Interaction between the Peroxide Adduct of Binuclear Iron(III) Complex
with (HPTP) Anion and the Sugar Moiety of Nucleosides
Satoshi Nishino2, Mami Kunitaa, Teruyuki Kobayashiu, Hideaki Matsushimab,
Tadashi Tokiib, and Yuzo Nishidaa’*
a Institute for Molecular Science, Okazaki 444-8585, Japan
b Department of Chemistry, Faculty of Engineering, Saga University, Saga 841, Japan
* Reprint requests to Y. Nishida. Fax: (+81) 564 55 5245. E-mail: yuzo@ims.ac.jp
Z. Naturforsch. 54 b, 1272-1276 (1999); received February 15, 1999
DNA Cleavage, Peroxide Adduct of Binuclear Iron(III), Interaction with Sugar moiety
We have in this study obtained the experimental evidence to suggest that the peroxide adduct
of binuclear iron(III) complex with H(HPTP) directly reacts with the sugar moiety of the
DNA chain, to cleave it; H(HPTP) denotes N,N.N',N'-tetrakis(2-pyridylmethyl)-l,3-diamino-
2 -propanol.
Introduction
>CH2-)2NCH2CHCH2N(-CH2- ( ^ ) 2
H(HPTP)
Bleomycins(BLM) are a group of antitumor an-
tibiotics, first isolated by Umezawa in 1966 [1].
These compounds are used clinically in the treat-
ment for head and neck cancer, testicular cancer,
and squamous carcinomas [2]; their cytotocity is
thought to be related to their ability to bind and
tdegrade double-stranded DNA [3]. Extensive ef-
forts by numerous investigators in the past decade
have provided much information about the prod-
ucts during BLM-mediated degradation of DNA
and the chemistry of their formations [4, 5]. In-
cubation of BLM with Fe2+ and O2 yields a mixture
of ferric-BLM and “activated BLM”, a species re-
cently shown to contain BLM-ferric-peroxide by
electrospray mass spectroscopy [6], However, the
discussion how the metal-peroxide adduct cleaves
DNA is scarce [7], and also there’s no evidence to
support that the peroxide adduct reacts directly with
DNA [8]. In this study we will show clear evidence
that the peroxide adduct of a binuclear iron(III) re-
acts directly with DNA to degrade it.
Preparation of the metal compounds: The ligand,
H(HPTP), used in this study was obtained according to the
literature method [9]. The methanol solution of H(HPTP)
was mixed with a methanolic solution of ferric chloride
hexahydrate, to give a yellow powder.
Fe2 (HPTP)Cl4 FeCl4
Calcd C 35.84 H 3.23 N 9.29%,
Found C 35.81 H 3 .ll N 9.23%.
When the yellow powder (1.0 g) was recrystallized from
a methanol/acetonitrile (v/v = 1 / 1 ) solution containing
NaC1 0 4 monohydrate (1 . 0 g), orange prisms were ob-
tained.
Fe2 (HPTP)Cl4 C104
Calcd C 40.21 H 3.62 N 10.42%,
Found C 40.41 H 3.85 N 10.99%.
Crystal structure determination of compound 2 ■
CHjOH: An orange yellow prism having approximately
dimensions of 0.25 x 0.25 x 0.35 mm was mounted
on a glass fiber. All measurements were made on a
Rigaku AFC5S diffractometer with graphite monochro-
mated MoKa radiation and a 12 KW rotating anode gen-
Experim ental Section
Materials: DNA(calf-thymus, pBR322, 0x174) was erator at Saga University. Cell constants and an orien-
obtained from Wako Chemicals (Osaka). In this tation matrix for data collection, obtained from a least-
study, the binuclear iron(III) complex with p-a\k-
squares refinement using the setting angles of 25 carefully
centered reflections in the range 10.00 < 29 < 22.04°,
oxo bridge, Fe2 (HPTP)(OH)(NO;0 2 (C1 0 4 ) 2 (1 ) and Fe2 -
(HPTP)Cl4 C1 0 4 (2) were used, where H(HPTP) repre- corresponded to a monoclinic cell dimension with a =
sents N.N,N',N'-tetrakis(2-pyridylmethyl)-1,3-diamino-
2-propanol [9].
12.882(6), b = 15.376(2), c = 18.488(3) Ä, ß = 106.19(2)°,
V = 3517(2) A3, space group P21/c, Z = 4, F. W. = 838.56.
K
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