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Synthesis and
Properties of Novel Phthalocyanine-based Photosensitizers for Photodynamic
Therapy
Sharman, Wesley 1
and van Lier, Johan1
Department of Radiobiology, Faculty of Medicine, University of Sherbrooke1
Abstract-
Phthalocyanines (Pcs) and their symmetrically substituted derivatives
have found extensive applications in an ever increasing number of wide-ranging
and diverse fields due to their unique physical, chemical and spectral
properties. Unsymmetrically substituted Pcs show improved properties
that increase their potential in a number of these fields including
photodynamic therapy (PDT). However, synthetic approaches towards these
Pcs are quite limited and often lead to a mixture of inseparable products.
The lower homologs of Pcs, boron subphthalocyanines (subPcs), have been
shown to act as a template in a ring expansion reaction with various
Pc precursors and allow for the synthesis of 3:1 unsymmetrically substituted
Pcs. Several novel subPcs have been synthesized and their spectral properties
examined. Boron subnapthalocyanines absorb at a much longer wavelength
than subPcs (around 660 nm) and their cone-shaped structure prevents
aggregation, making them potentially usefully for PDT. A series of these
compounds is currently being prepared and their properties are being
examined. On the other hand, halogenated subPcs exhibit ring expansions
under mild conditions and yield pure 3:1 asymmetric Pcs as demonstrated
by high resolution mass spectroscopy. Fluorinated Pcs have interesting
properties for PDT and a series of dodecafluorinated Pcs have been prepared
using this methodology and are undergoing in vitro examination. Iodinated
macrocycles, on the other hand, provide an important functional group
for the modification of the Pc periphery. Palladium-catalyzed reactions
can be used to add reactive and labile substituents to the Pc macrocycle,
increasing their potential utility in a number of applications. For
instance, palladium-catalyzed amination has been used to add hydrophilic
moieties to the Pc, leading to a series of water-soluble amphiphilic
cationic Pcs.
Keywords: phthalocyanines,
subphthalocyanines, photodynamic therapy, ring expansion reaction
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