Biomedical Engineering Reference
In-Depth Information
N H 2
O
N
N
7
H 2 N
O
air
water
air-water interface
HN
10
18
Nucleotide
Fig. 6 The amphiphilic receptor 18 combines a long hydrophobic chain with a positively charged
guanidinium headgroup. At the air-water interface the positively charged guanidinium moieties
point towards the aqueous phase while the hydrophobic part points towards the air
In a similar approach Schmidtchen developed the tweezer 17, depicted in Fig. 5
[ 10 ]. Two chiral, bicyclic guanidinium moieties were connected via an aromatic
template. With the help of NMR titrations in water a very high binding constant of
10 6 M 1 to TMP could be observed, which was explained by a perfect
preorganization of the two guanidine units perpendicular to each other. This way
their geometry is perfectly matched to bind to the tetrahedral phosphate anion via
two hydrogen bonded salt bridges. Once more, preorganization and structural
complementarity proved to be the key to obtaining high affinity. For phosphate
binding, especially ditopic receptors with two anion binding groups seem to be
perfectly suitable.
The most successful approach towards guanidinium-based nucleotide recogni-
tion so far was Kunitake's receptor 18, shown in Fig. 6 [ 11 ]. By attaching a long,
lipophilic chain to a positively charged guanidinium head group, amphiphilic host
systems were obtained which were able to form micelles or bilayers in aqueous
systems. The binding properties towards adenine-based nucleotides were
characterized via ultrafiltration. With 2
10 7 M 1 being the highest binding
constant that was observed at an air-water interface in buffered water at pH 7 for
ATP, AMP was bound more weakly by one order of magnitude. The results of this
approach stress the importance of the microenvironment on binding events.
Kunitake's system is actually a simple guanidinium moiety which is set into a
defined microenvironment with the help of a long amphiphilic side chain, yet very
good binding constants could be achieved this way.
1.3 Calixarene- and Cyclodextrin-Based Receptors
The focus of most of the above-mentioned nucleotide receptors clearly lies within
charge-charge interactions to their substrate, sometimes accompanied by stacking
between the nucleobase and one or more aromatic moieties of the host systems.
While
-stacking is a powerful tool for molecular recognition, especially in aque-
ous media, it is not the only possible way to utilize non-covalent interactions in
water. The following examples put more focus on hydrophobic interactions, which
may contribute substantial amounts to the Gibbs free energy in water.
Diederich, for example, made use of a bowl-shaped calixarene with a resorcin[4]
arene scaffold and four phenylamidinium groups at the upper rim for his nucleotide
receptor 19 (Fig. 7 )[ 12 ]. Calixarenes form hydrophobic cavities in aqueous media
p
Search WWH ::




Custom Search