Chemistry Reference
In-Depth Information
dendrimers. The substrate loading is often more predictable and superior with
covalent reactions. Some purifications could also be more easily envisaged. Depend-
ing on the applications, the hydrophilicity/hydrophobicity, wetting properties, and the
water-solubilitywill often have to be controlled, depending on the substrate. A surface
functionalization by a PEGylation or the use of other hydrophilic linkers, combined to
the proper dendritic scaffold, might ensure a final water-soluble dendrimer-conjugate.
Overall, both approaches are complementary. The supramolecular approach looks
simpler at a first glance but the instability and the less predictable thermodynamic
supramolecular assembly might be discouraging compared to the covalent approach.
On the other hand, the covalent approach suffers from further synthetic efforts but
might provide a better control of the resulting effects. A chemical surface modifi-
cation renders the supramolecular approach at a similar level in terms of synthetic
efforts and purifications.
13.2.3 Some Parameters for Degradability (In Vitro)
This section will mainly focus on the hydrolytic degradability of dendrimers by
chemical, enzymatic means, or by using catalytic antibodies, but not via biodegra-
dation, which is directly related to the metabolism operating in living organisms.
There are a few reports on the stability and the degradation of dendrimers in life
sciences, including some studies of their metabolism and their biodegradation using
radioactive markers, and some novel imaging techniques using near-infrared nanop-
robes conjugated to dendritic aliphatic polyesters [107]. Additionally, most often this
section will not focus on a common deprotection or protection scheme used in
dendrimer synthesis, as some examples of degradation.
13.2.3.1 Stimulus or Triggers Up to the present, the degradation of dendrimers
has been initiated by common stimulus for breaking chemical bonds: (a) pH variation,
(b) enzymes, (c) catalytic antibodies, (d) light (single or double photon [108]
absorption), and various reactions with specific reagents. They comprise some
metal-mediated, redox, and thermal reactions. It is anticipated that any selective
and modern activation methods for cleaving a covalent bond could be useful,
especially if they are chemoselective and mild. Only recently, new dendrimers
preparations employed ultrasounds and microwaves [109,110]. Degradation using
those “nonconventional activation techniques” to voluntarily cleave or degrade
dendrimers are presently rare in the literature.
Hydrolysis bymeans of a pH variation or by the enzymatic uses of a depolymerase,
an esterase, a lipase, and a protease were among the first reports in the literature for
cleaving some monodisperse, discrete dendrimers [54]. Well before its time in
dendrimer chemistry, this report also described the first enzymatic degradations in
the literature and it clearly indicated that ester functions were adequate for such
enzymatic cleavages (as it was known for some degradable polyesters). Some
dendritic moieties could find their way to an enzymatic catalytic site in spite of
their peculiar degree of branching, their steric hindrance and their globular topology
(Scheme 13.3).
