Chemistry Reference
In-Depth Information
photooxidation of DNA bases, photobinding metal polyazine chromophores to DNA
and photocleavage of the DNA backbone by the excited inorganic chromophore.
These studies show both the complexity of the interactions of metal complexes with
DNA in the excited state and the potential promise of these complexes in PDT.
The excited states of metal polyazine complexes are easily tuned by modifi ca-
tion of the ligand environment, as is tuning of ground state interactions of these
systems with DNA. Metal complexes that associate with DNA to a greater extent
prior to photolysis tend to have enhanced effi ciency of DNA photomodifi cation.
Given the typically low concentration of DNA, metal complex- DNA interactions
are key to photoreaction effi ciency. Systems incorporating extended planar, aro-
matic, polyazine ligands or systems containing lipophilic polyazine ligands generally
interact strongly with DNA.
The studies of metal complexes and their light activated modifi cation of DNA
show the promise of metal complexes in this forum. The studies summarized herein
illustrate examples of a variety of photoreactions with DNA. Many systems react
with DNA by yet to be understood mechanisms.
Surprisingly few studies of platinum group metal polyazine complexes with
cells have been undertaken and it is clear that much is to be learned in this forum.
The utility of metal complexes as chromophores in photoinitiated cell killing schemes
remains clear. The photochemical mechanisms of platinum group metal polyazine
complexes leading to cell death have yet to be explored. The more detailed studies
of DNA photomodifi cation noted for these systems suggest this as a possible mecha-
nism of cell photokilling. Cellular uptake mechanisms of metal polyazine complexes
are currently being investigated to understand the relationship between ligand
lipophilicity and uptake. While Barton and coworkers show that rational design
strategies can be used to develop platinum group metal polyazine complexes which
readily enter cells, many surprises are being uncovered. Studies of multinuclear
polyazine complexes illustrate the utility of this class of photosensitizer in future
photodynamic therapy schemes. The low dark toxicity and high light activated cell
killing makes these supramolecular systems particularly promising to develop new,
potent PDT agents. Continuing studies within the fi eld of platinum group metal
polyazine complexes as PDT agents, will ultimately lead to their clinical use in the
treatment of cancer.
Acknowledgements
Special thanks to Prof. Brenda S.J. Winkel for her frequent questions, discussions
and collaborations on studies of mixed-metal supramolecules and their photochem-
istry with DNA. The authors would especially like to thank the National Science
Foundation for their generous support of this work (CHE-0408445). The authors
thank Theralase, Inc. for continued collaboration to investigate the PDT action of
supramolecular complexes. The authors would also like to thank Dr Shamindri M.
Arachchige, Dr Krishnan Rangan, Avijita Jain, Samantha Hopkins and Anne-Marie
C. Overstreet for help with this chapter.
