Ruthenium tris(2-pyridylmethyl)amine as an effective photocaging group for nitriles

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)2](PF 6)2 (1) and [Ru(TPA)(3)2](PF6) 2 (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH 2CN, 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). © 2014 American Chemical Society.