm diameter with high stability 19 and the ability to coassemble. 23 It was also demonstrated that the terminal loops are sufficient to propagate self-assembly, with the option of including a ''payload'' of other (i.e.…”

“…The secondary level of the hierarchical self-assembly is a three-point hydrogen bonding motif that attaches each oligoamide unit (head to tail) via hydrogen bonding, thus, forming nanorods/fibrils. 19,20,24 The highest level of this hierarchy is achieved by metal coordination between fibrils. 17 Predicting geometric preferences for transition metal ligand placement is important in the design of the highest level of hierarchy in this system, 30 and difficult.…”

“…Through knowledge of similar beta-oligoamides we expected the neat 3H to form a fibrous assembly. 16,17,[22][23][24] The addition of metals is expected to form thin films if coordination takes place with the oligoamide, in which individual nanorods are not distinguishable. The presence of fibrous assemblies akin to the neat 3H indicate incomplete coordination or no coordination at all.…”

“…The secondary level of the hierarchical self-assembly is a three-point hydrogen bonding motif that attaches each oligoamide unit (head to tail) via hydrogen bonding, thus, forming nanorods/fibrils. 19,20,24 The highest level of this hierarchy is achieved by metal coordination between fibrils. 17…”