1. What is the chemical problem? Why is the problem important?
The chemical problem explored in this research is based upon anticancer agents and enzyme inhibitors. The scientists looked for caging groups other than the known Ru(bpy)2 that would bond biologically active molecules to either organic or metal-based protecting groups cleaved with light. These species would be used in medical situations to treat neurotransmitter defects, cancers, and enzyme dysfunctions.

2. What information is needed to solve the problem?
One piece of extremely important information is that in the past, the potential caging groups tested have been similar to bpy in their structure; they have been planar, chelating ligands. The most widely used inorganic protecting group is (Ru)bpy2. This group can cage neurotransmitters and is used in a multitude of medical applications.

3. What was the experimental method? Were there any particular criteria that were considered in designing this experiment? How was the experimental method validated?
Two complexes, [Ru(TPA)(RCN)2](PF6)2 and [Ru(TPA)(RCN)2](PF6)2 were prepared. After preparation, the compounds were put through a multitude of tests. These included UV-vis, NMR, IR spectroscopy, in addition to electrospray ionization mass spectrometry. The first complex was also tested with X-ray crystallography. They were tested for release of nitrile ligands by being decomposed in DMSO and phosphate-buffered saline. The complexes were also tested for enzyme inhibition.

4. What were the results?
The scholars found that complex 2 is a light-activated inhibitor of human cathepsin K, and that enzyme inhibition for the complex was enhanced with exposure to light. With complex 1, the control showed that there was no inhibition of cathepsin K under neither light nor dark conditions. This assumes that the ruthenium complex nor the byproduct causes the inhibition in the second complex.

5. What do the results mean? How do they fit into the context of the chemical problem?
With the caged inhibitor complex 2, efficient photoactivated enzyme inhibition against human cathepsin K was demonstrated. This is important because it is unlike Ru(bpy)2, and this could lead to new applications in the biological world. Since the Ru(bpy)2 has been used to cage neurotransmitters, fight cancer, and inhibit enzymes, the new caging group could be used to do the same, and more, in the field of medicine.

6. Was there a successful conclusion to the problem?
There was a successful conclusion to the problem, and that is that the second complex is able to inhibit human cathepsin K. While this is a good starting point, more research is needed in order to fully understand the potential biological effects this may have on our population. The authors of this article are currently working on further research with this caging group, using steady-state and time-resolved techniques to understand the photochemistry of the nitrile release. They are also figuring out how to lower the energy of light needed for ligand exchange, and exploring uses of the caging group in biological situations.

7. Identify at least one reference from each section of the journal article that would provide necessary background information or enrich your understanding of the presented material. Provide the citations for these references and explain why you chose them.

The first reference I chose explains the link between the Ru(bpy)2 photocaging protecting group and its uses in anticancer agents. This is important because it enriches my understanding of the biomedical applications of these caging groups, and the potential that new caging groups may fulfill.
Garner, R. N.; Gallucci, J. C.; Dunbar, K. R.; Rurro, C. Inorg. Chem. 2011, 50, 9213-9215.

The second reference I chose compares nitrile binding between ruthenium(II) and the newly synthesized complexes using IR spectra. This is important because the entire focus of this study was to determine if there were other differently structured, yet similarly bonding groups like ruthenium. This reference includes some of the information needed to compare these caging groups.
Cruz, A. J.; Kirgan, R.; Siam, K.; Heiland, P.; Rillema, D. P. Inorg. Chim. Acta 2010, 363, 2496-2505.

The last reference I chose explains the metal-to-ligand charge transfer bands observed with irradiation in both complexes. This is important because it can help explain some of the results of the experiment in terms of how the complexes release the nitrile ligands.
Kojima, T.; Amano, T.; Ishii, Y.; Ohba, M.; Okaue, Y.; Matsuda, Y. Inorg. Chem. 1998, 37, 4076-4085.