Mechanisms of singlet-oxygen and superoxide-ion generation by porphyrins and bacteriochlorins and their implications in photodynamic therapy.

New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.

Exothermic rate restrictions in long-range photoinduced charge separations in rigid media.

Glycerol/methanol (9:1) mixtures at 255 K behave as rigid media for photoinduced electron transfers that take place within a few hundred nanoseconds. This media also provides enough polarity and plasticity to accommodate charge separations with reaction free energies ranging from +3 to -34 kcal/mol. The distance dependence of the electron transfer rates from electronically excited aromatic hydrocarbons to nitriles in this medium is accurately described by an exponential decay constant of 1.65 per angstrom. These photoinduced electron transfers display, for the first time in charge separations between independent electron donors and acceptors, a free-energy relationship with a maximum rate followed by a decrease in the rate for more exothermic reactions. According to this free-energy relationship, Franck-Condon factors are maximized at DeltaG(0) approximately -15 kcal/mol. It is suggested that the inverted region observed for these first-order photoinduced charge separations originates from a slower increase of their reorganization energies with DeltaG(0) than that of the analogous second-order photoinduced charge separations, for which inverted regions have never been clearly observed.

Understanding chemical reactivity: the case for atom, proton and methyl transfers.

The concept of "chemical reactivity" assumes that atoms and molecules contain the necessary information to describe their evolution over time as they transform from reactants to products. This concept was useful in the past to rationalize reactivity trends and predict the behavior of new systems. Free-energy relationships have played a central role in this field. However, electronic effects often counter the energetic effects and give rise to "anomalies" or separate correlations. We discuss a quantification of the concept of "chemical reactivity", emphasizing the role of molecular and electronic factors in chemistry.

The rates of S(N)2 reactions and their relation to molecular and solvent properties.

The energy barriers of symmetrical methyl exchanges in the gas phase have been calculated with the reaction path of the intersecting/interacting-state model (ISM). Reactive bond lengths increase down a column of the Periodic Table and compensate for the decrease in the force constants, which explains the near constancy of the intrinsic barriers in the following series of nucleophiles: F(-) approximately Cl(-) approximately Br(-) approximately I(-). This compensation is absent along the rows of the Periodic Table and the trend in the reactivity is dominated by the increase in the electrophilicity index of the nucleophile in the series C

Absolute rate calculations. Proton transfers in solution.

The reaction path of the intersecting-state model is used in transition-state theory with the semiclassical correction for tunneling (ISM/scTST) to calculate the rates of proton-transfer reactions from hydrogen-bond energies, reaction energies, electrophilicity indices, bond lengths, and vibration frequencies of the reactive bonds. ISM/scTST calculations do not involve adjustable parameters. The calculated proton-transfer rates are within 1 order of magnitude of the experimental ones at room temperature, and cover very diverse systems, such as deprotonations of nitroalkanes, ketones, HCN, carboxylic acids, and excited naphthols. The calculated temperature dependencies and kinetic isotope effects are also in good agreement with the experimental data. These calculations elucidate the roles of the reaction energy, electrophilicity, structural parameters, hydrogen bonds, tunneling, and solvent in the reactivity of acids and bases. The efficiency of the method makes it possible to run absolute rate calculations through the Internet.

Dramatic pressure-dependent quenching effects in supercritical CO2 assessed by the fluorescence of 4'-dimethylamino-3-hydroxyflavone. Thermodynamic versus kinetics control of excited-state intramolecular proton transfer.

Steady-state fluorescence of 4'-dimethylamino-3-hydroxyflavone (DMA3HF) was observed in supercritical carbon dioxide (scCO(2)). Excited-state intramolecular proton transfer (ESIPT) occurs resulting in two well-separated emission bands corresponding to the normal and tautomer forms. As the scCO(2) density exceeds 0.7 g/mL, the relative intensity of the two bands tends to a constant value, comparable to that observed for organic solvents with ET(30) = 33.0 +/- 0.5 kcal/mol, such as toluene and di-n-butyl ether. At lower densities, the substantial decrease of the total fluorescence intensity (a 600-fold decrease as the pressure decreases from 100 to 80 bar) is accompanied by an even more accentuated decrease of the tautomer fluorescence. This can be explained by a shift in the equilibrium between normal and tautomer forms, concomitant with a more efficient quenching of the less solvated fluorophore, that may change the thermodynamic control of the relative population of the two emissive species to a kinetic control.

Temperature dependence of ultra-exothermic charge recombinations.

We measured the temperature dependence (from +32 to -50 degrees C) of charge-recombination rates between contact radical ion pairs in isopropyl ether. In the systems selected for this study, aromatic hydrocarbon cations are the electron acceptors and the fumaronitrile anion is the electron donor. Nearly quantitative electron transfers occur at all temperatures. The charge recombinations have excess exothermicities of -60 kcal mol(-1) and exhibit a very weak temperature dependence. Our observations emphasize the absence of solvent effects and the relevance of nuclear tunneling in charge recombinations.

Electron transfer in supercritical carbon dioxide: ultraexothermic charge recombination at the end of the "inverted region".

