13 research outputs found
Guest-Host Chemistry with Dendrimers—Binding of Carboxylates in Aqueous Solution
<div><p>Recognition and binding of anions in water is difficult due to the ability of water molecules to form strong hydrogen bonds and to solvate the anions. The complexation of two different carboxylates with 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimers was studied in aqueous solution using NMR and ITC binding models. Sodium 2-naphthoate and sodium 3-hydroxy-2-naphthoate were chosen as carboxylate model compounds, since they carry structural similarities to many non-steroidal anti-inflammatory drugs and they possess only a limited number of functional groups, making them ideal to study the carboxylate-dendrimer interaction selectively. The binding stoichiometry for 3-hydroxy-2-naphthoate was found to be two strongly bound guest molecules per dendrimer and an additional 40 molecules with weak binding affinity. The NOESY NMR showed a clear binding correlation of sodium 3-hydroxy-2-naphthoate with the lyophilic dendrimer core, possibly with the two high affinity guest molecules. In comparison, sodium 2-naphthoate showed a weaker binding strength and had a stoichiometry of two guests per dendrimer with no additional weakly bound guests. This stronger dendrimer interaction with sodium 3-hydroxy-2-naphthoate is possibly a result of the additional interactions of the dendrimer with the extra hydroxyl group and an internal stabilization of the negative charge due to the hydroxyl group. These findings illustrate the potential of the G4 1-(4-carbomethoxy) pyrrolidone dendrimer to complex carboxylate guests in water and act as a possible carrier of such molecules.</p></div
The best fit obtained for the <sup>1</sup>H-NMR-titration of sodium 2-naphthoate into the PyrG4 dendrimer in aqueous solution.
<p>The calculated binding constant corresponds to K<sub><i>a</i></sub> = 5.35±0.7 M<sup>-1</sup> for <i>n</i> = 2 carboxylates.</p
ITC-binding curve of 3-hydroxy-2-naphthoate, showing the best fit.
<p>The ITC raw data was treated by blank subtraction (titration of guest into water).</p
Stacked <sup>1</sup>H-NMR spectra of different ratios of 3-hydroxy-2-naphthoate incubated with a 1 mM G4 1-(4-carbomethoxy) pyrrolidone dendrimer in D<sub>2</sub>O.
<p>Stacked <sup>1</sup>H-NMR spectra of different ratios of 3-hydroxy-2-naphthoate incubated with a 1 mM G4 1-(4-carbomethoxy) pyrrolidone dendrimer in D<sub>2</sub>O.</p
The two model guests illustrated within a G4 1-(4-carbomethoxy) pyrrolidone dendrimer.
<p>The two model guests illustrated within a G4 1-(4-carbomethoxy) pyrrolidone dendrimer.</p
2D-NOE-spectrum showing a significant correlation between sodium 3-hydroxy-2-naphthoate and the G4 1-(4-carbomethoxypyrrolidone) PAMAM-dendrimer.
<p>2D-NOE-spectrum showing a significant correlation between sodium 3-hydroxy-2-naphthoate and the G4 1-(4-carbomethoxypyrrolidone) PAMAM-dendrimer.</p
Photophysical Properties of Fluorescent Core Dendrimers Controlled by Size
A series
of different generation PAMAM dendrimers with sulforhodamine B covalently
attached to the dendrimer core was investigated regarding their optical
properties. Steady-state and time-resolved spectroscopic techniques
were used to determine the size influence of the dendrimers on the
photophysical behavior of the luminescent core. New blue emissive
species were formed as the generation increased from zero to four.
The growth of the dendritic branches resulted in a rise of fluorescence
quantum yield and fluorescence lifetime values. Rotational correlation
times were used to determine the hydrodynamic diameters of the fluorescent-core
dendrimers, and good accordance was found with the values previously
reported for unlabeled PAMAM dendrimers, which makes them potentially
suitable diagnostic tools for biomedical tracing
Toward Plasmonic Biosensors Functionalized by a Photoinduced Surface Reaction
We present a method for efficient
coupling of amine nucleophilic
molecules of choice to a nanostructured gold surface via photoinduced
surface chemistry. The method is based on photoactive self-assembled
monolayers and can be used to functionalize localized surface plasmon
resonance (LSPR) based biosensors with biorecognition motifs while
reducing nonspecific binding via introduction of hydrophilic units.
