Figure 1. The allylcarbamate deprotection. The chemical product (green), the Pd microspheres (red) are present in the nucleus (blue). Taken from Ref. [1].
This piece of impressive work involves a grand Ménage à trois of chemistry, biology and materials. The workers carry out Pd(0)-catalyzed reactions in a cell, using an heterogeneous Pd(0) catalyst.
They use palladium nanoparticles, which are trapped with polystyrene microsphere. This approach can prevent the potential toxicity of palladium towards cells. They load the HeLa cells with fluorescently labeled Pd(0) microspheres. Then, they add in the relevant chemical substrates to test if Pd(0)-catalyzed reaction take place. The 2 reactions they elect to study are: an allylcarbamate deprotection and the Suzuki reaction.
First, for the allylcarbamate deprotection (Figure 2). The chemical substrates are lipophilic, which means they are capable of crossing the cell-membrane to the intracellular regions. They are also non-fluorescent. The curious aspect is that if the reactions do occur, they will be ‘unlocked’ and become fluorescent. As the fluorescent chemical products are retained within the cell, we will be able to observe these compounds using both Fluorescene and confocal microscopy.
For example, the allylcarbamate cleavage will lead to the liberation of the amino group in compound 2 – and the electron density of the amino group will set up the π-electron conjugation in the product structure. (Figure 2) We will observe the fluorescent emission at 521 nm. Indeed, a confocal microscopy image shows the presence of both the product 2 and the Pd(0) microsphere in the cell. (Figure 1)
Figure 2. The concept of the allylcarbamate deprotection. Taken from Ref. [1].
For the Suzuki scenario, it is a bit more intriguing. (Figure 3) The two coupling partners are both lipophilic and non-fluorescent. When they are both internalized into the HeLa cells, loaded with Pd(0) microsphere, the cross-coupling reaction occurs. Upon the hydrolysis of the lactone moiety, the resultant carboxylate once again sets up the π-electron conjugation of the product, and fluorescene emission occurs. Another interesting aspect, for which cell biologists may be interested, is that the chemical product will localize to mitochondria, due to the presence of the lipophilic cationic triphenylphosphonium group on the structure of the product [2].
Figure 3. The concept of the Suzuki reaction. Taken from Ref. [1].
The confocal microscopy image nicely illustrates this observation. (Figure 4) For the controls, the red colour signifies the mitochondria and the blue signifies the cell nucleus. Upon the Suzuki reaction, the chemical compound is shown in green and it clearly localizes to the mitochondira.
Figure 4. The confocal images for the Suzuki reaction. The diagram on the left is the control, for which the nucleus is shown in blue and the mitochondria is red. For the diagram on the right, the Suzuki reaction has taken place and it is clear that the fluorescent chemical product (green) is localized in the mitochondria of the cell. Taken from Ref. [1].
This work means that further developments will lead to great applications in chemical biology and drug delivery. More importantly, this is a multidisciplinary research project, and is of interest to chemists enthusiastic about catalysis, cell biologists and materials scientists. A truly spectacular piece of work!
-Ed Law 11/02/2011
This work is covered in RSC Chemistry World Website. [3]
http://www.rsc.org/chemistryworld/News/2011/February/06021101.asp
References:
1. Palladium-mediated intracellular chemistry
Rahimi M. Yusop, Asier Unciti-Broceta, Emma M. V. Johansson, Rosario M. Sánchez-Martín & Mark Bradley
Nature Chemistry, 6 February 2011.
doi:10.1038/nchem.981
2. Delivery of bioactive molecules to mitochondria in vivo.
Smith, R. A., Porteous, C. M., Gane, A. M. & Murphy, M. P.
Proc. Natl Acad. Sci. USA 2003, 100, 5407–5412.
3. http://www.rsc.org/chemistryworld/News/2011/February/06021101.asp
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