1. Synthesis and biological activity studies of Schiff base ligand transition
metal complexes
Nathan Riggsbee, Amanda Koch, Amanda J. Crook. Department of Chemistry, Tennessee Technological University, Cookeville, TN 38505, United States
Abstract
Schiff bases are common ligands in coordination chemistry.
The transition metal complexes of these ligands, especially
those of platinum and palladium, have been shown in literature
to have antitumor activity. This research proposes the
synthesis and characterization of a class of Schiff base ligands
similar to the acetylacetonate (acac) ligands. These acac
transition metal complexes were synthesized using cobalt (II)
and copper (II). These metal complexes were then tested for
anti-proliferative activity against seven microbes, including
four bacteria strains, two yeast strains, and one mold strain.
The minimum inhibitory concentration (MIC) was determined
for the metal complexes. These complexes were expected to
show biological activity with different microorganisms.
Introduction
Schiff-Base metalloid ligands are compounds that have a
functional group that contains a carbon-nitrogen double bond,
where the nitrogen is also bonded to an aryl or alkyl group[1].
These compounds are used often in coordination chemistry
and biochemistry[1]. Ligands are microscopic molecules that
are found outside of the cellular membrane of an organism
that have the ability to enter the membrane of the cell through
various active and passive pathways, and have a reaction with
the intracellular receptors of the cell. The advantage of the
Schiff-Base ligands is that a compound can be created that
allows control over certain processes occurring within the
cell. This allows the potential use of these metalloid
compounds as a means to treat various cancers and tumors.
Oxindolime copper (II) and zinc (II) complexes are known to
inhibit the activity of certain DNA topoisomerase enzymes in
humans, and can be used for cancer treatment [2]. This project
focused on transition metal complexes that are synthesized by
using acetylacetonate (acac) ligands. The copper (II) acac
ligand synthesized can be used to catalyze coupling and
carbene transfer reactions [3] and the cobalt (II) acac ligand
can be used as an NMR shift reagent [4].
Acknowledgements
We would like to acknowledge Ed Lisic for use of space and supplies, and for help in starting
this project.
References
[1] IUPAC, Compendium of Chemical Terminology, 2nd
Ed. (1997)
[2] R. Pankajavilli, et.al. Thermal stability of organo-chromium or chromium organic complexes
and vapor pressure measurements on tris(2,4-pentanedionato)chromium(III) and hexacarbonyl
chromium(0) by TG-based transpiration method. Chemical Engineering Science 57 (2002) 3603-
3610.
[3] E. J. Parish, S. Li "Copper(I) Acetylacetonate" in Encyclopedia of Reagents for Organic
Synthesis. (2004)
[4] H.M. Goff, et. al. “Synthesis, Charactersization, and Use of a Cobalt(II) Complex as an NMR
Shift Reagent”. J Chem Ed. 59 (5), (1982)
[5] “Synthesis of Metal Acetylacetonate Complexes. zyxel-
nsa210.lilu2.ch/MyWeb/public/.../sintesi_acetiacetonati.doc. Accessed September 2013.
Discussion
The synthesis of the Cu(acac)2 and the Co(acac)2
complexes were both successful and gave reasonable
percent yields. Both products were successfully
recrystallized. The bacterial studies showed that both
compounds had little to no effect on all of the cultures
of bacteria and fungi. Finally, the UV-Vis spectra
revealed that the Cu(acac)2 ligand and the Co(acac)2
complexes had a λmax of 632 nm and 491 nm,
respectively.
Experimental
Synthesis of the Co(acac)2 and Cu(acac)2 complexes were conducted and the products
were recrystallized via published literature methods [4,5].
Bacterial studies were conducted by placing the bacteria listed in Tables 1 and 2 in a
Thioglycollate broth which was then inoculated with a solution containing the
Co(acac)2 and Cu(acac)2. The concentration used decreased in each trial by a factor of
two. The resulting mixture was incubated, and was then tested for bacteria that
survived the metal complex inoculation.
UV-Vis spectral data was collected by preparing solutions that gave an absorbance
reading in the range of 0.1-1 absorbance units. The wavelength of maximum
absorbance was determined in the wavelength range of 400-800 nm..
[Co(Acac)2(OH)2] 100 mg
Conc 1 2 3 4 5 6 7 8 9 10 Bact control
ug/mL 250.0 125.0 62.5 31.25 15.625 7.8125 3.906 1.953 0.9766 0.4883
Microrg
Sacchromyces cerevisiae + + + + + + + + + + +
Aspergillus niger + + + + + + + + + + +
Candida albicans + + + + + + + + + + +
Pseudomonas aeruginosa + + + + + + + + + + +
Escherichia coli + + + + + + + + + + +
Bacillus subtilis + + + + + + + + + + +
Staphylococcus aureus + + + + + + + + + + +
[Cu(Acac)2] 50mg
Conc 1 2 3 4 5 6 7 8 9 10 Bact control
ug/mL 125.0 62.5 31.3 15.63 7.8125 3.9063 1.953 0.977 0.4883 0.2441
Microrg
Sacchromyces cerevisiae + + + + + + + + + + +
Aspergillus niger + + + + + + + + + + +
Candida albicans + + + + + + + + + + +
Pseudomonas aeruginosa + + + + + + + + + + +
Escherichia coli + + + + + + + + + + +
Bacillus subtilis + + + + + + + + + + +
Staphylococcus aureus + + + + + + + + + + +
Table 2: MIC data for Cu(acac)2
Figure 2: Determination of λmax of Cu(acac)2
Figure 1: General synthesis of acetylacetonate metal complexes
Results
(a) (b)
(c) (d)
Figure 4: (a) Cu(acac)2 precipitate, (b): Co(acac)2
precipitate, (c): Cu(acac)2-methanol solution, (d):
Co(acac)2 synthesis
Figure 3: Determination of λmax of Co(acac)2
Table 1: MIC data for Co(acac)2