Molecule of the Week (06)
The molecule of the week originates from research at the Indian Institute of Science dealing with the photoactivation of oxovanadium complexes for photodynamic therapy (Sasmal, P.K.; Patra, A.K.; Nethaji, M. Chakravarty, A.R. Inorg. Chem. 2007, 46, 11112 – 11121). Photodynamic Therapy (PDT) is an anti-tumor therapy where the anti-tumor drug is activated by irradiation of the tumor with light. There are a couple of characteristics necessary for a potential PDT drug. The first is that it cannot exhibit any ‘dark’ activity; that is, it cannot be active without first being irradiated with light. The second is that the excitation wavelength should be as close to IR as possible. This allows for the light to penetrate the skin without damaging the healthy cells, which UV light would do. The oxovanadium complex in this research is the first vanadium complex to fulfill both of these requirements.
The mechanism of action is extremely interesting. The ligands on the vanadium first bind to the minor groove of the DNA. The complex is then irradiated with light, which activates the metal complex. The activation of the metal complex allows it to transform triplet oxygen, 3O2, into singlet oxygen, 1O2. Singlet oxygen is highly reactive and will react with any molecule in proximity, which in this case is DNA. The destruction of DNA by singlet oxygen leads to cell death even in tumor cells, allowing for the targeted destruction of tumors while leaving healthy cells intact. The only question I have is how molecules like this are metabolized in vivo. Would they stay bound to the DNA of healthy cells for an indefinite period of time and how would their presence affect the activity of cell machinery? Questions such as this need to be addressed, but the groundbreaking research done here is still vital to the search for anti-tumor drugs.