inorganic chemistry

delay observed with H 2 TClPBOH illustrates the success of the
design of a sensitizer for PDT from spectroscopic, photochemical,
and biological principles.

VI. Conclusions

Porphyrin derivatives present a variety of photochemical pro-
perties that have been much explored to obtain better sensitizers
for the PDT of cancer.Table VIIIsummarizes some of the more
relevant factors that should be considered in the design better
photosensitizers for PDT and relates them to structural
modifications. Some of these factors are contradictory, and
improved photosensitizers are likely to emerge from the best bal-
ance between these factors. Free-base and palladium complexes
of hydroporphyrins rank among the best sensitizers presently
available. Bacteriochlorins are particularly interesting for their
intense absorption in the near infrared and were recently shown
to be sufficiently stable for PDT when electron-withdrawing
groups and/or steric protection are introduced in their molecular
structure. In addition to photogenerating singlet oxygen, bacteri-
ochlorins have sufficiently low oxidation potentials to generate

TABLE VIII

GUIDELINES TODESIGNBETTERPORPHYRIN-BASEDPHOTOSENSITIZERS FORPDT

Objective Guideline Limitation

lmaxat
720 – 900 nm

Reduced porphyrins (e.g.,

bacteriochlorin)

Oxidation potential

decreases and oxidative

degradation becomes

facile

Largee Distorted porphyrins (e.g.,
large groups atb-positions)
Stability Increase oxidation potential
(e.g., electron-withdrawing
substituents, Pd^2 þor In^3 þ
complexes)

Low-energy charge transfer

states promote

radiationless transitions

IncreaseFT Introduce heavy atoms in
phenyls atmeso-positions or
diamagnetic heavy metal
ions

Excessive heavy-atom effect

will reducetT

tT> 10 ms Avoid distortion of the
macrocycle, charge transfer
states, paramagnetic ions,
and excessive heavy-atom
effect
Generate O 2  Lower the oxidation potential Compromise with stability
Tumor
retention

Moderate lipophilicity Toxicity of i.v. formulation

228 LUIS G. ARNAUT