Enhanced Solubility of Ibuprofen by Complexation with ß-Cyclodextrin and Citric Acid.

The ability of ß-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). ß-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (ß-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into ß-CD and then binding the formed ß-CD/IBU inclusion complex with CA. As a result, ternary ß-CD/IBU/CA complex formed by initial incorporation of ibuprofen into ß-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary ß-CD/IBU system. Although the addition of CA to ß-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of ß-CD is significantly less in the ternary complex compared to the binary ß-CD/IBU.

Luminescence of Binary-Doped Silica Aerogel Powders: A Two-Step Sol-Gel Approach.

In this study, we report a novel synthesis of hydrophobic silica aerogel powder composites, functionalized and binary-doped with [Tb(phen)2](NO3)3 and [Eu(phen)2](NO3)3 nanocrystals, employing a two-step sol-gel methodology. The investigation delves into the structural elucidation, optical properties and thermal conductivity of these functionalized Tb(III)-Eu(III) composites. Our analysis includes diffuse reflectance spectra and excitation and luminescence spectra, highlighting the quantum yields of composites with varying chemical compositions. Remarkably, these samples exhibit a strong luminescence, with distinct hues of red or green based on the specific doping type and level. The detailed examination of excitation spectra and quantum yields establishes robust energy-transfer mechanisms from the 1,10-phenanthroline molecule to the lanthanide ions. Notably, our study uncovers a Tb3⁺→Eu3⁺ energy-transfer phenomenon within the binary functionalized samples, providing compelling evidence for a structural formation process occurring within the mesoporous framework of the aerogel powders.

Silica Gels Doped with Gold Nanoparticles: Preparation, Structure and Optical Properties.

A novel, one-pot sol-gel preparation scheme leading to reproducible incorporation of 20-40 nm sized gold nanoparticles (AuNPs) in SiO2 gels is developed based on in situ reduction during gelation using chloroauric acid and ascorbic acid. Variation in the preparation conditions affects the chemical composition, optical properties and size distribution of the AuNPs incorporated in the silica gels. Different organic dopants, i.e., oleic acid, acetic acid or dodecanethiol, are applied to modify the final composite material and to control the rate of reduction and growth of the AuNPs in the gels. The synthesized samples are characterized by UV/Vis/NIR spectroscopy, X-ray diffraction, transmission electron microscopy, thermal conductivity measurements and DTA/TG measurements. The optical properties of the obtained composites are explained using Mie theory. The incorporation of AuNPs leads to an increase in the thermal conductivity of the silica gels. The best process method in this contribution is the use of NaOH as a gelation catalyst and oleic acid as an organic modifier, leading to 20 nm AuNPs dispersed in the silica matrix.

Achieving Complexity at the Bottom: Molecular Metamorphosis Generated by Anthocyanins and Related Compounds.

The concept of molecular metamorphosis is described. A molecule (flavylium cation) generates a sequence of other different molecules by means of external stimuli. The reversibility of the system allows for the flavylium cation to be recovered by other external stimuli, completing one cycle. Differently from supramolecular chemistry, molecular metamorphosis is not a bottom-up approach. All events occur at the bottom. The procedures to characterize the kinetics and thermodynamics of the cycles are summarized. They are based on direct pH jumps (addition of a base to the flavylium cation) and reverse pH jumps (addition of an acid to equilibrated solutions at higher pH values). Stopped flow is an indispensable tool to characterize these systems. The following metamorphic cycles will be described to illustrate the concept: (i) introducing the flavanone in the metamorphic system and illustrating the concept of a timer at the molecular level; (ii) response of the flavylium-based metamorphosis to light inputs and the write-lock-read-unlock-erase molecular system; (iii) a one-way cycle of direct-reverse pH jumps; (iv) interconversion of the flavylium cation with 2,2'-spirobis[chromene] derivatives; (v) 6,8 A-ring substituent rearrangements.

Temperature dependent optical spectroscopy: A study of holmium diphenanthroline nitrate in DMF.

