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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