Chemistry Reference
In-Depth Information
action, have low systemic toxicity and are eliminated rapidly from the body. The red
to NIR region of the spectrum (650-850 nm) is the light that has the greatest depth
of penetration in human tissue and is known as the 'therapeutic window'. Potent
light absorbers with moderately long-lived and reactive electronic excited states are
of particular interest. Chromophores with long-lived electronic excited states have
a high probability of approach to a substrate during the excited state lifetime. Ironi-
cally, excited-state energy and lifetime often are inversely related, with longer wave-
length light absorbers having short-lived excited states.
16
Some current PDT agents
show some cytospecifi city, accumulating in tumour cells and enhancing the photo-
sensitizer ' s PDT function.
14
Uptake of the PDT agent is often complicated and is
impacted by the size of the chromophore, its charge and its lipophilicity. Chromo-
phore size, charge and lipophilicity are important characteristics to consider in the
design of PDT agents for elimination from the body. PDT agents that have hydro-
phobic architectures are retained for long periods within the body, leading to pro-
longed patient photosensitivity.
15
Inorganic Complexes as PDT Agents
Current PDT treatments employ organic chromophores as photosensitizers, but
inorganic chromophores show great promise as PDT agents.
1,8
The fi rst approved
PDT agent was a hematoporphyrin derivative, Photofrin
®
(Figure 8.1 ). Other
photosensitizers have been approved, all of which are based on organic con-
structs.
14
PDT has not gained widespread clinical use, owing in part to the newness
of it as a therapy. In addition, the stigma of heavy-metal-containing compounds has
led to limited use of these promising species as PDT agents. Two metal-containing
photosensitizers are in clinical trials, metoxifi n lutetium and tin ethyl etiopurpurin.
Transition - metal - centred complexes with porphyrin, phthalocyanine, naphthalo-
cyanine or polypyridine-type ligands have interesting ES properties, making them
good targets for future therapies. This chapter will focus on inorganic systems with
excited state properties and bioactivity that makes them of interest as future PDT
agents.
8.1.4 DNA and PDT Action
Deoxyribonucleic acid (DNA) is a natural supramolecule with complex secondary
and tertiary structure whose integrity is central to the functioning of a cell (Figure
8.2). The importance of DNA to cellular function has directed research focus on
transition metal complexes as potential PDT agents based on their ES reactions
with DNA.
2
Several structures of DNA have been reported with B-form DNA being
the most prominent. A single turn of the B-form double helix is ca. 12 nm in length
and averages 10.4 p - stacked base pairs.
17
Two hydrophobic grooves run along the
surface of the DNA molecule. The major groove is broad and shallow, and the minor
groove is narrow and deep, both lined by the sugar phosphate backbone, giving
DNA its polyanionic character. These structural features can be used in the rational
design of DNA photomodifi cation agents.