A detailed spectroscopic study of the optical properties of Ho(phen)2(NO3)3 complex is presented. The substance is characterized by UV/Vis spectroscopy, IR - spectroscopy, chemical analysis and X - Ray diffraction. Temperature dependent absorption spectra of Ho(phen)2(NO3)3 in DMF are discussed. A hyperchromic effect at elevated temperatures of the electric dipole absorption transition 5I8→5G6 at 452 nm is observed and a quantitative explanation in the framework of the coth(x) theory of absorption line broadening is suggested. The thermal depopulation of the 5I8 electronic level also is discussed.

Impacts of hydroxylation on the photophysics of chalcones: insights into the relation between the chemical composition and the electronic structure.

A combined theoretical/experimental study of the photoreactivity of two flavylium-derived chalcones, 2,4,4'-trihydroxychalcone and 2,4'-dihydroxychalcone, at the multiconfigurational wavefunction level of theory (CASSCF//CASPT2) in vacuo and in an implicit solvent (water, treated as a polarisable continuum) and by means of linear absorption spectroscopy is presented. The photosensitivity of flavium salts is expressed in the ability of their chalcone form to undergo a cis-trans isomerisation which has found application in logical networks. Despite a considerable amount of experimental data documenting the dependence of the isomerisation on solvent, pH and temperature, the knowledge of how chalcones process energy under various conditions at the molecular level is still scarce. On the example of 2,4,4'-trihydroxychalcone we unravel the complex excited state deactivation mechanism in vacuo involving ultrafast decay through conical intersections, formation of twisted intramolecular charge transfer species, intramolecular proton transfer and inter system crossings. Furthermore, we rationalise the observed discrepancies in the linear absorption spectra of 2,4,4'-trihydroxychalcone and 2,4'-dihydroxychalcone, thereby establishing a link between the functionalisation pattern and the observed spectral properties.

Origin of the metastable stability in flavylium multistate systems.

Metastable states regarding the network of chemical reactions involving flavylium compounds were investigated as well as the role they may play in models for optical memories capable of write-read-erase. A necessary requirement to achieve metastable states in flavylium systems is the existence of a high cis-trans isomerization barrier, as in 4'-hydroxyflavylium described through this paper. In an optical memory, the metastable state could be the signal to be detected upon the write step. In that case the autoerase is prevented by the metastable state. Conversely, the metastable state may be the initial state and prevents the auto and unwanted write step. The compound 4'-hydroxyflavylium offers the possibility of achieving both of these two situations, depending on the sequence of the pH stimuli prior to light absorption. In this work the pH dependent distribution of the flavylium species of the network in the presence of ß-cyclodextrin was calculated. Improvement of the performance of the photochromic system in the presence of ß-cyclodextrin was observed.

Host-Guest Complexes of Flavylium Cations and Cucurbit[7]uril: The Influence of Flavylium Substituents on the Structure and Stability of the Complex.

The host-guest complexes formed from six differently substituted flavylium cations and cucurbit[7]uril (CB7) have been characterized by UV/Vis absorption, fluorescence emission and 1 H NMR spectroscopy. It was observed that all flavylium cations form 1:1 inclusion complexes with association constants that depend on the nature and position of the substituents. The results indicate that CB7 displays higher affinity for more hydrophobic flavylium compounds and for those bearing amino substituents. 1 H NMR spectroscopy was used to elucidate the structure of the complexes. While for 7-hydroxyflavylium and 4-methyl-7-hydroxyflavylium the phenyl group (ring B) is included within the host's cavity leaving the benzopyrilium group (rings A and C) outside, in 4',7-dihydroxyflavylium and 3',4',7-trihydroxyflavylium the macrocycle shuttles between rings A and B. For compounds with amino substituents it was found that CB7 is attracted towards these groups regardless of their position in ring A or B. In addition, it was observed that the dimethylamino group tends to be positioned near the carbonyl-decorated portal while the diethylamino motif prefers the hydrophobic cavity of CB7.

Emptying the ß-cyclodextrin cavity by light: photochemical removal of the trans-chalcone of 4',7-dihydroxyflavylium.

