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.

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.

The challenges of using modern theoretical and computational tools to model the unique features of the oxygen-organic molecule photosystem are discussed from a historical and pedagogical perspective. This review is written for the novice, but the problems formulated should stimulate the expert.

Time-resolved photoelectron imaging was used to investigate the dynamical evolution of the initially prepared S(1) (ππ*) excited state of phenol (hydroxybenzene), catechol (1,2-dihydroxybenzene), resorcinol (1,3-dihydroxybenzene), and hydroquinone (1,4-dihydroxybenzene) following excitation at 267 nm. Our analysis was supported by ab initio calculations at the coupled-cluster and CASSCF levels of theory. In all cases, we observe rapid (<1 ps) intramolecular vibrational redistribution on the S(1) potential surface. In catechol, the overall S(1) state lifetime was observed to be 12.1 ps, which is 1-2 orders of magnitude shorter than in the other three molecules studied. This may be attributed to differences in the H atom tunnelling rate under the barrier formed by a conical intersection between the S(1) state and the close lying S(2) (πσ*) state, which is dissociative along the O-H stretching coordinate. Further evidence of this S(1)/S(2) interaction is also seen in the time-dependent anisotropy of the photoelectron angular distributions we have observed. Our data analysis was assisted by a matrix inversion method for processing photoelectron images that is significantly faster than most other previously reported approaches and is extremely quick and easy to implement.

Porphycenes are structural isomers of porphyrins that have many unique properties and features. In the present work, the resonant two-photon absorption of 2,7,12,17-tetraphenylporphycene (TPPo) and its palladium(II) complex (PdTPPo) has been investigated. The data obtained are compared to those from the isomeric compound, meso-tetraphenylporphyrin (TPP). Detection of phosphorescence from singlet molecular oxygen, O2(a(1)Delta(g)), produced upon irradiation of these compounds, was used to obtain two-photon excitation spectra and to quantify two-photon absorption cross sections, delta. In the spectral region of 750-850 nm, the two-photon absorption cross sections at the band maxima for both TPPo and PdTPPo, delta = 2280 and 1750 GM, respectively, are significantly larger than that for TPP. This difference is attributed to the phenomenon of so-called resonance enhancement; for the porphycenes, the two-photon transition is nearly resonant with a comparatively intense one-photon Q-band transition. The results of quantum mechanical calculations using density functional quadratic response theory are in excellent agreement with the experimental data and, as such, demonstrate that comparatively high-level quantum chemical methods can be used to interpret and predict nonlinear optical properties from such large molecular systems. One important point realized through these experiments and calculations is that one must exercise caution when using qualitative molecular-symmetry-derived arguments to predict the expected spectral relationship between allowed one- and two-photon transitions. From a practical perspective, this study establishes that, in comparison to porphyrins and other tetrapyrrolic macrocyclic systems, porphycenes exhibit many desirable attributes for use as sensitizers in two-photon initiated photodynamic therapy.

We present a detailed study of the effects of electron correlation on two-photon absorption calculated by coupled cluster quadratic response theory. The hierarchy of coupled cluster models CCS, CC2, CCSD, and CC3 has been used to investigate the effects of electron correlation on the two-photon absorption cross sections of formaldehyde (CH2O), diacetylene (C4H2), and water (H2O). In particular, the effects of triple excitations on two-photon transition cross sections are determined for the first time. In addition, we present a detailed comparison of the coupled cluster results with those obtained from Hartree-Fock and density-functional response theories. We have investigated the local-density approximation, the pure Becke-Lee-Yang-Parr (BLYP) functional, the hybrid Becke-3-parameter-Lee-Yang-Parr (B3LYP), and the Coulomb-attenuated B3LYP (CAM-B3LYP) functionals. Our results show that the CAM-B3LYP functional, when used in conjuction with a one-particle basis-set containing diffuse functions, has much promise; however, care must still be exercised for diffuse Rydberg-type states.

Time-resolved photoelectron spectroscopy was used to obtain new information about the dynamics of electronic relaxation in gas-phase indole and 5-hydroxyindole following UV excitation with femtosecond laser pulses centred at 249 nm and 273 nm. Our analysis of the data was supported by ab initio calculations at the coupled cluster and complete-active-space self-consistent-field levels. The optically bright 1 L a and 1 L b electronic states of 1 ππ* character and spectroscopically dark and dissociative 1 πσ* states were all found to play a role in the overall relaxation process. In both molecules we conclude that the initially excited 1 L a state decays non-adiabatically on a sub 100 fs timescale via two competing pathways, populating either the subsequently long-lived 1 L b state or the 1 πσ* state localised along the N-H coordinate, which exhibits a lifetime on the order of 1 ps. In the case of 5-hydroxyindole, we conclude that the 1 πσ* state localised along the O-H coordinate plays little or no role in the relaxation dynamics at the two excitation wavelengths studied.

Ultrafast time-resolved velocity map ion imaging (TR-VMI) and time-resolved ion-yield (TR-IY) methods are utilised to reveal a comprehensive picture of the electronic state relaxation dynamics in photoexcited catechol (1,2-dihydroxybenzene). After excitation to the S1 ((1)ππ*) state between 280.5 (the S1 origin band, S1(v = 0)) to 243 nm, the population in this state is observed to decay through coupling onto the S2 ((1)πσ*) state, which is dissociative with respect to the non-hydrogen bonded 'free' O-H bond (labelled O(1)-H). This process occurs via tunnelling under an S1/S2 conical intersection (CI) on a timeframe of 5-11 ps, resulting in O(1)-H bond fission along S2. Concomitant formation of ground state catechoxyl radicals (C6H5O2(X)), in coincidence with translationally excited H-atoms, occurs over the same timescale as the S1 state population decays. Between 254-237 nm, direct excitation to the S2 state is also observed, manifesting in the ultrafast (~100 fs) formation of H-atoms with high kinetic energy release. From these measurements we determine that the S1/S2 CI lies ~3700-5500 cm(-1) above the S1(v = 0) level, indicating that the barrier height to tunnelling from S1(v = 0) → S2 is comparable to that observed in the related 'benchmark' species phenol (hydroxybenzene). We discuss how a highly 'vibrationally-enhanced' tunnelling mechanism is responsible for the two orders of magnitude enhancement to the tunnelling rate in catechol, relative to that previously determined in phenol (>1.2 ns), despite similar barrier heights. This phenomenon is a direct consequence of the non-planar S1 excited state minimum structure (C1 symmetry) in catechol, which in turn yields relaxed symmetry constraints for vibronic coupling from S1(v = 0) → S2- a scenario which does not exist for phenol. These findings offer an elegant example of how even simple chemical modifications (ortho-hydroxy substitution) to a fundamental, biologically relevant, UV chromophore, such as phenol, can have profound effects on the ensuing excited state dynamics.