Solubilization and Photostabilization in a Sodium Deoxycholate Hydrogel of a Neutral Conjugated Thiophene Oligomer and Polymer.

Oligo(3-hexylthiophene-co-1,4-phenylene) and poly(3-hexylthiophene) were solubilized in sodium deoxycholate self-assemblies in water solutions and hydrogels, with the goal of solubilizing sufficient material in a hydrogel for fluorescence applications. The neutral conjugated oligomer and polymer were incorporated as monomers into the self-assemblies with sodium deoxycholate aggregates, leading to the photoprotection of these neutral conjugated and water-insoluble molecules. Dynamic light scattering, rheology, and fluorescence experiments established that the deoxycholate aggregation and gel formation properties were not altered with the incorporation of the oligomer or polymer into the deoxycholate self-assemblies, showing that this adaptable host system with some molecular recognition elements is a viable strategy to incorporate into hydrogels neutral conjugated molecules as isolated monomers. This strategy has the potential to be used when conjugated molecules are used for fluorescence applications in hydrogels.

Dynamics of small molecules within the F127 PEO-PPO-PEO triblock copolymer gel and sol phases studied at the molecular scale.

Triplet excited states of guest molecules with different hydrophobicities were used to probe the association and dissociation dynamics of these guests with F127 micelles in the gel and sol phases. The dynamics probed was on a longer length scale than amenable with fluorescence techniques, but at a shorter length scale than probed in translational diffusion studies. The mobility of the guests at the molecular scale showed that subtle changes in the guest's structure affect the guest's release time from the micelles, where the structural features of the guest are more important than the phase, gel vs. sol, of the system.

Mechanism of a Disassembly-Driven Sensing System Studied by Stopped-Flow Kinetics.

We carried out steady-state and stopped-flow photophysical measurements to determine the kinetics of a discrete disassembly driven turn-on fluorescent system. On and off rates for both DimerDye1 assembly and nicotine binding were determined. Relative rates for these competing processes provide insight on how this system can be optimized for sensing applications. Kinetics studies in artificial saliva showed that moving to more complex media has minimal effects on the sensing ability of the system.

Nonlinear Dependence on Na+ Ions for the Binding Dynamics of Cucurbit[6]uril with the trans-1-Methyl-4-(4-hydroxystyryl)pyridinium Cation.

The binding dynamics of the trans-1-methyl-4-(4-hydroxystyryl)pyridinium cation (HSP+) to cucurbit[6]uril (CB[6]) in the presence of Na+ cations were studied to establish the effect of the relative concentrations of the system's components (HSP+, CB[6], and Na+) on these dynamics. The formation of the HSP+@CB[6] complex was temporally uncoupled from the photoisomerization of trans-HSP+, while a nonlinear effect of the Na+ cation concentration on the HSP+@CB[6] dynamics was observed. This nonlinearity is a consequence of Na+ having the opposite effect on the association and dissociation rate constants for the HSP+@CB[6] complex, creating a conceptual framework for using such nonlinearities to control multistep reactions in cucurbit[n]uril chemistry.

Labeling of Proteins by BODIPY-Quinone Methides Utilizing Anti-Kasha Photochemistry.

A novel approach for the photolabeling of proteins by a BODIPY fluorophore is reported that is based on an anti-Kasha photochemical reaction from an upper singlet excited state (Sn) leading to the deamination of the BODIPY quinone methide precursor. On the other hand, the high photochemical stability of the dye upon excitation by visible light to S1 allows for the selective fluorescence detection from the dye or dye-protein adduct, without concomitant bleaching or hydrolysis of the protein-dye adduct. Therefore, photolabeling and fluorescence monitoring can be uncoupled by using different excitation wavelengths. Combined theoretical and experimental studies by preparative irradiations, fluorescence, and laser flash photolysis fully disclose the photophysical properties of the dye and its anti-Kasha photochemical reactivity. The application of the dye was demonstrated on photolabeling of bovine serum albumin.

