Endogenous Photosensitizers in Human Skin.

Endogenous photosensitizers play a critical role in both beneficial and harmful light-induced transformations in biological systems. Understanding their mode of action is essential for advancing fields such as photomedicine, photoredox catalysis, environmental science, and the development of sun care products. This review offers a comprehensive analysis of endogenous photosensitizers in human skin, investigating the connections between their electronic excitation and the subsequent activation or damage of organic biomolecules. We gather the physicochemical and photochemical properties of key endogenous photosensitizers and examine the relationships between their chemical reactivity, location within the skin, and the primary biochemical events following solar radiation exposure, along with their influence on skin physiology and pathology. An important take-home message of this review is that photosensitization allows visible light and UV-A radiation to have large effects on skin. The analysis presented here unveils potential causes for the continuous increase in global skin cancer cases and emphasizes the limitations of current sun protection approaches.

Red Wine Inspired Chromophores as Photodynamic Therapy Sensitizers.

Hydroxypyranoflavylium (HPF) cations are synthetic analogs possessing the same basic chromophore as the pyranoanthocyanins that form during the maturation of red wine. HPF cations absorb strongly in the visible spectral region, and most are fluorescent, triplet-sensitize singlet oxygen formation in solution and are strong photooxidants, properties that are desirable in a sensitizer for photodynamic therapy (PDT). The results of this study demonstrate that several simple HPF dyes can indeed function as PDT sensitizers. Of the eight HPF cations investigated in this work, four were phototoxic to a human cervical adenocarcinoma cell line (HeLa) at the 1-10 µmol dm-3 level, while only one of the eight compounds showed noticeable cytotoxicity in the dark. Neither a Type I nor a Type II mechanism can adequately rationalize the differences in phototoxicity of the compounds. Colocalization experiments with the most phototoxic compound demonstrated the affinity of the dye for both the mitochondria and lysosomes of HeLa cells. The fact that relatively modest structural differences, e.g., the exchange of an electron-donating substituent for an electron-withdrawing substituent, can cause profound differences in the phototoxicity, together with the relatively facile synthesis of substituted HPF cations, makes them interesting candidates for further evaluation as PDT sensitizers.

Thermodynamics of anion binding to zwitterionic sulfobetaine micelles.

One of the most intriguing aspects of zwitterionic surfactant micelles is their propensity to exhibit selectivity in the binding of the anions of added salts. In this work we examine the thermodynamics of the interaction of the strongly bound perchlorate ion and the more weakly bound bromide ion with micelles of N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (SB3-14) in aqueous solution employing enthalpies derived from isothermal titration calorimetry combined with Gibbs free energies derived from literature data for the binding equilibria. In both cases, the binding is exothermic and enthalpy driven, but entropically unfavorable, with only modest changes in the Gibbs free energy as a function of the extent of anion binding. Likewise, perchlorate ion binding was found to have little or no effect on the aggregation numbers of SB3-14 micelles determined by time-resolved fluorescence quenching of pyrene by the N-hexadecylpyridinium cation. The results are interpreted within the context of the factors involved in the ion-pairing between the anions and the positive charge center of the zwitterion headgroup and the interplay between electrostatics, solvent reorganization and a net loss of translational degrees of freedom that accompany anion binding.

The role of hydrophobicity in supramolecular polymer/surfactant catalysts: An understandable model for enzymatic catalysis.