The interaction between the network of chemical reactions of the compound 4',7-dihydroxyflavylium and ß-cyclodextrin was studied by means of pH jumps, followed by UV-vis absorption, flash photolysis, stopped flow, and NMR. The trans-chalcone is the network species exhibiting the strongest interaction with the host. In moderately acidic medium, 95% of the trans-chalcone, 2.5 × 10(-5) M, in the presence of ß-cyclodextrin, 9 × 10(-3) M, is expected to fill the host cavity (association constant 2.2 × 10(3) M(-1)). In contrast, flavylium cation does not interact (association constant ≈ 0). Irradiation of the trans-chalcone in the presence of ß-cyclodextrin 9 mM leads to the flavylium cation appearance. Light is thus capable of removing the trans-chalcone from the ß-cyclodextrin, leaving the cavity empty. The system is reversible and trans-chalcone goes back to the initial state upon switching off the light due to the thermodynamic favorable conversion of flavylium cation to trans-chalcone in the presence of ß-cyclodextrin.

Synthetic analogues of anthocyanins as sensitizers for dye-sensitized solar cells.

Seven flavylium salt dyes were employed for the first time as sensitizers for dye-sensitized solar cells (DSSCs). The theoretical and experimental wavelengths of the maximum absorbances, the HOMO and LUMO energy levels, the coefficients, the oscillator strengths and the dipole moments are calculated for these synthetic dyes. The introduction of a donor group in the flavylium molecular structure was investigated. Photophysical and photoelectrochemical measurements showed that some of these synthetic analogues of anthocyanins are very promising for DSSC applications. The best performance was obtained by a DSSC based on the novel compound 7-(N,N-diethylamino)-3',4'-dihydroxyflavylium which produced a 2.15% solar energy-to-electricity conversion efficiency, under AM 1.5 irradiation (100 mW cm(-2)) with a short-circuit current density (J(sc)) of 12.0 mA cm(-2), a fill factor of 0.5 and an open-circuit voltage (V(oc)) of 0.355 V; its incident photocurrent efficiency of 51% at the peak of the visible absorption band of the dye is remarkable. Our results demonstrated that the substitution of a hydroxylic group with a diethylamine unit in position 7 of ring A of the flavylium backbone expanded the π-conjugation in the dye and thus resulted in a higher absorption in the visible region and is advantageous for effective electron injection from the dye into the conduction band of TiO2.

Thermodynamics, kinetics, and photochromism of oaklins: a recent family of deoxyanthocyanidins.

Two oaklins guaiacylcatechinpyrylium (GCP) and syringylcatechinpyrylium (SCP) and a model compound deoxypeonidin (DOP) were synthesized, and the rate and equilibrium constants of the respective pH dependent network of chemical reactions were calculated. In contrast to anthocyanins, the three compounds possess a small cis-trans isomerization barrier and hence the rate of the trans-chalcone formation follows a bell-shaped curve as a function of pH. The three compounds exhibit photochromism obtained by irradiation of the trans-chalcone, which, depending on pH, leads to the colored species flavylium cation and quinoidal base. The flash photolysis together with pH jumps followed by UV-vis absorption and stopped flow is a very useful tool to achieve the rate and equilibrium constants of the network of chemical reactions followed by these molecules. Oaklin compounds which are formed in wine aged in oak barrels present physical-chemical properties more similar to simpler deoxyanthocyanidins rather than anthocyanins and may play a significant role in color changes observed in wine aging. Given their higher stability, they may be regarded as potential food colorants.

Circular dichroism of anthocyanidin 3-glucoside self-aggregates.

