Hypoxic tumours are a major problem for cancer photodynamic therapy. Here, we show that photoredox catalysis can provide an oxygen-independent mechanism of action to combat this problem. We have designed a highly oxidative Ir(III) photocatalyst, [Ir(ttpy)(pq)CI]PF6 ([1]PF6, where 'ttpy' represents 4'-(p-tolyl)-2,2':6',2 "-terpyridine and 'pq' represents 3-phenylisoquinoline), which is phototoxic towards both normoxic and hypoxic cancer cells. Complex 1 photocatalytically oxidizes 1,4-dihydronicotinamide adenine dinucleotide (NADH)-an important coenzyme in living cells-generating NAD center dot radicals with a high turnover frequency in biological media. Moreover, complex 1 and NADH synergistically photoreduce cytochrome c under hypoxia. Density functional theory calculations reveal pi stacking in adducts of complex 1 and NADH, facilitating photoinduced single-electron transfer. In cancer cells, complex 1 localizes in mitochondria and disrupts electron transport via NADH photocatalysis. On light irradiation, complex 1 induces NADH depletion, intracellular redox imbalance and immunogenic apoptotic cancer cell death. This photocatalytic redox imbalance strategy offers a new approach for efficient cancer phototherapy.

We explore the ultrafast photoprotective properties of a series of sinapic acid derivatives in a range of solvents, utilizing femtosecond transient electronic absorption spectroscopy. We find that a primary relaxation mechanism displayed by the plant sunscreen sinapoyl malate and other related molecular species may be understood as a multistep process involving internal conversion of the initially photoexcited 1(1)ππ* state along a trans-cis photoisomerization coordinate, leading to the repopulation of the original trans ground-state isomer or the formation of a stable cis isomer.

The excited-state dynamics of phenol following ultraviolet (UV) irradiation have received considerable interest in recent years, most notably because they can provide a model for understanding the UV-induced dynamics of the aromatic amino acid tyrosine. Despite this, there has been some debate as to whether hydrogen tunneling dynamics play a significant role in phenol's excited-state O-H bond fission when UV excitation occurs below the (1)ππ*/(1)πσ* conical intersection (CI). In this Letter, we present direct evidence that (1)πσ*-mediated O-H bond fission below the (1)ππ*/(1)πσ* CI proceeds exclusively through hydrogen tunneling dynamics. The observation of hydrogen tunneling may have some parallels with proton tunneling dynamics from tyrosine residues (along the O-H bond of the phenol moiety) in a wide range of natural enzymes, potentially adding further justification for utilizing phenols as model systems for investigating tyrosine-based dynamics.

A combination of ultrafast time-resolved velocity map imaging (TR-VMI) methods and complete active space self-consistent field (CASSCF) ab initio calculations are implemented to investigate the electronic excited-state dynamics in aniline (aminobenzene), with a perspective for modeling (1)πσ* mediated dynamics along the amino moiety in the purine derived DNA bases. This synergy between experiment and theory has enabled a comprehensive picture of the photochemical pathways/conical intersections (CIs), which govern the dynamics in aniline, to be established over a wide range of excitation wavelengths. TR-VMI studies following excitation to the lowest-lying (1)ππ* state (1(1)ππ*) with a broadband femtosecond laser pulse, centered at wavelengths longer than 250 nm (4.97 eV), do not generate any measurable signature for (1)πσ* driven N-H bond fission on the amino group. Between wavelengths of 250 and >240 nm (<5.17 eV), coupling from 1(1)ππ* onto the (1)πσ* state at a 1(1)ππ*/(1)πσ* CI facilitates ultrafast nonadiabatic N-H bond fission through a (1)πσ*/S(0) CI in <1 ps, a notion supported by CASSCF results. For excitation to the higher lying 2(1)ππ* state, calculations reveal a near barrierless pathway for CI coupling between the 2(1)ππ* and 1(1)ππ* states, enabling the excited-state population to evolve through a rapid sequential 2(1)ππ* → 1(1)ππ* → (1)πσ* → N-H fission mechanism, which we observe to take place in 155 ± 30 fs at 240 nm. We also postulate that an analogous cascade of CI couplings facilitates N-H bond scission along the (1)πσ* state in 170 ± 20 fs, following 200 nm (6.21 eV) excitation to the 3(1)ππ* surface. Particularly illuminating is the fact that a number of the CASSCF calculated CI geometries in aniline bear an exceptional resemblance with previously calculated CIs and potential energy profiles along the amino moiety in guanine, strongly suggesting that the results here may act as an excellent grounding for better understanding (1)πσ* driven dynamics in this ubiquitous genetic building block.