Chemistry Reference
In-Depth Information
8.5 Cell Studies with Metal Complexes
Cellular uptake and photoinitiated cell death is indicated for several metal polyazine-
based light absorbers. Given the short timeframe of this research effort, this is a
very promising result, with no strong understanding of means to design systems that
will transport into the nucleus. Several groups indicate uptake of the metal complex
in the cell to be a function of the ancillary ligands lipophilicity.
1,66,79
Metal complexes
representing different constructs outlined in preceding sections are promising as
PDT agents. Surprisingly few cell studies with Ru, Os or Rh polyazine chromophores
have been performed, given the breadth of knowledge of the photochemistry of these
complexes with DNA. Cell studies of some Ru, Os and Rh polyazine complexes
have revealed their excellent phototoxicity and minimal dark toxicity.
33,65,66,79 - 84
Table
8.2 is a synopsis of the cell studies with transition metal polyazine complexes.
Table 8.2
Transition metal polyazine complexes used in cell studies with applications in PDT
Complex
a
Description of Interaction
Ref.
[Ru(bpy)
3
]Cl
2
and
[Ru(phen)
3
]Cl
2
• Cellular uptake following photolysis
• Phototoxic at concentrations
80
>
10
−
4
M
[(bpy)
2
Ru(ddz)]Cl
2
• Selective uptake and luminescence
enhancement by nonviable cells
• Cell photokilling not investigated
81
[(TL)
2
Ru(dppz)]Cl
2
TL = bpy,
phen, mcmb, Ph
2
phen
• Cellular uptake as a function of lipophilicity,
size and overall charge
• Faster uptake for complexes with lipophilic
ligands (e.g. TL = Ph
2
phen)
• Cell photokilling not investigated
79
cis
-[(TL)
2
RhCl
2
]Cl
TL = phen, 5,6-Me
2
phen,
Me
4
phen, Ph
2
phen
• Uptake investigated as function of lipophilicity
• Uptake observed only for TL = Me
4
phen
• Phototoxic to tumour cell lines at 55
66
µ
M and
irradiation with
>
400 nm light
cis
-[(phen)(dppz)RhCl
2
]Cl
• Penetrates cellular membranes and viral coats
• Phototoxic to tumour cells at 40
65
µ
M and
irradiation with 311 nm light
• Deactivates viral DNA within intact virus
[(phen)(chrysi)Rh(dmb-
(arg)
8
-DYE)](O
2
CCF
3
)
11
• Metal complex with octa(arginine) tail and
fl uorescent dye
• Rapid uptake observed at 5
82
M
• Cell photokilling not investigated
µ
cis
-[Rh
2
(
-O
2
CMe)
2
(dppz)
(bpy)](O
2
CMe)
2
µ
• Dark toxicity reported LC
50
= 208
µ
M
33,83
• Phototoxic LC
50
= 44
µ
M with 30 min, 400-
700 nm irradiation
[{(bpy)
2
M(dpp)}
2
RhCl
2
]Cl
5
,
M = Ru or Os
84
• No dark toxicity observed (tested up to 120
µ
M)
• Phototoxic at 5
µ
M, with 4 min , 400-1000 nm
irradiation
a
bpy = 2,2
′
-bipyridine; phen = 1,10-phenanthroline; mcmb = 4-carboxy-4
′
-methyl-2,2
′
-bipyridine, Ph
2
phen = 4,7-
diphenyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2
-c]phenazine; 5,6-Me2phen = 5,6-dimethyl-1,10-phenan-
throline; Me4phen = 3,4,7,8-tertramethyl-1,10-phenanthroline; chrysi =
a
-chrysenequinone diimine; ddz = dibenzo
[h,j]dipyrido[3,2-a:2
′
,3
′
′
,3
′
-c]phenazine; dpp = 2,3-bis(2-pyridyl)pyrazine.
