Ruthenium Tris(2-pyridylmethyl)amine as an Effective Photocaging Group for Nitriles

[Image: see text] 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)(2)](PF(6))(2) (1) and [Ru(TPA)(3)(2)](PF(6))(2) (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH(2)CN, and characterized by various spectroscopic techniques and mass spectrometry. Both 1 and 2 show the release of a single nitrile within 20 min of irradiation with 365 nm light. Complex 2 acts as a potent, photoactivated inhibitor of human cathepsin K. IC(50) values were determined for 2 and 3. Enzyme inhibition for 2 was enhanced by a factor of 89 upon exposure to light, with IC(50) values of 63 nM (light) and 5.6 μM (dark).