The photoactive linker molecule, 5-bromo-7-nitroindoline, couples
nucleophilic molecules such as biotin ethylenediamine to a surface
when exposed to UV-light. The specific, noncovalent recognition between
biotin and streptavidin is used for demonstration of a simple biorecognition
assay based on the LSPR sensing principle. By doing so, one can envision
that the binding of any streptavidin fusion protein, being attached
to specific spots at the gold surface, is monitored by an LSPR peak
shift. Since the surface functionalization is based on a photoinduced
reaction, this method can be used to functionalize the surface in
a local and site-specific way, and biomedical applications such as
drug-screening platforms, microarrays, solid support protein synthesis,
and even single molecule experiments can be envisioned
Complexes of Indomethacin with 4‑Carbomethoxy-pyrrolidone PAMAM Dendrimers Show Improved Anti-inflammatory Properties and Temperature-Dependent Binding and Release Profile
COX-2
inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs)
are the most common treatment for chronic inflammatory diseases like
arthritis and atherosclerosis. However, they are associated with severe
side effects such as cardiovascular events or stomach bleeding, due
to coinhibition of other enzymes (COX1) and off-target accumulation.
PAMAM dendrimers can solubilize lipophilic drugs and increase their
circulation time; furthermore, PAMAM dendrimers seem to have some
accumulation in inflammatory sides. Three different generations of
4-carbomethoxypyrrolidone (Pyr) surface-modified PAMAM dendrimers
were complexed with the NSAID drug indomethacin, and their in-solution
thermodynamic profiles were studied by means of NMR experiments. The
binding stoichiometry was found dependent on solvent system and dendrimer
generation. Larger dendrimers (G3-Pyr) were found to bind indomethacin
through entropy driven binding mode, while G1-Pyr and G2-Pyr expressed
an enthalpy driven complex formation, which means that the binding
constants have a generational temperature dependency. G1/2-Pyr showed
reduced binding with increasing temperature, which could be important
for drug release at inflammatory sites, which have, in general, elevated
temperatures. In vitro studies elucidated that the indomethacin drug
remained its activity when delivered as a dendrimer–indomethacin
complex. A slight reduction in toxicity profile was noticed for G2/G3-Pyr-indomethacin
dendrimers. Both free indomethacin and dendrimer–indomethacin
complex inhibited a variety of pro-inflammatory cytokines in LPS treated
cells. However, only the indo–dendrimer complexes showed a
significant reduction of IL-1β in LPS-treated THP-1 cells, which
was not present in the control with free indomethacin
Copper(II) Complexes with 4‑Carbomethoxypyrrolidone Functionalized PAMAM-Dendrimers: An EPR Study
The
internal flexibility and interacting ability of PAMAM-dendrimers
having 4-carbomethoxypyrrolidone-groups as surface groups (termed
Gn-Pyr), which may be useful for biomedical purposes, and ion traps
were investigated by analyzing the EPR spectra of their copper(II)
complexes. Increasing amounts (with respect to the Pyr groups) of
copper(II) gave rise to different signals constituting the EPR spectra
at room and low temperature corresponding to different coordinations
of Cu<sup>2+</sup> inside and outside the dendrimers. At low Cu<sup>2+</sup> concentrations, CuN<sub>4</sub> coordination involving the
DAB core is preferential for G3- and G5-Pyr, while G4-Pyr shows a
CuN<sub>3</sub>O coordination. CuN<sub>2</sub>O<sub>2</sub> coordination
into the external dendrimer layer was also contributing to G3- and
G4-Pyr spectra. The structures of the proposed copper–dendrimer
complexes were also shown. G4-Pyr displays unusual binding ability
toward Cu(II) ions. Mainly the remarkably low toxicity shown by G4-Pyr
and its peculiar binding ability leads to a potential use in biomedical
fields