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

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]­(PF6)2 (1) and [Ru­(TPA)­(3)2]­(PF6)2 (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH2CN, 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. IC50 values were determined
for 2 and 3. Enzyme inhibition for 2 was enhanced by a factor of 89 upon exposure to light, with
IC50 values of 63 nM (light) and 5.6 μM (dark).