Photoelimination of nitrogen from adamantane and pentacycloundecane (PCU) diazirines: a spectroscopic study and supramolecular control.

Photochemical reactivity of pentacycloundecane (PCU) and adamantane diazirines was investigated by preparative irradiation in different solvents, laser flash photolysis (LFP) and quantum chemical computations. In addition, formation of inclusion complexes for diazirines with cucurbit[7]uril, ß- and γ-cyclodextrin (ß- and γ-CD) was investigated by 1H NMR spectroscopy, isothermal microcalorimetry and circular dichroism spectroscopy, followed by the investigation of photochemical reactivity of the formed complexes. Diazirines undergo efficient photochemical elimination of nitrogen (ΦR > 0.5) and deliver the corresponding singlet carbenes. Singlet carbenes react in intra- and intermolecular reactions and we found a rare singlet carbene pathway in CH3OH involving protonation and formation of a carbocation, detected due to the specific rearrangement of the pentacycloundecane skeleton. Singlet diazirines undergo intersystem crossing and deliver triplet carbenes that react with oxygen to form ketones which were isolated after irradiation. Our main finding is that the formation of diazirine inclusion complexes with ß-CD and γ-CD changes the relative ratio of singlet vs. triplet pathways, with singlet carbene products being dominant from the chemistry of the irradiated complexes. Our combined theoretical and experimental studies provide new insights into the supramolecular control of carbene reactivity which has possible applications for the control of product distribution by solvent effects and the choice of constrained media.

Noninnocent Role of Na+ Ions in the Binding of the N-Phenyl-2-naphthylammonium Cation as a Ditopic Guest with Cucurbit[7]uril.

Na+ ions influence the mechanism for the binding of the ditopic guest N-phenyl-2-naphthylammonium cation (Ph-AH+-Np) to cucurbit[7]uril (CB[7]) by facilitating, at increased Na+ concentrations, the formation of a higher-order complex. Binding of the larger naphthyl moiety of Ph-AH+-Np forms the Ph-AH+-Np@CB[7] 1:1 complex (where "@" represents an inclusion complex) at low Na+ ion concentrations (≤5 mM), whereas the inclusion of the smaller phenyl moiety in CB[7] (CB[7]@Ph-AH+-Np) is transient. Ph-AH+-Np@CB[7] is formed by reactions with free CB[7] and CB[7]·Na+ (where "·" represents an exclusion complex) with displacement of the Na+ cation. Because of the latter reaction, the dissociation of Ph-AH+-Np@CB[7] is faster at higher Na+ concentrations. At high Na+ concentrations (≥25 mM), the Na+ ion stabilizes the inclusion of the phenyl moiety in CB[7] by capping the portal of CB[7]. The dynamics of the capped Na+·CB[7]@Ph-AH+-Np 1:1 complex is slower than in the absence of Na+ capping. This stabilization of the phenyl moiety inclusion in CB[7] by Na+ leads to the formation of the Na+·CB[7]@Ph-AH+-Np@CB[7] 2:1 host-guest complex, where each moiety of the ditopic guest is included in a different CB[7]. The opposing roles of Na+ cations in the formation of the two 1:1 complexes are essential for the switch in mechanism with changes in Na+ concentration and provide an example of systems chemistry, where new properties arise in the form of an increased diversity of complexes and altered complexation dynamics that depend on the system's composition.

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.

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.

Steric Demand and Rate-determining Step for Photoenolization of Di-ortho-substituted Acetophenone Derivatives.

