Ruthenium
Tris(2-pyridylmethyl)amine as an Effective
Photocaging Group for Nitriles
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Abstract
Ruthenium(II)
tris(2-pyridylmethyl)amine (TPA) is an effective caging group for
nitriles that provides high levels of control over the enzyme activity
with light. Two caged nitriles were prepared, [Ru(TPA)(MeCN)<sub>2</sub>](PF<sub>6</sub>)<sub>2</sub> (<b>1</b>) and [Ru(TPA)(<b>3</b>)<sub>2</sub>](PF<sub>6</sub>)<sub>2</sub> (<b>2</b>), where <b>3</b> is the cathepsin K inhibitor Cbz-Leu-NHCH<sub>2</sub>CN, and characterized by various spectroscopic techniques
and mass spectrometry. Both <b>1</b> and <b>2</b> show
the release of a single nitrile within 20 min of irradiation with
365 nm light. Complex <b>2</b> acts as a potent, photoactivated
inhibitor of human cathepsin K. IC<sub>50</sub> values were determined
for <b>2</b> and <b>3</b>. Enzyme inhibition for <b>2</b> was enhanced by a factor of 89 upon exposure to light, with
IC<sub>50</sub> values of 63 nM (light) and 5.6 μM (dark)