Self-association constants for the flavylium cations of the six most common anthocyanidin 3-glucosides were determined by circular dichroism (CD) and UV-Vis spectroscopy. Along with previous (1)H NMR results, all measurements were consistent with a monomer-dimer model. The CD spectra of the anthocyanidin 3-glucosides were similar to the analogues 3,5-diglucosides. All dimers of the anthocyanidin 3-glucosides exhibited left-handed CD signals, with petunidin-3-glucoside and myrtillin having the most intense signals. In addition, the magnitude of the molar ellipticity, [θ], was generally higher for the 3-glucosides than for the 3,5-diglucosides. For all six anthocyanins studied, the CD absorption spectra of their dimers showed evidence of the splitting of the monomer absorption into lower (J aggregates) and higher (H aggregates) energy bands. The angle and the distance between the dipolar moments of the two monomers comprising the dimer were obtained from the lower energy absorption band. While the angle was more or less similar in all six dimers, the separation distance between the monomer dipole moments differed dramatically. The intensity of the CD signal displayed a linear dependence with the inverse square of the dipole moment distances.

A flash photolysis and stopped-flow spectroscopy study of 3',4'-dihydroxy-7-O-ß-D-glucopyranosyloxyflavylium chloride, an anthocyanin analogue exhibiting efficient photochromic properties.

The complete determination of all rate and equilibrium constants of the network of reversible chemical reactions involving the anthocyanin analogue, 3',4'-dihydroxy-7-O-ß-D-glucopyranosyloxyflavylium chloride, was achieved by means of UV-visible spectroscopy, flash photolysis and pH jumps monitored by stopped-flow. An energy level diagram containing all the data was obtained. A detailed step by step procedure illustrating all the calculations is reported.

The effect of self-aggregation on the determination of the kinetic and thermodynamic constants of the network of chemical reactions in 3-glucoside anthocyanins.

The six most common 3-glucoside anthocyanins, pelargonidin-3-glucoside, peonidin-3-glucoside, delphinidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-glucoside and petunidin-3-glucoside were studied in great detail by NMR, UV-vis absorption and stopped flow. For each anthocyanin, the thermodynamic and kinetic constants of the network of chemical reactions were calculated at different anthocyanin concentration, from 6 × 10⁻6 M up to 8 × 10⁻4 M; an increasing of the flavylium cation acidity constant to give quinoidal base and a decreasing of the flavylium cation hydration constant to give hemiketal were observed by increasing the anthocyanin concentration. These effects are attributed to the self-aggregation of the flavylium cation and quinoidal base, which is stronger in the last case. The UV-vis and ¹H NMR spectral variations resulting from the increasing of the anthocyanin concentration were discussed in terms of two aggregation models; monomer-dimer and isodesmic, the last one considering the formation of higher order aggregates possessing the same aggregation constant of the dimer. The self-aggregation constant of flavylium cation at pH=1.0, calculated by both models increases by increasing the number of methoxy (-OCH3) or hydroxy (-OH) substituents following the order: myrtillin (2 -OH), oenin (2 -OCH3), 3-OGl-petunidin (1 -OH, 1 -OCH3), kuromanin (1 -OH), 3-OGl-peonidin (1 -OCH3) and callistephin (none). Evidence for flavylium aggregates possessing a shape between J and H was achieved, as well as for the formation of higher order aggregates.

Isomerization between 2-(2,4-dihydroxystyryl)-1-benzopyrylium and 7-hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium.

2-Phenyl-1-benzopyrylium (flavylium) and 2-styryl-1-benzopyrylium (styrylflavylium) cations establish in aqueous solution a series of equilibria defining chemical reaction networks responsive to several stimuli (pH, light, redox potential). Control over the mole fraction distribution of species by applying the appropiate stimuli defines a horizontal approach to supramolecular chemistry, in agreement with the customary bottom-up approach toward complex systems. In this work, we designed an asymmetric styrylchalcone able to cyclize in two different ways, producing two isomeric styrylflavylium cations whose chemical reaction networks are thus interconnected. The chemical reaction networks of 2-(2,4-dihydroxystyryl)-1-benzopyrylium (AH(+)) and 7-hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium (AH(+)(iso)) comprise the usual species observed in flavylium-derived networks, in this case, the styryl derivatives of quinoidal bases, hemiketals, and chalcones. The thermodynamics and kinetics of the crossed networks were characterized by the use of UV-vis absorption and NMR spectroscopy as well as time-resolved pH jumps followed by stopped-flow. The two styrylflavylium cations are connected (isomerize) through two alternative intermediates, the asymmetric trans-styrylchalcone (Ct) and a spiropyran-type intermediate (SP). At pH = 1, AH(+) slowly evolves (k(obs) ≈ 10(-5) s(-1)) to a mixture containing 62% AH(+)(iso) through the Ct intermediate, while at pH = 5, the SP intermediate is involved. The observed rate constants for the conversion of the styrylflavylim cations into equilibrium mixtures containing essentially Ct follow a pH-dependent bell-shaped curve in both networks. While at pH = 1 in the dark, AH(+) evolves to an equilibrium mixture containing predominantly AH(+)(iso), irradiation at λ > 435 nm induces the opposite conversion.