Laser flash photolysis of ketone 1 in argon-saturated methanol yields triplet biradical 1BR (τ = 63 ns) that intersystem crosses to form photoenols Z-1P (λmax = 350 nm, τ ~ 10 µs) and E-1P (λmax = 350 nm, τ > 6 ms). The activation barrier for Z-1P re-forming ketone 1 through a 1,5-H shift was determined as 7.7 ± 0.3 kcal mol-1 . In contrast, for ketone 2, which has a less sterically hindered carbonyl moiety, laser flash photolysis in argon-saturated methanol revealed the formation of biradical 2BR (λmax = 330 nm, τ ~ 303 ns) that intersystem crosses to form photoenol E-2P (λmax = 350 nm, τ > 42 µs), but photoenol Z-2P was not detected. However, in more viscous basic H-bond acceptor (BHA) solvent, such as hexamethylphosphoramide, triplet 2BR intersystem crosses to form both Z-2P (λmax = 370 nm, τ ~ 1.5 µs) and E-2P. Thus, laser flash photolysis of ketone 2 in methanol reveals that intersystem crossing from 2BR to form Z-2P is slower than the 1,5-H shift of Z-2P, whereas in viscous BHA solvents, the 1,5-H shift becomes slower than the intersystem crossing from 2BR to Z-2P. Density functional theory and coupled cluster calculations were performed to support the reaction mechanisms for photoenolization of ketones 1 and 2.

Photodeamination to quinone methides in cucurbit[n]urils: potential application in drug delivery.

We demonstrate a proof of principle for a new approach in the development of a drug delivery system. A positively charged prodrug (phenol) can form a stable inclusion complex with CB[7], which enables more efficient delivery of the prodrug. After photochemical transformation (photoactivation) inside the complex, an active drug quinone methide (QM) is formed and released from the complex, since it is a neutral molecule and forms a less stable complex with CB[7].

Protein capped nanosilver free radical oxidation: role of biomolecule capping on nanoparticle colloidal stability and protein oxidation.

We studied the effect of human serum albumin protein capped spherical nanosilver on the nanoparticle stability upon peroxyl radical oxidation. The nanoparticle-protein composite is less prone to oxidation compared to the individual components. However, higher concentrations of hydrogen peroxide were formed in the nanoparticle-protein system.

Probing the Microenvironments in a Polymer-Wrapped Core-Shell Nanoassembly Using Pyrene Chromophores.

The local environments within an amphiphilic polymer shell wrapped around lanthanide-doped upconverting nanoparticles were probed using steady-state and time-resolved fluorescence spectroscopy techniques. Emission lifetime measurements of pyrene chromophores trapped within the polymer shell reveal that there are at least two environments, where the organic pyrene molecules are encapsulated in hydrophobic environments that have lower polarity than in water. The migration of pyrene chromophores from their initial location to another location was also observed, demonstrating that the polymeric shell provides both hydrophobicity and mobility for entrapped molecules. These results offer insight into what outcomes can be expected when chemical reactions are carried out in these nanoassemblies, especially if they are to be used as nanoreactors for synthesis or delivery vehicles for therapeutics.

Hydroxymethylaniline Photocages for Carboxylic Acids and Alcohols.

ortho-, meta- and para-Hydroxymethylaniline methyl ethers 3-5-OMe and acetyl derivatives 3-5-OAc were investigated as potential photocages for alcohols and carboxylic acids, respectively. The measurements of photohydrolysis efficiency showed that the decaging from ortho- and meta-derivatives takes place efficiently in aqueous solution, but not for the para-derivatives. Contrary to previous reports, we show that the meta-derivatives are better photocages for alcohols, whereas ortho-derivatives are better protective groups for carboxylic acids. The observed differences were fully disclosed by mechanistic studies involving fluorescence measurements and laser flash photolysis (LFP). Photoheterolysis for the para-derivatives does not take place, whereas both meta- and ortho-derivatives undergo heterolysis and afford the corresponding carbocations 3-C and 4-C. The ortho-carbocation 4-o-C was detected by LFP in aqueous solution (λmax = 410 nm, τ ≈ 90 µs). Moreover, spectroscopic measurements for the meta-acetyl derivative 3-m-OAC indicated the formation of cation in the excited state. The application of an ortho-aniline derivative as a protective group was demonstrated by synthesizing several derivatives of carboxylic acids. In all cases, the photochemical deprotection was accomplished in high yields (>80%). This mechanistic study fully rationalized the photochemistry of aniline photocages which is important for the design of new photocages and has potential for synthetic, biological, and medicinal applications.

