Cytochrome P450 Induction through the Efficient Photoinduced Release of a Pyridine-Substituted Agent from Ru(II)

We report the first example of using photoinduced ligand release from a Ru(II) complex for light-triggered cytochrome P450 (CYP) induction. CYPs are pivotal enzymes in biosynthesis and drug metabolism, and their induction can be leveraged for therapeutics and biochemical research. We show the activation of a CYP1A1 with visible light through the efficient photorelease of an aryl hydrocarbon receptor (AHR; <b>1</b>) agonist with a quantum yield, Φ₅₀₀, of 0.16(1) with λ_irr = 500 nm in [Ru(tpy)(Me₂bpy)(<b>1</b>)]²⁺ (tpy = 2,2':6',2″-terpyridine, Me₂bpy = 6,6'-dimethyl-2,2'-bipyridine). This value is consistent with that previously reported for pyridine (py) exchange in the analogous [Ru(tpy)(Me₂bpy)(py)]²⁺ complex, Φ₅₀₀ = 0.16(1), which is driven by steric effects. In contrast to [Ru(tpy)(bpy)(py)]²⁺ (bpy = 2,2'-bipyridine), with Φ₅₀₀ < 10^-4, the ligand photodissociation in [Ru(tpy)(bpy)(<b>1</b>)]²⁺ proceeds with Φ₅₀₀ = 0.015(1), at least 2 orders of magnitude more efficiently. Similarly, [Ru(tpy)(biq)(<b>1</b>)]²⁺ (<b>4</b>; biq = 2,2'-biquinoline) undergoes photoinduced exchange of <b>1</b> with CH₃CN solvent with Φ₅₀₀ = 0.064(3), more efficiently than [Ru(tpy)(biq)(py)]²⁺ with Φ₅₀₀ = 0.03. Through experiments and calculations, we show the involvement of intraligand charge transfer (ILCT) within the leaving ligand in an unprecedented mechanism for ligand photodissociation from Ru(II). Chemical tools based on these findings hold the promise of advancing research on tissue-specific CYP activity by enabling precise spatiotemporal control. Moreover, these compounds may pave the way for the development of highly specific and light-activated pharmaceuticals that enhance the synergy with existing drugs.