Download DNA Cleavage by Mono- and Polynuclear Metal Complexes

Salah S. Massoud
University of Louisiana at Lafayette
DNA Cleavage by Mono- and Polynuclear
Metal Complexes
In the search for the development of “new reactive small molecule catalysts” that are
inexpensive and efficiently hydrolyze the phosphodiester bonds of DNA, understanding the
factors that might affect the DNA cleavage is considered to be the key step in synthesizing
“efficient artificial nucleases” for DNA cleavage. Our group has focused on the synthesis and
characterization of a number of mononuclear cobalt(II) and copper(II) complexes containing
tripodal pyridyl ligands. These complexes were used to study the cleavage of DNA under the
physiological conditions in order to evaluate the factors that affect this process such as 1) the
nature of the chelate ring size, and the length of the pyridyl arms, 2) mononuclear vs. dinuclear,
3) the nature of the central metal ion, and 4) the steric environment around the central metal.
O
Base
O P O
O-
H
H
O
H
HH
O
O P O
O-
N4-C
Base
H
H
O
H
HH
O
O P O
O-
H
H
O
Base
H
HH
A variety of novel mononuclear and
polynuclear Cu(II) and Co(II) complexes have
been tested to establish the rapid selective
cleavage of the P-O bonds in DNA and in
phosphodiester compounds. Some of our
compounds were proven to act as very
efficient nucleases in the hydrolytic cleavage
of DNA. Attempts are made to enhance the
reactivity of the compounds by changing and
modifying the ligand skeleton attached to the
central metal ion.
Polynuclear Inorganic Compounds –
Molecular Magentism
We are also interested in the design and characterization of polynuclear inorganic molecules of
interesting magnetic properties. These molecules may utilize certain application in Material
Sciences and in the field of condensed matter physics.
Salah S. Massoud
The strategy of synthesizing these
compounds depends on the assembly of
paramagnetic metal ions (Co2+, Ni2+, Cu2+)
via bridging ligands such as pseudohalides
(N3-, NCS-, N(CN)2-), polycarboxylic acids
and benzenoid aromatic oxocarbon dianions
(squarate and croconates). The selected
bridging ligands allow a wide separation
between the metal centers (3-11 Å) and
hence the resulting complexes would
mediate different magnetic interactions.
Also, part of this study is to correlate the
structural parameters of the bridging
compounds (geometry around the central
metal ions, geometrical factor, the
intramolecular M2+···M2+ bond distances, the
M2+-X-M2+ torsion angles, the axial M2+-bond
distances) to their magnetic properties.
University of Louisiana at Lafayette
{[Cu2(mepy)2((µ1,1-N3)2(µ1,3-N3)]2+}n
Modeling Some Biological
Molecules
Modeling the active sites in biologically
important moleculses is another area of our
research interests. This includes the
dinuclear bridged peroxo 3d metal
complexes which exist in some coppermetalloproteins such as in blood dioxygen
carrying hemocyanins in arthopods and in
carbonic anhydrase metalloproteins. An
example of bridged peroxo-complex is
shown for Co(III) complex [Co2(DPA)2(µ
pzdc)(µ1,2-O2)]+. Fixation of atmospheric
CO2 by metal complexes, such as the
bridged-carbonato-Cu(II)-MeDPA complex
in [Cu3(MeDPA)3(µ3-CO3)(OClO3)3]ClO4.
[Co2(DPA)2(µ pzdc)(µ1,2-O2)]+ ion
Collaboration (beyond Lafayette)
Prof. F. Mautner (Graz University, Graz-Austria)
Prof. R. Vicente (University of Barcelona, Barcelona –Spain)
Prof. F. Meyer (Georg-August-Universität Göttingen, Göttingen-Germany)
Prof. M. Mikuriya (Kwansei Gakuin University, 2-1 Gakuen, Sanda-Japan)
Prof. R. Lalancette (Rutgers University, York, NJ USA)
Prof. G. Yee (Virginia Tech., Blacksburg, VA USA)
Dr. J. Grebowicz (University of Houston-Downtown, Houston, TX USA)
Prof. I. Bernal (University of Houston, Houston, TX USA)
Prof. H. Terenzi (Universidade Federal de Santa Catarina, Florianopolis sc Brazil)