Photochemical Formation of Anthracene Quinone Methide Derivatives.

Anthrols 2-7 were synthesized and their photochemical reactivity investigated by irradiations in aq CH3OH. Upon excitation with visible light (λ > 400 nm) in methanolic solutions, they undergo photodehydration or photodeamination and deliver methyl ethers, most probably via quinone methides (QMs), with methanolysis quantum efficiencies ΦR = 0.02-0.3. Photophysical properties of 2-7 were determined by steady-state fluorescence and time-correlated single photon counting. Generally, anthrols 2-7 are highly fluorescent in aprotic solvents (ΦF = 0.5-0.9), whereas in aqueous solutions the fluorescence is quenched due to excited-state proton transfer (ESPT) to solvent. The exception is amine 4 that undergoes excited-state intramolecular proton transfer (ESIPT) in neat CH3CN where photodeamination is probably coupled to ESIPT. Photodehydration may take place via ESIPT (or ESPT) that is coupled to dehydration or via a hitherto undisclosed pathway that involves photoionization and deprotonation of radical cation, followed by homolytic cleavage of the alcohol OH group from the phenoxyl radical. QMs were detected by laser flash photolysis and their reactivity with nucleophiles investigated. Biological investigation of 2-5 on human cancer cell lines showed enhancement of antiproliferative effect upon exposure of cells to irradiation by visible light, probably due to formation of electrophilic species such as QMs.

Tuning the Binding Dynamics of a Guest-Octaacid Capsule through Noncovalent Anchoring.

Hydrophobic or hydrophilic substituents have different effects on the binding dynamics of pyrene derivatives with a 2:1 capsule formed from two octaacid cavitands, showing a subtle interplay of different kinetic factors. Anchoring of the methyl group of 1-methylpyrene within one cavitand slowed the association and dissociation dynamics of the 1:1 complex by at least 1000 times when compared to the 1:1 complex for pyrene. This slow down for the transient formation of the 1:1 complex is responsible for the overall increase in stability of the 2:1 complex without affecting the overall capsule dissociation. For 1-pyrenemethanol, its residence time in the 2:1 capsule is shorter compared to that of pyrene despite both guests having similar equilibrium constants for the binding of the second cavitand, suggesting that the hydroxymethyl substituent close to the equatorial region of the capsule can interact with water during the partial opening of the capsule.

Photochemical behavior of biosupramolecular assemblies of photosensitizers, cucurbit[n]urils and albumins.

Biosupramolecular assemblies combining cucurbit[n]urils (CB[n]s) and proteins for the targeted delivery of drugs have the potential to improve the photoactivity of photosensitizers used in the photodynamic therapy of cancer. Understanding the complexity of these systems and how it affects the properties of photosensitizers is the focus of this work. We used acridine orange (AO+) as a model photosensitizer and compared it with methylene blue (MB+) and a cationic porphyrin (TMPyP4+). Encapsulation of the photosensitizers into CB[n]s (n = 7, 8) modified their photoactivity. In particular, for AO+, the photo-oxidation of HSA was enhanced in the presence of CB[7]; meanwhile it was decreased when included into CB[8]. Accordingly, peroxide generation and protein fragmentation were also increased when AO+ was encapsulated into CB[7]. The triplet excited state lifetimes of all the photosensitizers were lengthened by their encapsulation into CB[n]s, while the singlet oxygen quantum yield was enhanced only for AO+ and TMPyP4+, but it decreased for MB+. The results obtained in this work prompt the necessity of further investigating these kinds of hybrid assemblies as drug delivery systems because of their possible applications in biomedicine.