Letter Cite This: Org. Lett. 2018, 20, 5486−5489
pubs.acs.org/OrgLett
Effects of Oligomer Length, Solvents, and Temperature on the SelfAssociation of Aromatic Oligoamide Foldamers Yongye Zhao,†,‡,∇ Alan L. Connor,‡,∇ Thomas A. Sobiech,‡ and Bing Gong*,†,‡ †
College of Chemistry, Beijing Normal University, Beijing 100875, China Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States
‡
Org. Lett. 2018.20:5486-5489. Downloaded from pubs.acs.org by KAOHSIUNG MEDICAL UNIV on 09/08/18. For personal use only.
S Supporting Information *
ABSTRACT: The effects of oligomer length, solvent, and temperature on the self-association of stably folded short aromatic oligoamide are probed. With large flat surfaces, these aromatic oligoamides undergo stacking interaction with strength that increases nonlinearly with oligomer lengths. Opposite to typical aromatic stacking, the stacking of these molecules is enhanced in solvents of low polarity, but it is greatly weakened in polar solvents, especially those with hydrogen bond donors, and it is very sensitive to changes in temperature.
A
remain to be explored, the influence of other factors including oligomer length, concentration, and temperature, on the selfassociation of these foldamers is unknown.
romatic stacking plays a critical role in molecular association,1 leading to the supramolecular assemblies known today. For example, aromatic molecules, especially those having large, flat surfaces, have a tendency to undergo cofacial stacking to form columnar stacks.2,3 Foldamers4 with backbonerigidified aromatic oligoamides adopting stably folded shapes also have flat surfaces defined by coplanar aromatic rings and amide linkages.5 We created aromatic oligoamides with flat, tapelike backbones adopting stably folded conformations containing internal cavities. 1d,5a,6,7 One series of such oligoamide foldamers consist of meta-linked benzene residues that are connected with secondary amide groups.7 With highly stable intramolecular hydrogen bonds5 that limit bond rotation and force coplanarity on the benzene residues and amide groups, our oligoamide foldamers, depending on their lengths, adopt crescent or helical shapes that have internal cavities and flat surfaces. Incapable of self-associating via hydrogen-bonding interactions because their amide protons engage in favorable intramolecular hydrogen-bonding interactions,8 our oligoamide foldamers, along with their macrocyclic counterparts, still aggregate strongly.9,10 Short oligomers of this series, which adopt crescent shapes, were observed to undergo anisotropic assembly in the solid state to form columnar stacks.10 Similar to polycyclic aromatics, the molecules of these shape-persistent oligoamides seem to self-associate also by stacking with each other. Compared to the stacking of aromatic hydrocarbons, which is promoted by polar solvents such as methanol and water but is weakened in low polar solvents such as benzene and chloroform,2,3 the aggregation of our oligoamides seems to involve different solvent effects, being enhanced in nonpolar solvents and weakened in polar solvents. Besides solvent effects that © 2018 American Chemical Society
Herein, we report results from an investigation on the aggregation of aromatic amides 1, 2, 3, 4, and 5, consisting of 1, 2, 4, 6, and 8 meta-linked benzene residues. Oligoamides 2, 3, and 4 adopt crescent conformations, while octamer 5 has a length that allows it to adopt a helical conformation of just over one turn.7 Being flanked by two amide groups that are attached in opposite orientations, the basic residues of 1−5 are the same electronically, allowing the aggregation of these amides to be directly compared. Our study indicates that the self-association of these shape-persistent molecules is facilitated by factors distinctly different from those that promote typical aromatic stacking. Self-aggregation is drastically enhanced for oligomers with six or more residues, and it is promoted in solvents of lower polarity such as chloroform, but weakened or interrupted in solvents of higher polarity. In the micromolar concentration range, a pronounced temperature effect on the strong aggregation of octamer 5 was revealed by fluorescence spectroscopy. Compounds 1−5 were synthesized based on the procedures we established11 and gave satisfactory analytical data (see the Supporting Information). Received: July 31, 2018 Published: August 17, 2018 5486
DOI: 10.1021/acs.orglett.8b02438 Org. Lett. 2018, 20, 5486−5489
Letter
Organic Letters The different propensities of 1−5 for self-association was indicated by their 1H NMR spectra recorded in CDCl3. Figure 1
Table 1. Values of Chemical Shifts (ppm) of Amide and Aromatic Protons of Aromatic Amides 1, 2, and 3a
Chemical Shifts (ppm) proton
1
2
3
c1 d c2, c3, c4 a1, a2, a3, a4 b1, b2, b3, b4
7.516 7.925
7.261 7.847 9.850 6.501, 6.555 8.871, 9.088
7.349 7.890 9.594, 9.876, 9.907 6.481 (2H), 6.528, 6.566 8.219, 8.862, 9.098 (2H)
6.564 8.868
Figure 1. Partial 1H NMR spectra of aromatic amides 1−5 (1 mM each) in CDCl3 (25 °C, 500 MHz).
a
shows the partial 1H NMR spectra (from 5.5 ppm to 10.5 ppm) that include the amide and aromatic proton resonances of the five aromatic amides. In contrast to the sharp and well-dispersed proton resonances of 1 and 2, and the slightly broadened but still well-dispersed signals of tetramer 3, the peaks of both hexamer 4 and octamer 5 are severely broadened and unresolved. The observed difference in the 1H signals of these aromatic amides indicate that 1, 2, and 3 exist mainly or entirely as well-defined, discrete species, while the longer 4 and 5 undergo much stronger self-association, leading to aggregates that result in linebroadening of the 1H resonances. The 1H resonances of 1 recorded from 0.5 mM to 124 mM, those of 2 from 0.5 mM to 116 mM in CDCl3, and the ones of tetramer 3 from 0.3 mM to 49 mM, remain well-dispersed, suggesting that the aggregation of these aromatic amides, if any, is rather weak (Figures S1a−S1c in the Supporting Information). The signals of 1 undergo almost no shift in the wide concentration range examined, indicating that this one-residue amide does not self-associate. Compared to those of 1, the signals of 2 and 3 undergo small but noticeable shifts in CDCl3, even at 1 mM (see Table 1), with protons c1, d, and a1−a4 of 2 and 3 showing upfield shifts that are consistent with aromatic stacking interactions.12 In comparison to the weak self-association of 2 and 3 shown by their well-dispersed 1H NMR peaks, the strong aggregation of hexamer 4 (from 5 mM to 0.75 mM) and octamer 5 (from 15 mM to 1 mM) is indicated by their broadened and unresolved 1 H signals unaffected by concentration (see Figures S1d and S1e in the Supporting Information). Although the severely broadened peaks of the 1H resonances of 4 and 5 cannot be assigned to the corresponding protons, examining the amide and aromatic regions of the 1H NMR spectra of these two oligoamides indicate that several resonances belonging to aromatic protons a1, a2, ..., and b1, b2, ..., seem to shift to positions that are significantly upfield, relative to protons a1 and b1 of 1. Thus, in comparison to the weak self-association of 2 and 3, strong aggregation that remains uninterrupted within the concentration range of the experiments was observed for 4 and 5. To probe the effect of temperature on the aggregation of 4 and 5, the 1H NMR spectra of these two oligoamides were recorded
at 0.5 mM in 1,1,2,2-tetrachloroethan-d2 (C2D2Cl4) from 25 °C to 90 °C (see Figure S2 in the Supporting Information). In this wide temperature range, the 1H signals of 4 or 5 show no noticeable improvement in their line width, with all the peaks remaining poorly resolved, which indicates the extraordinary stability of the aggregates formed by 4 or 5. Only small upfield shifts (