Enzymes are highly significant catalysts, essential to biological systems, and a source of inspiration for the design of artificial enzymes. Although many models have been developed describing enzymatic catalysis, a deeper understanding of these biocatalysts remains a major challenge. Herein we detail the formation, characterization, performance, and catalytic mechanisms of a series of bio-inspired supramolecular polymer/surfactant complexes acting as artificial enzymes. The supramolecular complexes were characterized and exhibited exceptional catalytic efficiency for the dephosphorylation of an activated phosphate diester, the reaction rate being highly responsive to: (a) pH, (b) surfactant concentration, and (c) the length of the hydrophobic chain of the surfactant. Under optimal conditions (at pH > 8 for the more hydrophobic systems and at pre-micellar concentrations), enzyme-like rate enhancements of up to 6.0 × 109-fold over the rate of the spontaneous hydrolysis reaction in water were verified. The catalytic performance is a consequence of synergy between the hydrophobicity of the aggregates and the catalytic functionalities of the polymer and the catalytic mechanism is modulated by the nature of the hydrophobic pockets of these catalysts, changing from a general base mechanism to a nucleophilic mechanism as the hydrophobicity increases. Taken as a whole, the present results provide fundamental insights, through an understandable model, which are highly relevant to the design of novel bioinspired enzyme surrogates with multifunctional potentialities for future practical applications.

Hybrid Pigments from Anthocyanin Analogues and Synthetic Clay Minerals.

Flavylium cations are synthetic analogues of anthocyanins, the natural plant pigments that are responsible for the majority of the red, blue, and purple colors of flowers, fruits, and leaves. Unlike anthocyanins, the properties and reactivity of flavylium cations can be manipulated by the nature and position of substituents on the flavylium cation chromophore. Currently, the most promising strategies for stabilizing the color of anthocyanins and flavylium cations appear to be to intercalate and/or adsorb them on solid surfaces and/or in confined spaces. We report here that hybrid pigments with improved thermal stability, fluorescence, and attractive colors are produced by the cation-exchange-mediated adsorption of flavylium cations (FL) on two synthetic clays, the mica-montmorillonite SYn-1, and the laponite SYnL-1. Compared to the FL/SYn-1 hybrid pigments, the FL/SYnL-1 pigments exhibited improved thermal stability as judged by color retention, better preferential adsorption of the cationic form of FL1 at neutral to mildly basic pH (pH 7-8), and lower susceptibility to color changes at pH 10. Although both clays adsorb the cationic form on their external surfaces, SYnL-1 gave more evidence of adsorption in the interlayer regions of the clay. This interlayer adsorption appears to be the contributing factor to the better properties of the FL/SYnL-1 hybrid pigments, pointing to this clay to be a promising inorganic matrix for the development of brightly colored, thermally more stable hybrid pigments based on cationic analogues of natural plant pigments.

Conical intersections and the weak fluorescence of betalains.

Betalains are natural plant pigments found in certain plants belonging to the order Caryophyllales. This work presents theoretical calculations on the excited state properties of three betalains: betanin, an almost non-fluorescent natural betacyanin; indicaxanthin, a weakly fluorescent natural betaxanthin; and cBeet120, a synthetic betaxanthin fluorescence probe that is also weakly fluorescent. Calculations at the algebraic diagrammatic construction (ADC (2)) level of theory, combined with the conductor-like screening model (COSMO) to simulate solvent effects, predict absorption spectra in good agreement with experiment for all three of these betalains. Several distinct theoretical approaches identify torsions of the molecular geometry that can lead to conical intersections between the excited singlet (S1) and ground state (S0) potential surfaces and identify probable geometries at the minimum on the crossing seam (MXS). The present results thus emphasize the central role played by torsional modes in determining the fluorescence properties of natural betalains and of most synthetic betalain analogs as well. A direct implication of the results is that the fluorescence quantum yields of natural or synthetic betalains can potentially be enhanced by introducing structural modifications that permit the molecule to avoid these MXS geometries and/or by incorporation into a more rigid environment that hinders the specific bond rotations involved in the non-radiative relaxation of the excited state.

Photoacidity of the 7-Hydroxyflavylium Cation.

