Chemistry Reference
In-Depth Information
precursors gave only 1-10% yields. Regioisomerically pure phthalocyanines
50
-
52
were prepared by condensation of the corresponding boronated phthalonitrile with
30-fold excess of 1,2-dicyanobenzene, to produce the A
3
B-type carboranylphthalo-
cyanines as the only product in addition to the symmetric A
4
-type phthalocyanine,
which was removed by filtration [
86
,
87
]. The carborane-containing phthalonitriles were
prepared by nucleophilic ring opening of zwitterionic [3,3
0
-Co(8-C
4
H
8
O
2
-1,2-C
2
B
9
H
10
)
(1
0
,2
0
-C
2
B
9
H
11
)] by phenoxy- or pyridyl-functionalized phthalonitriles under basic
conditions.
4 Conclusions and Outlook
Over 100 boron-containing tetrapyrrolic macrocycles have been synthesized for
application in BNCT following two main methodologies: by total synthesis from
boronated monomeric precursors or from functionalization of a pre-formed
macrocycle. However, only a few of these boronated macrocycles have been
evaluated in preclinical biological investigations. The early reported carboranyl-
porphyrins BOPP and CuTCPH were shown to deliver therapeutic amounts of
boron to tumor-bearing mice, with high tumor-to-blood and tumor-to-brain boron
concentration ratios [
19
,
34
,
35
,
39
-
41
,
88
-
94
]. Several other boronated
macrocycles containing hydrolytically stable carbon-carbon linkages between the
macrocycle and carborane groups (e.g., H
2
TCP and H
2
DCP) and/or higher amount
of boron by weight than BOPP and CuTCPH (e.g., H
2
OCP) were also shown to
have low mice toxicity, and to deliver therapeutic amounts of boron to tumor-
bearing mice [
47
,
54
,
60
,
65
]. All other boronated porphyrin derivatives have
only been evaluated in preliminary cellular studies, and their in vivo biological
properties are still unknown.
