31P/13C-NMR Analysis of Dendritic Architectures
A R T I C L E S
groups can bind ureido-acetic acid guest molecules via elec-
trostatic interactions and hydrogen bonding. The electrostatic
interactions occur through an acid-base interaction between
the carboxylic acid functionality of the guest and a tertiary amine
of the dendrimer. Hydrogen bonding occurs between the urea-
groups of the guest and host and should direct complexation to
the periphery of the dendrimer. A major increase in binding
strength can be achieved by increasing the acid strength of the
guest molecules. This has been observed both in the gas phase25
and in chloroform,26,30 when the carboxylic acid group was
replaced with a phosphonic or sulfonic acid group.
dependent on the pH. In water, the 13C chemical shift of
carboxylic acids can shift over 5 ppm downfield when the acid
is deprotonated and the carboxylate salt is formed.49-53 For
phosphonic acids, both upfield and downfield shifts in 31P NMR
have been reported upon deprotonation.54-57 This inspired us
to use 13C NMR and 31P NMR as a tool to investigate the
binding of ureido-acetic acid and ureido-phosphonic acid type
guests to urea-adamantyl dendrimers in chloroform. To make
analysis easier and to prevent long measurement times, a 13C
label has been incorporated in the carbonyl group of the acid
functionality of the ureido-acetic acid guest molecules.
For solubility reasons, guest 2 and 3 were synthesized and
used. Complexation experiments of both guests have been
performed to several dendritic hosts (1a-1e) (Scheme 1), and
the experimental results in case of host 1e were fitted to get an
idea of the binding stoichiometry and the association constant.
Exchange experiments have been performed in which both guest
molecules were simultaneously added to the dendrimer host, to
investigate the difference in binding strength between guest 2
and 3 in more detail.
Although mass spectrometry and NMR spectroscopy have
given useful information about the binding of these types of
guests to dendrimers, specific information about the number of
guests that bind to the host, the binding strength between guest
and dendritic host and the exchange kinetics between free and
bound guest in solution remains difficult to obtain. Overlap of
the signals in 1H NMR of guest and host hampers the analysis
of several complexes. Ideally, we would like to have a general
analytical methodology to investigate the binding of any guest
to the dendrimer in any solvent. In this report, we present the
results obtained by making use of 13C NMR and 31P NMR next
Results
1
to H NMR to investigate the guest-host interactions of 13C
Covalent Synthesis. The starting material for the 13C label
in guest 2 was the commercially available 1-13C-glycine
(Scheme 2). Reaction with benzyl alcohol in toluene in the
presence of p-toluenesulfonic acid resulted in the benzyl ester
of 1-13C-glycine as the p-toluenesulfonic acid salt (4). A Dean-
Stark setup was used to azeotropically remove the water that is
formed during the reaction. As a starting material for the
oligoethylene glycol part of guest 2, 3,4,5-tri(tetraethyleneoxy)-
benzoic acid was used, which was synthesized according to a
described procedure.58 This acid was reacted with ethylchloro-
formate in THF with triethylamine to afford the mixed
anhydride. This mixture was added to a solution of sodium azide
in water, and extractions with dichloromethane resulted in the
acyl azide derivative. The acyl azide could subsequently be
converted to the isocyanate 7 via the Curtius rearrangement in
labeled carboxylic and 31P phosphonic acid containing guest
molecules in more detail. The principle of the methodology is
investigated in detail for the fifth generation dendrimer.
Designing the System. In an apolar aprotic solvent like
chloroform, an acid (HA) and a base (B) are usually in
equilibrium with a tight ion pair. The formed anion (A-) and
cation (BH+) are in close proximity of each other due to
electrostatic attraction and hydrogen bonding (eq 1), and it is
generally believed that no free ions are present in solution.31-48
It is known that both the 13C chemical shift of carboxylic
acids and the 31P chemical shift of phosphonic acids are strongly
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