Post on 03-Jan-2016
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Welcome toJacobs University
Bremen
Presenter Name | Meeting | Date
Boron clusters as boron carriers for BNCT:
Possibilities and problems
Detlef Gabel
Jacobs University Bremen
2-
1-
1-
B12H122- C2B10H12 CB11H12
1- metalla-bis(dicarbollide)
C2B10H12 C2B10H12o-carborane m-carborane p-carborane
Time (min)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Flu
ores
cenc
e In
tens
ity (
norm
aliz
ed)
0
20
40
60
80
100
120
no BSH1 mM BSH3 mM BSH6 mM BSH12 mM BSH23 mM BSH30 mM BSH
Boron clusters puncture lipid membranes
1 2 08 04 00T im e (s)
-1 0 0 0
-5 0 0
0
23 41
Curr
ent (
pA)
1 2 08 04 00T im e (s )
23 41
13 14 15 16 17
0.25 μM B12I12 -100mV constant
Boron cluster compounds can be
enzyme inhibitors and
receptor ligands
NH
SO
O NH2
Brynda et al., Angew. Chem. Int. Ed. 51, 13760–13763, 2013
compound CA IX (µM)
o 0.38
m 1.12
nido 5.09
CB11 2.20
Carbonic Anhydrase IX
N NH
O N
O
Lee et al., J. Med. Chem. 2012, 55, 7290−7294
Inhibitor of nicotinamide phosphoribosyltranferase
N NH
O
compound A549 DLD1 T47D
FK866 1.62 3.14 3.20
o 0.92 1.69 1.29
m 0.41 0.31 0.32
p 0.99 2.20 0.58
Inhibition of cell growthIC50 (nM)
N
O
O
O
O
N
Cl
O
O
O
O
compound COX1 COX2
indomethacin methyl ester >25 0.250
o 12.8 0.084
m >25 >25
p >25 >25
Scholz et al., Bioorg Med Chem 20, 4830–4837, 2012
IC50 values of cyclic oxygenases(µM)
indomethacin methyl ester
Fan et al, J Chromatogr A 1256, 98, 2012
0
10
20
30
40
SilicaSephadex G50Sepharose
SuperdexEPC
capacity factor
Karki et al., Inorg Chem 51, 4894, 2012
Karki et al., Inorg Chem 51, 4894, 2012
Karki et al., Inorg Chem 51, 4894, 2012
Karki et al., Inorg Chem 51, 4894, 2012
Dihydrogen bonds between dodecaborate and water
Ural, Assaf, Nau
γ-Cyclodextrin
Ural, Assaf, Nau
Ural, Assaf, Nau
Boron Cluster Volume Å3
K M-1 (x103)
Na2B12H12 152 2.03
Na2B12Cl12 333 14.3 Na2B12Br12 416 956 Na2B12I12 520 66.8
Na2B12H11SH ~152 7.80
Na2B12H11OH ~152 0.618 NaB12H11NH3 ~152 1.70 NaB12I11NH3 ~520 123
Association constants of boron clusters with γ-cyclodextrin
Ural, Assaf, Nau
Boron clusters can interact strongly with lipidsproteinscarbohydrates
Interactions cannot be predicted easily
Unwanted behavior cannot be excluded
Can one use the interaction for other purposes?
In vitro and in vivo testing appears necessary