THOMAS
C. STREKAS
INORGANIC/BIOCHEMISTRY
Ph.D. Princeton University (1974)
Our
recent research efforts have been directed toward the study of tris-chelates of
ruthenium(II) with bis-diimine ligands which induce binding to DNA via an
intercalative mode of interaction in which the chelated ligand interleaves
between adjacent base pairs within the double helical structure of the DNA.
This has been a collaborative effort with Dr. Dave Baker and his research group
of our department. The figure below shows one such complex, with the
intercalative ligand ppz directed toward the viewer.
Space-filling picture
of L-Ru(bpy)2(ppz)(+2)
with intercalative
ppz directed toward the viewer.
We
investigate this intercalative interaction of a metal bound ligand via various
spectroscopic methods, including uv-visible, fluorescence, circular dichroism
and resonance enhanced Raman spectroscopy; and by other physical chemical
techniques such as viscometry and equilibrium dialysis studies.
An especially
interesting aspect of the binding of these complexes to DNA is that it is
enantioselective. That is, one of a pair of enantiomers binds more strongly to
the DNA. For the ppz complex pictured above, the isomer displayed is the lambda
(L) which binds more
strongly to calf DNA than the ∆. In our studies, we have observed for the first
time enantioselective binding of a complex (1) which is likely not based on
intercalative binding, but on specific interaction of charges at the periphery
of the coordinated ligand, due to quaternized nitrogens, with the anionic
surface of the DNA.
Another
important aspect of the work involves the use of these complexes to carry other
metal ions, such as Cu(II) , to the DNA by coordinating to additional binding sites
at the periphery of the ligands (2). In the case of Cu(II) we have demonstrated
that cleavage of DNA can be accomplished in a system which also includes
ascorbate and oxygen by using such complexes. However, only the isomer which
binds within the minor groove of the DNA is effective in inducing cleavage.
This then is an enantioselective cleavage reagent for DNA.
Representative Publications:
"Inducement of Y-DNA Circular Dichroism Signals for Duplex Deoxyribonucleotide Homopolymers by Poly-cationic Strings," Thomas C. Strekas,* Robert Engel, Kishore Locknauth, JaimeLee Cohen and Jeanne Fabian, Archives of Biochem. Biophys. 364, 129-131. (1999)
R. Engel, V. Schevchenko, S. Lall, B. Tropp, N. Lau and T. Strekas, "Synthesis and Biological Activities of Phosphorous-Containing Polycationic Strings, " Phosphorous and Sulfur (in press). (1999)
J.I Cohen, A. Rusinowski, T.C. Strekas and R. Engel, "Polycations. 6. Polycationic Heterocyclic Salts: Their Synthesis and Effect on Double-Stranded DNA," Heteroatom Chemistry 10, 559-565. (1999)
Strekas, T.C.; Baker, A.D.; Zaltsman, L.; Wang, S. "Salt Dependence of binding of D- and L-Ru(2,2'-bipyridine)2ppz(+2) and a Chiragen Analog with Calf Thymus DNA: Unpredictability of Enantioselective Binding to DNA" J. Coord. Chem. 39, 281-291. (1997)
Strekas, T.C.; Baker, A.D. and Harripersad-Morgan, O. "Characterization of Copper(I) and Copper(II) Complexes of a Bis-diimine Coordinated to Ruthenium(II) and Their Interaction With Calf Thymus DNA." J. Coord. Chem. 34, 77-85. (1995)
Tysoe, S.A., Morgan, R.J., Baker, T.C. and Strekas, T.C. "Spectroscopic Investigation of Differential Binding Modes of Delta and Lambda-Ru(bpy)2ppz (2+) with Calf Thymus DNA." J. Phys. Chem. 97, 1707-1711. (1993)
Baker, A.D., Morgan, R.J. and Strekas, T.C. "Enantiospecific Cleavage of DNA Using Copper(II) Chelated to the Periphery of a Ligand on a Chiral Tris-Chelate of Ruthenium(II)" J. Chem. Soc. CHEM. COMM. 1992, 1099-1100.
Baker, A.D.; Morgan, R.J.; Strekas, T.C. "Enantiomeric Resolution of Ru(phen)3 (2+) and Ru(bpy)2ppz (2+) on a DNA-Hydroxyapatite Column," J. Amer. Chem. Soc. 113, 1411. (1991)
Morgan, R.J.; Chatterjee, S.; Baker, A.D.; Strekas, T.C. "Effects of Ligand Planarity and Peripheral Charge on Intercalative Binding of Ru(2,2'-bipyridine)2L (2+) to Calf Thymus DNA," Inorg. Chem. 30, 2687. (1991)