Theoretical descriptions of excited state proton transfer (ESPT) have had various degrees of success. This work presents a theoretical description of the photodissociation of the 7-hydroxyflavylium cation (7-HF), the fundamental chromophoric moiety of anthocyanin natural plant pigments. ESPT of 7-HF is promoted by a significant shift of charge away from the OH group in the first singlet excited state, leading smoothly to the excited conjugate base and a protonated water cluster. Several factors contribute to the consistency of the results of the present study: (1) the theoretical approach (TD-DFT with the B3-LYP functional and def2-TZVP basis set utilizing Grimme's D3 dispersion correction); (2) the modeling of the solvent effect combining hydrogen bonding of the photoacid to a cluster of discrete water molecules in a water-like continuum solvent (COSMO); (3) the large S1 -S2 energy gap of flavylium cations; and (4) the electrostatics of the ESPT in which a proton is transferred from a cationic photoacid to water without Coulombic interaction between the proton and the conjugate base.

Highly fluorescent hybrid pigments from anthocyanin- and red wine pyranoanthocyanin-analogs adsorbed on sepiolite clay.

Flavylium cations serve as models for the chemical and photochemical reactivity of anthocyanins, the natural plant pigment responsible for many of the red, blue and purple colors of fruits and flowers. Likewise, pyranoflavylium cations serve as models of the fundamental chromophoric moiety of pyranoanthocyanins, molecules that can form from reactions of grape anthocyanins in red wines during their maturation. In the present work, hybrid pigments are prepared by the adsorption of a series of five synthetic flavylium cations (FL) and five synthetic pyranoflavylium cations (PFL) on sepiolite clay (SEP). The FL are smaller in size than the PFL, but both can in principle fit into the tunnels and/or external grooves (with dimensions of 3.7 × 10.6 Å) of SEP. Measurements of the fluorescence quantum yields of the adsorbed dyes indicate that they are at least as fluorescent as in acidic acetonitrile solution, and in a few cases substantially more fluorescent. The observation of biexponential fluorescence decays is consistent with emission from dye molecules adsorbed at two distinct sites, presumably tunnels and grooves. These hybrid materials also have improved properties in terms of stability of the color in contact with pH 10 aqueous solution and resistance to thermal degradation of the dye. SEP thus appears to be a promising substrate for the development of highly fluorescent flavylium or pyranoflavylium cation-derived hybrid pigments with improved color and thermal stability.

The electronic transitions of analogs of red wine pyranoanthocyanin pigments.

There is increasing interest in using natural colorants like anthocyanins in cosmetics, food and pharmaceuticals as replacements for synthetic colorants. During the maturation of red wines, the anthocyanin pigments contained in grapes are transformed via reaction with copigments and metabolic products into pyranoanthocyanins, responsible in part for the final color of the wine. In order to understand structural effects on the absorption spectra of pyranoanthocyanins, the calculated excited state energies and spectroscopic states of a series of substitued pyranoflavylium cation analogs of pyranoanthocyanins have been compared to experimental spectroscopic data for these compounds. The vertical excitation energies, calculated by using the ADC(2) approach, gave excellent agreement with the experimental UV-Vis spectra and the nature of the lowest excited state correlates with the observed photophysical behavior in solution. The present results thus provide a basis for the design of new pyranoflavylium chromophores with the desired colors and photophysics, as well as for understanding the analogous properties of natural pyranoanthocyanin pigments in red wine.

Triplet Excited States and Singlet Oxygen Production by Analogs of Red Wine Pyranoanthocyanins.

During the maturation of red wines, the anthocyanins of grapes are transformed into pyranoanthocyanins, which possess a pyranoflavylium cation as their basic chromophore. Photophysical properties of the singlet and triplet excited states of a series of synthetic pyranoflavylium cations were determined at room temperature in acetonitrile solution acidified with 0.10 mol dm-3 trifluoroacetic acid (TFA, to inhibit competitive excited state proton transfer) and at 77 K in a rigid TFA-acidified isopropanol glass. In solution, the triplet states of these pyranoflavylium cations are efficiently quenched by molecular oxygen, resulting in sensitized formation of singlet oxygen, as confirmed by direct detection of the triplet-state decay by laser flash photolysis and of singlet oxygen monomol emission in the near infrared. The strong visible light absorption, the relatively small singlet-triplet energy differences, the excited state redox potentials and the reasonably long lifetimes of pyranoflavylium triplet states in the absence of molecular oxygen suggest that they might be useful as triplet sensitizers and/or as cationic redox initiators in polar aprotic solvents like acetonitrile.

