Applications of Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 413

It appeared that the most sensitive detection occurred when most of the foldamers just
became unfolded.

The principle of preorganization has brought great advancement to supramolecular
chemistry over the last several decades. The idea originated from the Fischer's lock-key
theory and was articulated by Cram [64]. In order to obtain high-affinity hosts, chemists
normally resort to macrocyclic structures that require very little conformational changes
to bind the guest, with the assumption that the cost of the conformational change during
the binding needs to be paid from the binding interactions. Foldamer-based hosts, of
course, deviate from this convention and, as described earlier, frequently experience
large-scale conformational changes during the binding. Interestingly, although a huge
number of rigid supramolecular receptors have been synthesized by chemists, the vast
majority of them give very poor binding affinity in comparison to foldamer-based protein
hosts [65]. Not surprisingly, some researchers in recent years began to question whether
chemists, in an effort to rigidify supramolecular hosts, have moved away from some key
elements of success [66-68].
Zhao and coworkers recently reported the naphthyl-dansyl functionalized dicarboxy-
lated oligocholate 14 [69]. Similar to 13 , the compound had a cooperative conformational
transition in methanol/EA mixtures and became fully unfolded in 15% methanol
(Figure 12.7a). Fluorescence titration revealed that its binding affinity for Zn 2þ was high-
est in 15% methanol (Figure 12.7b). The results suggested that the conformational change

8.4

(b)

140

(a)

8.2

120

8.0

100

7.8

80

7.6

60

40 7.4

20 7.2

0 7.0

0 5 10 15 20 25 30 0 5 10 15 20 25 30

% MeOH in EA % MeOH in EA

Figure 12.7 (a) Emission intensity of dansyl at 492 nm for 14 ( ~ ), 15 ( ^ ), and 16 ( & )in
MeOH/ EA mixtures. The high intensity of 14 in < 15% methanol came from the FRET in the
folded conformation. (b) Binding free energy between 14 and Zn(OAc) 2 in MeOH/ EA mix-
tures. Reprinted with permission from [ref 69] Copyright 2011 American Chemical Society.