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by its own accessibility of the phosphorescent core to oxygen, bringing about
multitude of constants k
q
. As a result, phosphorescence decays of polyglutamic
probes in the blood are by default nonsingle exponential. The only rigorous way to
describe these decays is to carry out phosphorescence lifetime distribution analysis,
such as that based on the maximum entropy method (MEM) [74]. However, for the
purpose of oxygenmeasurements it is appropriate to use “apparent” lifetimes, which
are theweighted averages derived fromunderlying lifetime distributions. Averaging
canbedone,forexample,byfittinganonsingle-exponential decay using two-,
three- or higher exponential models and deriving the intensity-weighted average
lifetimes. Alternatively, one can use single-exponential fitting, which would
generate poorer residuals, but would be more robust due to the fewer number of
fitting parameters. Single-exponential fitting in this regard can be considered an
alternative form of averaging.
The drawbacks associated with use of dendritic polyglutamic porphyrins clearly
show that probes with albumin-independent phosphorescence lifetimes and oxygen
quenching constants would greatly simplify data analysis and broaden applicability of
the method (e.g., make possible measurements in albumin-free environments).
Although polyglutamic dendrimers in the end were incapable of providing sufficient
shielding to porphyrins, experiments performed with these molecules implied that the
composition of the dendritic matrix is at least as important for shielding as the
dendrimer size. This result served as a starting point for more systematic studies of
the interplay between the dendrimer composition, size, and encapsulating efficiency,
as measured by oxygen diffusion and quenching of phosphorescence.
14.6 INFLUENCE OF SIZE AND COMPOSITION OF DENDRITIC
MATRIX ON OXYGEN SHIELDING EFFICIENCY
In order to determine which dendrimers provide optimal attenuation of oxygen
quenching of porphyrin phosphorescence a study was performed [75], which
involved three types of porphyrin dendrimers: Fr
echet-type poly(aryl ethers) [76],
Newkome-type poly(ether amides) [77,78], and polyglutamates [65] (Figure 14.8).
Fr
echet-type dendrimers (Fr) are composed of less polar monomers, and thus they
were assumed to be the most hydrophobic in the selected group. In addition, their
folding in aqueous environments was expected to be facilitated by
p
-
p
-stacking
interactions. Because of the same branching number (BN
¼
2) and close molecular
weights of the monomers, poly(aryl ethers) (MW
¼
105), and polyglutamates
(MW
112) exhibit essentially the same mass increase per dendritic generation.
Newkome poly(ether amides) (MW
¼
3), on the other hand, are similar to
polyglutamates in chemical composition, but have much larger mass increase per
generation. All three dendrimers are relatively flexible, and therefore substantial
conformational changes could be expected in solvents of different polarities.
Pd-meta-octahydroxyphenylporphyrin and Pd-meta-octacarboxyphenylporphyrin,
compatible with either Williamson (Fr) or peptide (Nw, Glu) chemistries, were used
as phosphorescent cores. The studies were performed in DMF, THF, and water. To
¼
285, BN
¼