Ground- and Excited-State Acidity of Analogs of Red Wine Pyranoanthocyanins.

Pyranoflavylium cations are synthetic analogs containing the same basic chromophore as the pyranoanthocyanins that form in red wine during maturation and are responsible for its final color. Determination of the ground- and excited-state acidities for a series of eight substituted hydroxy pyranoflavylium cations shows that they are weak acids in the ground state (pKa ranging from 3.4 to 4.4 in aqueous buffer solution), but substantially more acidic in the first excited singlet state (pKa * ranging from ca. 0.2 to 0.7 in 30% methanol-water). Unlike the ground-state acidities, which show no obvious trend with electronic effects of the substituents, the excited-state pKa * values correlate well with Hammett sigma parameters for the substituents on the pyranoflavylium chromophore. This difference in the transmission of electronic effects between ground and excited state is reflected in the localization of the HOMO of the cation and conjugate base in distinct regions of the chromophore as compared to delocalization of the LUMO over the entire molecule. The current results provide further support for the conclusion that excited-state proton transfer is the dominant deactivation pathway for the pyranoflavylium cation excited singlet state in aqueous or aqueous-organic media and presumably for pyranoanthocyanins as well.

Chemistry Inspired by the Colors of Fruits, Flowers and Wine.

An overview is provided of the status of research at the frontiers of investigation of the chemistry and photochemistry of two classes of natural plant pigments, the anthocyanins and the betalains, as well as of the pyranoanthocyanin pigments formed from anthocyanins during the maturation of red wine. Together, anthocyanins and betalains are responsible for almost all of the red, purple and blue colors of fruits and flowers and anthocyanins and pyranoanthocyanins are major contributors to the color of red wines. All three types of pigments are cationic below about pH 3, highly colored, non-toxic, reasonably soluble in water or alcohol and fairly stable to light. They exhibit good antioxidant or antiradical activity and, as part of our diet, confer a number of important health benefits. Systematic studies of model compounds containing the basic chromophoric groups of these three types of pigments are providing a deeper understanding of the often complex chemistry and photochemistry of these pigments and their relationship to the roles in vivo of these pigments in plants. These natural pigments are currently being exploited as starting materials for the preparation of novel semi-synthetic dyes, pigments and fluorescence probes.

Improved Synthesis of Analogues of Red Wine Pyranoanthocyanin Pigments.

An improved procedure is described for the preparation of pyranoflavylium cations from the reaction of 5,7-dihydroxy-4-methylflavylium cation with aromatic aldehydes. Modifications of the procedure of Chassaing et al. (Tetrahedron Lett. 2008, 49, 6999-7004; Tetrahedron 2015, 71, 3066-3078) circumvent the reported restriction to electron-rich benzaldehydes and provide access to a wide variety of substituted pyranoflavylium cations, including those with electron-withdrawing substituents or an attached heterocyclic or polycyclic aromatic ring. This opens the way for studies of substituent and structural effects on the ground and excited states of these pyranoanthocyanin analogues, the behavior of which should mirror fundamental aspects of the chemistry and photophysics of the pyranoanthocyanin chromophores present in mature red wines.

How Do Amides Affect the Electronic Properties of Pyrene?

