Chemistry - A European Journal
10.1002/chem.201902556
COMMUNICATION
reduced binding efficacy may be explained the increased steric
bulk of the guanidinium moiety of 33 compared to the smaller
ammonium residue of 31. When N-acetylated lysine methyl ester
phosphate residues being located at the tips of the tweezer, the
entry into the cavity of 11 is narrow compared to 1 and does not
offer enough space for sterically more demanding guests. Our
(
(
30) was titrated with 11, we observed very weak binding
results suggest that 11 represents
a
system that is
–
1
K
a
= 3.40 M ). This demonstrates the strong influence of charge,
complementary to previously reported molecular tweezers. The
highly modular synthesis of 11 allows for fast and easy
derivatization, a process that is currently ongoing in our lab.
but also sterics of the guest on the interactions between host and
guest, since the more accessible cavity of tweezer 1 has been
reported to allow for strong interaction with both 30 and 32 (see
Supporting Information). The low binding constant of weakly basic
Acknowledgements
–
1
a
histamine hydrochloride (35) and 11 (K = 121 M ) and histidine
–
1
This work was supported by the Swiss National Science
Foundation as part of the NCCR Molecular Systems Engineering
program. M.H. acknowledges Dr. Michael Pfeffer for HR-MS
analysis and Dr. Daniel Häussinger for support in NMR titration
experiments.
methyl ester (36) and 11 (K
the imidazole moiety predominantly not being protonated in the
phosphate buffer we used, rendering the material
a
= 21.2 M ) can be rationalized with
a
monoammonium species, which have already been shown to
bind to 11 only moderately. We did not observe binding of
histidine (37). Taking into account that additional steric bulk of a
carboxylate impairs the binding of lysine derivative 31 compared
to its parent diamine 17 and that histamine is a weak binder, these
results are in agreement with our expectations. We finally looked
into the possibility to employ 11 to bind biologically relevant
molecules. We therefore investigated the binding of both
Keywords: host-guest complexes • amines • molecular
recognition • molecular tweezers • supramolecular chemistry
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K
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M
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at pD = 4.2 and
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= 5.12•10 M–1 at pD = 10.2), leaving host-guest interaction
4
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large span of aliphatic and other sterically undemanding diamines
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factors: (1) The strong ionic interactions of protonated ammonium
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hydrogen-bonding dictates the binding properties. (2) Due to the
[
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