Fig. 1 (a) Tri-ethylene glycol substituted o-PE ester oligomers.
Tetramer 1 (n = 1), Pentamer 2 (n = 2), Hexamer 3 (n = 3). Each
ring (Rn) has three protons that are labeled respective to their
J-coupling and splitting pattern: a (8.4 Hz, d); b (2.1 Hz, d); and c
(8.4 Hz and 2.1 Hz, dd). (b) Four of the many potential conformations
of 3. The ‘correctly’ folded helical conformer is highlighted.
titration was 0 ppm, then the change in average ppm of the
protons on each ring (D ppm) during the titration was deter-
mined. Each point on the graph represents the average D ppm
value for the protons of each ring. Fig. 2a shows the protons on
rings R1,2,4,5 of 2 shift upfield as CD3CN is added, while only R3
remains at B 0 D ppm. Similarly, all six rings of 3 shift upfield as
CD3CN is added. These upfield shifts are in the opposite direction
of the natural tendency for these protons as model compounds
that cannot fold shift downfield when CD3CN is added to
CDCl3.2h Here, the results are consistent with p–p stacking and
the upfield shift caused by this interaction as the oligomers adopt a
helical conformation. The solvent titration results agree fully with
the expectations of a ‘correctly’ folded helical conformation for
both 2 and 3. As was the case with the previously reported
tetramers, these solvent titrations of 2 and 3 never flattened out as
the concentration of CD3CN approached 100% suggesting that
the solution always contained an equilibrium between folded and
unfolded oligomers. Since it was not possible to increase the
volume percent of CD3CN further, we decided to examine the
influence of temperature on the aromatic protons’ chemical shift.
It was speculated that if an equilibrium of folded and
unfolded structures coexisted in 100% CD3CN at room
temperature then cooling the solution would see an increased
upfield shift of the protons as the equilibrium was shifted
toward the folded structure. In contrast, heating the solution
would shift the protons back downfield as the equilibrium
moved toward the unfolded confirmation. As shown in Fig. 3a
and b, temperature titrations (À26 to 77 1C in CD3CN) were
performed to study these oligomers and are plotted as the
D ppm versus temperature. For oligomer 2, these temperature
titrations show that only the protons of R3 remain unshifted as
the temperature is changed by 100 1C while all the protons on
R1,2,4,5 shift. Starting from 25 1C, as the system is cooled the
protons shift upfield and as the system is heated the protons
shift downfield. Similarly, for 3 the temperature study makes it
very clear that all of the protons on R1–6 shift downfield during
heating from À26 to 77 1C. This change would only occur if all
the aromatic rings of 3 were associated intramolecularly via
p–p stacking of a compact helix in CD3CN. These observa-
tions support the boxed conformation shown in Fig. 1b as the
major conformer in solution and rule out the other possible
Scheme 2 Synthesis of oligomers 1, 2, and 3 by stepwise Sonagashira
couplings and deprotection steps. (i) PdCl2(PPh3)2, CuI, TEA, THF,
55 1C (ii) CH3I, I2, 110 1C (iii) TBAF, THF, 0 1C (iv) 10,
PdCl2(PPh3)2, CuI, TEA, THF, 55 1C (v) TBAF, THF, 0 1C/10,
PdCl2(PPh3)2, CuI, TEA, THF, 55 1C (vi, vii) TBAF, THF, 0 1C/12,
PdCl2(PPh3)2, CuI, TEA, THF, 55 1C.
to as the ‘correctly’ folded helix since this structure has all six
rings involved in p–p stacking. However, since this requires an
entropic penalty, the ability of this hexamer to adopt less ‘‘well-
folded’’ conformations such as those shown in Fig. 1b were
considered. Three other possible structures are illustrated in which
either R5 and/or R6 are not folded into the helical conformation.
As a result of this increasingly complicated landscape, it was
important to consider experimental methods that could distin-
guish between these partially folded structures and the ‘correctly’
folded helix shown in the box of Fig. 1b. This possibility of ‘‘mis-
folded’’ structures appeared important since computational cal-
culations showed that while longer o-PE helical conformations
were lower in energy, the energy difference between fully and
partially folded structures was relatively small.6b
Returning to the previous experimental observations that
confirmed folding of 1, in which only the terminal rings R1 and
R4 shifted upfield in CD3CN, it seemed reasonable that
‘correctly’ folded helical conformations of 2 and 3 would have
four and six rings, respectively, that experience upfield shifts
due to p–p stacking. More specifically, R1,2,4,5 of 2 and R1–6 of
3 would shift upfield leaving only R3 of 2 unshifted. Using
multiple NMR methods (COSY and HMBC), each aromatic
proton and its position in the oligomer has been assigned6c
allowing absolute tracking of each individual proton.
The 1D NMR results of solvent titrations (CDC13 to
CD3CN) for 2 and 3 are shown in Fig. 2a and b. The data
was normalized, as our previous report,2d so that the average
ppm of the protons on each ring at the beginning of the
ꢀc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2008
New J. Chem., 2008, 32, 676–679 | 677