Metalloproteins and Metallopeptides –Natural Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 14

CONH 2

CONH 2

H

N

N H

2

N N O S S

H

O

O O

H

N

H 2 N H

N

O

O

N

H

H OH

R

N

O

OH

OH

H

O

O

H O

OH

O

H O

O

OH

O N H 2

( 1 )

Blm can bind various metal ions [92], including Mn 2þ [93], Fe 2þ/3þ [94], Co 2þ/3þ [95],
Ni 2þ/3þ [96,97], Cu þ/2þ [98,99], Zn 2þ [98], Cd 2þ [100], Ga 3þ [101], and Ru 2þ [102] as
well as the radioactive 105 Rh for radiotherapy [103], changing the conformation of the
molecule from a supposedly more extended form ( 1 ) to a more compact form (Figure 1.11,
green structure). Metallo-Blm has a distorted octahedral geometry with coordinated imid-
azole, pyrimidine, amines of b-aminoalamine, the amide nitrogen of b-hydroxyhistidine,
and possibly the amide group of a- D -mannose, as shown by optical, NMR, EPR, and elec-
tron spin-echo envelope modulation (ESEEM) spectroscopic methods, crystallography,
and chemical modeling [104-107]. This leaves an open or exchangeable site for O 2 or
peroxo binding. Similar coordination chemistry was also suggested for Zn 2þ -Blm from 2-
D NMR [108], however excluding carbamoyl binding. The binding of Co 2þ -Blm to DNA
via the bithiazole rings does not influence the metal coordination, whereas the binding of
O 2 -Co-Blm affects the bound O 2 where the unpaired electron resides [109].
Low-spin diamagnetic Co 3þ complexes of Blm and analogues have structures similar
to Zn-Blm based on 2-D NMR spectroscopy, except the axial ligands [110,111]. The
structures of (DNA) 2 -Co 3þ -Blm and (DNA) 2 -(HOO)Co 3þ -Blm ternary complexes show
further structural changes upon DNA binding (Figure 1.11) [110,112]. The metal-binding
moiety is located in the minor groove of (DNA) 2 with the bithiazole rings intercalated into
the DNA double helix, rendering the bound peroxide close to the 4 0 -H of the scissile
ribose (

3A ). Conversely, the bithiazole is in the minor groove in Zn 2þ -Blm-DNA [113].
Nevertheless, intercalation of bithiazole may not be necessary for DNA cleavage since
DNA cleavage by Fe-Blm is similarly effective compared to its derivative with the bithia-
zole tethered to a porous glass bead [114]. Fe 3þ -Blm becomes low-spin (g

<

2.41, 2.18,
1.89) with a bound hydroxide at slightly alkaline conditions [115,116]. O 2 binds to Fe 2þ -
Blm to afford a superoxide O 2 -Fe 3þ -Blm complex based on its 57 Fe M

¼

ossbauer spec-
trum [117] which can afford an active HOO -Fe-Blm complex toward DNA cleavage
[11b]. The paramagnetic Fe 2þ -Blm (S

€

¼ 2) with distance-dependent fast relaxing