1. Synthesis, Spectral Characterization, and Nucleic Acids Interactions of Nickel (II)-Salen complex
Olivia F. Hurst, Dana Warwick, Dr. Roslyn Theisen , and Dr. Sanchita Hati ❖
Department of Chemistry ❖University of Wisconsin-Eau Claire ❖Eau Claire, WI 54701❖Spring 2015
18 bold for graphs
[2] Burrows, C.J., Rokita, S.E. Acc. Chem. Res. 1994, 27,
[3] Journal of Bimolecular Screening. 2011, 16,
[4] S. Routier, H. Vezin, E. Lamour, J.-L. Bernier, J.-P. Catteau, and C. Bailly. DNA cleavage by hydroxy-salicylidene-ethylendiamine-iron complexes. Nucleic Acids Research. 1999, 27:
Abstract
Around the world, cancer is one of the leading causes of death. DNA is the primary target molecule for most anticancer therapy. Transition metal complexes are known to have DNA binding and cleavage properties under physiological conditions. Currently, we are investigating the interactions between a number of nickel (II) complexes and nucleic acids (DNA/RNA) in an attempt to design and develop metal complexes that can have more efficiency in nucleic acids binding and cleavage and therefore, could be used in cancer chemotherapy. We have synthesized Nickel (II)-Salen complex and the synthesized product was characterized by UV-Vis spectroscopy and FT-IR. We are currently studying the interactions between the Nickel (II)-Salen complex and nucleic acids using UV-Vis spectroscopy and gel electrophoresis. We will present the preliminary results of our study. Our overall goal is to synthesize transition metal complexes that could bind or cleave the target DNA/RNA molecules and effective in the cancer treatment. This study could have major implications on the drug and health industry and potentially be a cure for cancer. ​
Introduction
Complex Synthesis
Interaction between [Ni(II)(salen)] and DNA/RNA
Transition metal complexes are widely used in the medicine industry as an anti-cancer drug. In 1964, a cis-Platinum [Pt(NH3)2Cl2] was first reported to have the ability to suppress cell division. This showed promise for transition metal-based drugs to cure cancer cell growth. Many metal complexes show affinity for binding to the target DNA. The metal-DNA interaction can occur in two ways: diffuse and site binding. Diffuse binding is a long range interaction in which the metal ions interact with the nucleic acid through water interactions [1]. In site binding, the nucleic acids bind/interact directly to the ligands surrounding the metal ion or with the metal ion itself [1].
Many transition metal complexes have also attracted a lot of attention due to their DNA binding and cleavage properties. For example, salen-Ni (II) complexes can be used for the cleavage of guanine structures in DNA and RNA[2]. The salen complexes have flexible conformations and can have a variety of geometries [3]. Also, the flat, electron-rich aromatic surfaces of salen metal complexes may assist in their interactions with nucleic acids [3]. Hydroxyl groups in the salen complexes cooperate to form free radicals responsible for DNA cleavage [4].
The [N,N’-Ethylene-bis(salicylideneiminato)]-nickel(II), [Ni(II)(salen)] complex was synthesized via a previously reported method, which involves a two-step reaction:
The interatcions betweem [Ni(II)(salen)] complex and tRNA were studied by UV-Vis spectroscopy.
Synthesis of [Sal2Ni(H2O)2]
Synthesis of [Ni(II)(salen)] Ni
Figure 3. UV-Vis Spectrum of 1.0 mM [Ni(II)(salen)] complex with varying concentrations of DNA. The buffer used was Tris (5 mM, pH 8.0) and NaCl (O.5 mM), 30 uL; acetonitrile, 80 uL; and differing amounts of H2O.
Characterization of [Ni(II)(salen)] complex
The Spectroscopic properties of the [Ni(II)(salen)] complex bound with DNA were studied by UV-Vis.
% Transmittance
*C=N =
cm-1
Figure 4. UV-Vis Spectrum of 0.1 mM [Ni(II)(salen)] complex with varying concentrations of tRNA. The buffer used was Tris (5 mM, pH 8.0) and NaCl (O.5 mM), 30 uL; acetonitrile, 80 uL; and differing amounts of H2O.
Figure 1. Infrared graph of the [Ni(salen)] complex.
Wavenumber (cm-1)
This peak at cm-1represents the C=N imine bond and confirmed that the synthesized complex is indeed [Ni(II)(salen)] complex.
Conclusions
We were successful in synthesizing the [Ni(II)(salen)] complex. This is evident from the presence of imine (C=N) band at cm-1 in the IR spectra and a presence of absorption maxima at 330 and 420 nm in the UV-Vis spectra.
The binding of [Ni(II)(salen)] complex to the target DNA (puc 19) was evident from the change in the absorption spectra in the presence of variable concentrations of DNA molecule.
The interatcion between [Ni(II)(salen)] complex and tRNA is revealed from the decrease in absortion at 330 and 420 nm.
 = 330 nm
Absorbance
 = 420 nm
Objectives
The objective of this project is to synthesize transition metal-based complexes that will be more efficient in binding or cleaving target DNA/RNA and therefore, could be used in cancer treatment.
In our current studies, we aim to synthesize Ni (II) and other transition metal complexes and characterize them through IR and UV-spectroscopy. After these complexes are being successfully synthesized and characterized, we will study their interactions with DNA/tRNA using UV-Vis spectroscopy. We will monitor the extent of cleavage of DNA/tRNA through gel electrophoresis.
Wavenumber (nm)
Future Work
Figure 2. UV-Vis Spectrum of 0.1 mM [Ni(II)(salen)] complex.
Current work is focused on the binding of the [Ni(II)(salen)] complex with tRNA and DNA. In the future, we will continue testing the [Ni(II)(salen)] complex binding capabilities to nucleci acids through gel electrophoresis. We will also synthesize other metal complexes and will test their ability to bind or cleave the target tRNA and DNA molecules through UV-Vis spectroscopy and gel electrophoresis.
References
[1] Johnson, Arish; Sivasankaran, Nair. Synthesis, characterization and biological studies on some metal complexes with Schiff base ligand containing pyrazolone moiety. Journal of Saudi Chemical Society. 2013, 1-8.
[2] Burrows, C.J., Rokita, S.E. Acc. Chem. Res. 1994, 27,
[3] Journal of Bimolecular Screening. 2011, 16,
[4] S. Routier, H. Vezin, E. Lamour, J.-L. Bernier, J.-P. Catteau, and C. Bailly. DNA cleavage by hydroxy-salicylidene-ethylendiamine-iron complexes. Nucleic Acids Research. 1999, 27: