Positive Cooperativity in the Template-Directed Synthesis of Monodisperse Macromolecules

Two series of oligorotaxanes R and R′ that contain −CH2NH2+CH2– recognition sites in their dumbbell
components have
been synthesized employing template-directed protocols. [24]­Crown-8
rings self-assemble by a clipping strategy around each and every recognition
site using equimolar amounts of 2,6-pyridinedicarboxaldehyde and tetraethyleneglycol
bis­(2-aminophenyl) ether to efficiently provide up to a [20]­rotaxane.
In the R series, the −NH2+– recognition sites are separated by trismethylene bridges,
whereas in the R′ series the spacers are p-phenylene linkers. The underpinning idea here is that
in the former series, the recognition sites are strategically positioned
3.5 Å apart from one another so as to facilitate efficient [π···π]
stacking between the aromatic residues in contiguous rings in the
rotaxanes and consequently, a discrete rigid and rod-like conformation
is realized; these noncovalent interactions are absent in the latter
series rendering them conformationally flexible/nondiscrete. Although
in the R′ series, the [3]-, [4]-, [8]-, and [12]­rotaxanes
were isolated after reaction times of <5–30 min in yields
of 72–85%, in the R series, the [3]-, [4]-, [5]-,
[8]-, [12]-, [16]-, and [20]­rotaxanes were isolated in <5 min to
14 h in 88–98% yields. It follows that while in the R′ series the higher order oligorotaxanes are formed in lower yields
more rapidly, in the R series, the higher order oligorotaxanes
are formed in higher yields more slowly. In the R series,
the high percentage yields are sustained throughout, despite the fact
that up to 39 components are participating in the template-directed
self-assembly process. Simple arithmetic reveals that the conversion
efficiency for each imine bond formation peaks at 99.9% in the R series and 99.3% in the R′ series. This
maintenance of reaction efficiency in the R series can
be ascribed to positive cooperativity, that is, when one ring is formed
it aids and abets the formation of subsequent rings presumably because
of stabilizing extended [π···π] stacking
interactions between the arene units. Experiments have been performed
wherein the dumbbell is starved of the macrocyclic components, and
up to five times more of the fully saturated rotaxane is formed than
is predicted based on a purely statistical outcome, providing a clear
indication that positive cooperativity is operative. Moreover, it
would appear that as the R series is traversed from the
[3]- to the [4]- to the [5]­rotaxane, the cooperativity becomes increasingly
positive. This kind of cooperative behavior is not observed for the
analogous oligorotaxanes in the R′ series. The
conventional bevy of analytical techniques (e.g., HR-MS (ESI) and
both 1H and 13C NMR spectroscopy) help establish
the fact that all the oligorotaxanes are pure and monodisperse. Evidence
of efficient [π···π] stacking between contiguous
arene units in the rings in the R series is revealed
by 1H NMR spectroscopy. Ion-mobility mass spectrometry
performed on the R and R′ series
yielded the collisional cross sections (CCSs), confirming the rigidity
of the R oligorotaxanes and the flexibility of the R′ ones. The extended [π···π]
stacking interactions are found to be present in the solid-state structures
of the [3]- and [4]­rotaxanes in the R series and also
on the basis of molecular mechanics calculations performed on the
entire series of oligomers. The collective data presented herein
supports our original design in that the extended [π···π]
stacking between contiguous arene units in the rings of the R series of oligorotaxanes facilitate an essentially rigid
rod-like conformation with evidence that positive cooperativity improves
the efficiency of their formation. This situation stands in sharp
contrast to the conformationally flexible R′ series
where the oligorotaxanes form with no cooperativity.