Charge-recombination rates in contact radical-ion pairs, formed between aromatic hydrocarbons and nitriles in supercritical CO(2) and heptane, decrease with the exothermicity of the reactions until they reach -70 kcal mol(-1), but from there on an increase is observed. The first decrease in rate is typical of the "inverted region" of electron-transfer reactions. The change to an increase in the rate for ultra-exothermic electron transfer indicates a new free-energy relationship. We show that the resulting "double-inverted region" is not due to a change in mechanism. It is an intrinsic property of electron-transfer reactions, and it is due to the increase of the reorganisation energy with the reaction exothermicity.

Excited-state proton transfer in gas-expanded liquids: the roles of pressure and composition in supercritical CO2/methanol mixtures.

Excited-state proton transfer from 5,8-dicyano-2-naphthol to methanol takes place in CO2/methanol mixtures, in the pressure and temperature ranges of supercritical CO2. The efficiency of the proton-transfer step decreases with the pressure. This is assigned to the perturbation of the methanol clusters solvating the naphthol.

Absolute rate calculations: atom and proton transfers in hydrogen-bonded systems.

We calculate energy barriers of atom- and proton-transfer reactions in hydrogen-bonded complexes in the gas phase. Our calculations do not involve adjustable parameters and are based on bond-dissociation energies, ionization potentials, electron affinities, bond lengths, and vibration frequencies of the reactive bonds. The calculated barriers are in agreement with experimental data and high-level ab initio calculations. We relate the height of the barrier with the molecular properties of the reactants and complexes. The structure of complexes with strong hydrogen bonds approaches that of the transition state, and substantially reduces the barrier height. We calculate the hydrogen-abstraction rates in H-bonded systems using the transition-state theory with the semiclassical correction for tunneling, and show that they are in excellent agreement with the experimental data. H-bonding leads to an increase in tunneling corrections at room temperature.

Deactivation processes of the lowest excited state of [UO2(H2O)5]2+ in aqueous solution.

A detailed analysis of the photophysical behaviour of uranyl ion in aqueous solutions at room temperature is given using literature data, together with results of new experimental and theoretical studies to see whether the decay mechanism of the lowest excited state involves physical deactivation by energy transfer or a chemical process through hydrogen atom abstraction. Comparison of the radiative lifetimes determined from quantum yield and lifetime data with that obtained from the Einstein relationship strongly suggests that the emitting state is identical to that observed in the lowest energy absorption band. From study of the experimental rate and that calculated theoretically, from deuterium isotope effects and the activation energy for decay support is given to a deactivation mechanism of hydrogen abstraction involving water clusters to give uranium(v) and hydroxyl radicals. Support for hydroxyl radical formation comes from electron spin resonance spectra observed in the presence of the spin traps 5,5-dimethyl-1-pyrroline N-oxide and tert-butyl-N-phenylnitrone and from literature results on photoinduced uranyl oxygen exchange and photoconductivity. It has previously been suggested that the uranyl emission above pH 1.5 may involve an exciplex between excited uranyl ion and uranium(v). Evidence against this mechanism is given on the basis of quenching of uranyl luminescence by uranium(v), together with other kinetic reasoning. No overall photochemical reaction is observed on excitation of aqueous uranyl solutions, and it is suggested that this is mainly due to reoxidation of UO2+ by hydroxyl radicals in a radical pair. An alternative process involving oxidation by molecular oxygen is analysed experimentally and theoretically, and is suggested to be too slow to be a major reoxidation pathway.

Calculation of triplet-triplet energy transfer rates from emission and absorption spectra. The quenching of hemicarcerated triplet biacetyl by aromatic hydrocarbons.

The kinetics of triplet-triplet (T-T) energy transfer have been analysed with a view to linking theories of chemical reactions (involving the rupture and formation of bonds) with theories of processes, such as electron transfer or energy transfer, which preserve chemical bonding. As for the latter, our analysis does not support the claim that, of the two rival expressions for T-T energy transfer, both rooted in the golden rule, only one is applicable to electron transfer or T-T transfer. Though the two expressions do reflect different standpoints, the distinction is eroded by the assumption of a delta-function distribution for the vibrational spectrum. It is shown that theories of chemical reactions also furnish estimates of Franck-Condon factors; rates of chemical reactions and chemical processes are both related to the properties (strengths and lengths) of the reactive bonds, but differ in the mode of energy dissipation. The relationship between the rates of reactions and processes presents new possibilities for a unified view of chemical reactivity.

Absolute rate calculations for atom abstractions by radicals: energetic, structural and electronic factors.

We calculate transition-state energies of atom-transfer reactions from reaction energies, electrophilicity indices, bond lengths, and vibration frequencies of the reactive bonds. Our calculations do not involve adjustable parameters and uncover new patterns of reactivity. The generality of our model is demonstrated comparing the vibrationally adiabatic barriers obtained for 100 hydrogen-atom transfers with the corresponding experimental activation energies, after correction for the heat capacities of reactants and transition state. The rates of half of these reactions are calculated using the Transition-State Theory with the vibrationally adiabatic path of the Intersecting-State Model and the semiclassical correction for tunneling (ISM/scTST). The calculated rates are within an order of magnitude of the experimental ones at room temperature. The temperature dependencies and kinetic isotope effects of selected systems are also in good agreement with the available experimental data. Our model elucidates the roles of the reaction energy, electrophilicity, structural parameters, and tunneling in the reactivity of these systems and can be applied to make quantitative predictions for new systems.