The electronic properties of amide linkers, which are intricate components of biomolecules, offer a wealth of unexplored possibilities. Herein, we demonstrate how the different modes of attaching an amide to a pyrene chromophore affect the electrochemical and optical properties of the chromophore. Thus, although they cause minimal spectral shifts, amide substituents can improve either the electron-accepting or electron-donating capabilities of pyrene. Specifically, inversion of the amide orientation shifts the reduction potentials by 200 mV. These trends indicate that, although amides affect to a similar extent the energies of the ground and singlet excited states of pyrene, the effects on the doublet states of its radical ions are distinctly different. This behavior reflects the unusually strong orientation dependence of the resonance effects of amide substituents, which should extend to amide substituents on other types of chromophores in general. These results represent an example where the Hammett sigma constants fail to predict substituent effects on electrochemical properties. On the other hand, Swain-Lupton parameters are found to be in good agreement with the observed trends. Examination of the frontier orbitals of the pyrene derivatives and their components reveals the underlying reason for the observed amide effects on the electronic properties of this polycyclic aromatic hydrocarbon and points to key molecular-design strategies for electronic and energy-conversion systems.

Chemistry Inspired by the Colors of Fruits, Flowers and Wine

ABSTRACT An overview is provided of the status of research at the frontiers of investigation of the chemistry and photochemistry of two classes of natural plant pigments, the anthocyanins and the betalains, as well as of the pyranoanthocyanin pigments formed from anthocyanins during the maturation of red wine. Together, anthocyanins and betalains are responsible for almost all of the red, purple and blue colors of fruits and flowers and anthocyanins and pyranoanthocyanins are major contributors to the color of red wines. All three types of pigments are cationic below about pH 3, highly colored, non-toxic, reasonably soluble in water or alcohol and fairly stable to light. They exhibit good antioxidant or antiradical activity and, as part of our diet, confer a number of important health benefits. Systematic studies of model compounds containing the basic chromophoric groups of these three types of pigments are providing a deeper understanding of the often complex chemistry and photochemistry of these pigments and their relationship to the roles in vivo of these pigments in plants. These natural pigments are currently being exploited as starting materials for the preparation of novel semi-synthetic dyes, pigments and fluorescence probes.

Correction: Cucurbit[7]uril inclusion complexation as a supramolecular strategy for color stabilization of anthocyanin model compounds.

Correction for 'Cucurbit[7]uril inclusion complexation as a supramolecular strategy for color stabilization of anthocyanin model compounds' by Barbara Held, et al., Photochem. Photobiol. Sci., 2016, DOI: 10.1039/c6pp00060f.

Cucurbit[7]uril inclusion complexation as a supramolecular strategy for color stabilization of anthocyanin model compounds.

Host-guest complexation with cucurbit[7]uril of anthocyanin model compounds in which acid-base equilibria are blocked resulted in essentially complete stabilization of their color. The color protection is a thermodynamic effect and establishes a strategy to stabilize these colored compounds at pH values of interest for practical applications.

Kinetic studies of the reaction between pesticides and hydroxyl radical generated by laser flash photolysis.

BACKGROUND: Due to contamination of the environment by pesticides and their mishandling, there is the need for treatment of contaminated sites and correct disposal of materials containing them. Thus, studies with advanced oxidation processes are expanding and can determine the rate constant of the hydroxyl radical with organic compounds of great importance in environmental contamination. In this context, the use of laser flash photolysis has been shown to be viable for the determination of these constants. RESULTS: The reaction rate constants of different pesticides with HO(•) in degassed acetonitrile have been determined. They were 1.6 × 10(9) M(-1) s(-1), 0.6 × 10(9) M(-1) s(-1), 1.2 × 10(9) M(-1) s(-1), 2.4 × 10(9) M(-1) s(-1) and 2.2 × 10(9) M(-1) s(-1) for the pesticides carbaryl, propoxur, fenoxycarb, ethoxysulfuron and chlorimuron-ethyl, respectively. These values are about an order of magnitude smaller than the diffusion controlled rate and correlate with the relative rates of disappearance of the pesticides in the photo-Fenton reaction in water. CONCLUSION: The correlation of the relative rate constants determined by laser flash photolysis with the relative rates of photo-Fenton degradation of the pesticides is compelling evidence for the participation of the hydroxyl radical in the degradation of these pesticides in the latter system.