Synthesis of biologically important anti-cancer complexes with target ligands

1. Synthesis of Indenyl Ruthenium Complexes with Target Ligands
(Biologically Important Anti-cancer Complexes)
Akua Biaa Adu and Jocelyn Pineda Lanorio, Ph.D.
Illinois College Department of Chemistry, Jacksonville, IL 62650
Background
Conclusions
Objectives
Acknowledgements
Figure 2. The preparation and synthesis of the
indenyl ruthenium complexes were carried
out under inert and vacuum conditions.
• 2019 Illinois College Steven M. Tillery ‘72 Research Fund for Outstanding
Student
• Professor Clayton Spencer for an Introduction to Computational Chemistry.
• Andy Stice for lab assistance
• Illinois College Department of Chemistry
• Illinois College Experiential Learning Team
Results
Methodology
Figure 1. Structure of Indenyl (η5-C9H7) Ligand
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References
Scheme 1. Synthesis of
RuCl2(PPh3)3
Scheme 2. Synthesis of
IndRu(PPh3)2Cl
Scheme 4. Synthesis of
IndRu(PPh3)[P(OEt)3]Cl
Scheme 5. Chosen oxidation reaction for ruthenium catalysts.2
Figure 5. 1H NMR monitoring of the catalytic efficiency of
new IndRu(PPh3)2Cl complex (top) versus the traditional
RuCl2(PPh3)3 complex (bottom).
Ruthenium complexes have emerged as an attractive
alternative to platinum metal due to their low toxicity,
probable different mode of action, and diverse synthetic
chemistry.1 The interest in indenyl ligand originates from
its resemblance to ɳ5-cyclopentadienyl Cp/Cp* ligands.
• Air Sensitive Techniques
- Schlenk Line
• Refluxing
- Ligand addition
- Ligand substitution
• Product Extraction
- Filtration
- Rotavapor
• Nuclear Magnetic Resonance
- 1H, 13C, 31P
• A series of indenyl ruthenium complexes have been
successfully synthesized including the RAPTA anticancer
molecule IndRu(PPh3)(PTA)Cl, and 2 novel complexes
containing phosphite ligands.
• All prepared complexes are air-stable and have been
successfully characterized by NMR spectroscopy.
• IndRu(PPh3)2Cl is an efficient catalyst with higher % conversion
and TOF than the traditional RuCl2(PPh3)3.
• To synthesize air-stable indenyl ruthenium complexes with
phosphine and phosphite ligands.
• To fully characterize the series of prepared complexes
• Investigate if the synthesized ruthenium complexes can serve
as effective catalysts in a chosen oxidation reaction.
Scheme 3. Synthesis of
IndRu(PPh3)(PTA)Cl
Figure 4. 31P NMR Spectrum of
IndRu(PPh3)(PTA)Cl.
% Conversion TOF
2h RuCl2(PPh3)3 7-10% 5
2h IndRu(PPh3)2Cl 83.05% 48
• Indenyl effects
- η5, η3, η1 binding
• Anti-cancer
- platinum replacement
- more binding sites
- less toxic
Indenyl ruthenium complexes are known to exhibit reactivity
and stereochemical features different from those of the
corresponding Cp complexes, but evidence is still limited.
Figure 3. Appearance of
some of the
IndRu(PPh3)(PR3)Cl
complexes.
Future work
• Addition of a computational aspect to the research which may
include calculating the relative energy and stability of
synthesized compounds and analysis via computational
software such as Gaussian 16, MobaXterm, etc.
• Investigation of the catalytic efficiency of all the complexes
synthesized.
• Further application to other catalytic reactions and DNA-
binding activities.