Two new bleomycin analogues, 2-[((2-(4-imidazolyl)ethyl)amino)carbonyl]-6-[((2-amino-2-methylpropyl)amino)methyl]pyridine =
L3 and 2-[((2-(4-imidazolyl)ethyl)amino)carbonyl]-6-[((2-amino-1,1,2-trimethylpropyl)amino)methyl]pyridine =
L4, were synthesized in order to create air-stable ligands of their Cu
I (and Fe
II) complexes.The protonation constants (log
Kn) of the ligands at 25
C and
I = 0.1 M NaNO
3 were 9.9, 6.9, and 5.2 for
L3and 10.0, 6.7, and 3.9 for
L4. The complexation of the triprotonated
L3 and
L4 with Cu
II started at pH < 5 toyield 4-coordinate [Cu
II(H
-1L)·H
+]
2+ complexes,
4 and
6, respectively, followed by formation of square-pyramidal[Cu
II(H
-1L)]
+ complexes,
5 and
7, with p
Ka values of 5.6 for
5 and 5.9 for
7. The complexation constants, log
KCuIIH-1L, were 8.9 for [Cu
II(H
-1L
3)]
+,
5, and 8.6 for [Cu
II(H
-1L
4)]
+,
7, respectively. The structures of[Cu
II(H
-1L
3)]ClO
4 (
5·ClO
4) and [Cu
II(H
-1L
4)]BF
4 (
7·BF
4) were determined by X-ray crystallography. Crystaldata for
5·ClO
4: monoclinic, space group
P2
1/
n (No. 14),
a = 13.978(6) Å,
b = 8.103(3) Å,
c = 18.037(5) Å,
= 98.61(3)
,
V = 2019(1) Å
3,
Z = 4,
R = 0.053, and
Rw = 0.044 for 2996 [
I > 3
(
I)] reflections. Crystal datafor
7·BF
4: monoclinic, space group
P2
1/
n (No. 14),
a = 16.092 (4) Å,
b = 7.974(4) Å,
c = 16.819(2) Å,
=99.64(1)
,
V = 2127(1) Å
3,
Z = 4,
R = 0.040, and
Rw = 0.025 for 1633 [
I > 4
(
I)] reflections. The coordinationgeometry around the copper was a distorted square-pyramid in
5, while that of
7 was the intermediate betweena trigonal-bipyramid and a square-pyramid. The distortion is influenced strongly by the number of the methylgroup. The EPR spectral data for both copper(II) complexes were consistent with the retention of the solid-statestructure in frozen DMF/MeOH (1:1) solution at 77 K. The visible absorption spectra of 10% DMF/aqueoussolutions (pH 9.5) of
5 and
7 at
I = 0.1 M NaNO
3 showed absorption maxima at 646 nm with a shoulder at ca.900 nm for
5 and at 658 and 888 nm for
7. The red-shift of
7 by ca. 12 nm relative to
5 reflects the distortiontoward the trigonal-bipyramidal geometry of
7 in solution. Both complexes displayed irreversible redox behaviorin DMF at
I = 0.1 M tetra(
n-butyl)ammonium tetrafluoroborate. The anodic and cathodic peak potentials obtainedby cyclic voltammetry for
5 and
7 were -0.14 and -0.76 V for
5 and -0.17 and -0.80 for
7 vs Ag/AgCl. Thecathodic potentials of copper(II) complexes were shifted toward the anodic direction by ca. 20-60 mV comparedto the nonsubstituted 5-coordinate, [Cu
II(H
-1L
1)]
+ complex,
16 (-0.82 V vs Ag/AgCl). The Cu
I complexes (
9and
10) are air-oxidized to the corresponding Cu
II complexes,
5 and
7, respectively.