Photochemistry of 2-(4-hydroxystyryl)-1-naphthopyrylium.

A new photochromic system based on 2-(4-hydroxystyryl)-1-naphthopyrylium encompasses the properties of the previously described naphthoflavylium and styrylflavylium systems. The photoproduct exhibits a colour deep in hue and is red shifted in comparison with the equivalent flavylium system. Reaction of 2-hydroxy-1-naphthaldehyde with p-hydroxystyrylmethylketone in acetic acid in the presence of tetrafluoroboric acid and acetic anhydride as catalysts leads to a mixture of two compounds: the photochromic 2-(4-hydroxystyryl)-1-naphthopyrylium and a second product 2-(4-acetoxystyryl)-1-naphthopyrylium resulting from the acetylation by acetic anhydride of the former. In acidic medium and at room temperature the hydrolysis of the acetoxy derivative leads to the 2-(4-hydroxystyryl)-1-naphthopyrylium, in circa 2 days, [HCl] = 0.25 M. The pH dependent chemical reactions taking place with 2-(4-hydroxystyryl)-1-naphthopyrylium were determined by UV-Vis, stooped flow, flash photolysis and (1)H NMR and follow the same general pattern of flavylium derivatives. In order to rationalize the photochromism, an energy level diagram summarizing all the equilibrium and rate constants of the network was drawn.

Unidirectional switching between two flavylium reaction networks by the action of alternate stimuli of acid and base.

The introduction of an ester group in the flavylium core allowed the reversible conversion between two different flavylium compounds each one exhibiting its own reaction network. An unidirectional switching cycle between 7-diethylamino-2-(4-(methoxycarbonyl)phenyl)-1-benzopyrylium and 2-(4-carboxyphenyl)-7-diethylamino-1-benzopyrylium was achieved by means of alternate acid and base stimuli. Addition of base to a methanolic solution of the ester derivative gives rise to the trans-chalcone of the parent carboxylic acid, which upon acidification of the solution forms the respective flavylium cation. This species esterifies under very acidic conditions to restore the original methyl ester derivative. The chemical reaction networks of both compounds were fully characterized from their thermodynamic and kinetic aspects, by a series of pH jumps followed by UV-vis absorption and emission spectroscopy, stopped flow and (1)H NMR. The crystal structure of the trans-chalcone of the ester derivative was unveiled showing a supramolecular structure involving hydrogen bonding.

Synthesis and characterization of a symmetric bis(7-hydroxyflavylium) containing a methyl viologen bridge.

A symmetric bis(flavylium) constituted by two 7-hydroxyflavylium moieties linked by a methylviologen bridge was synthesized. The thermodynamic and kinetics of the network of chemical reactions involving bis(flavylium) and the model compound 7-hydroxy-4'-methylflavylium was completely characterized by means of direct and reverse pH jumps (stopped flow) and flash photolysis. Both compounds follow the usual pH-dependent network of chemical reactions of flavylium derivatives. The equilibrium species of the model compound are the flavylium cation (acidic species) and the trans-chalcone (basic species) with an apparent pK'(a)=2.85. In the case of the bis(flavylium) it was possible to characterize by (1)H NMR spectroscopy three species with different degrees of isomerization: all flavylium, flavylium-trans-chalcone, and all trans-chalcone. Representation of the time-dependent mole fraction distribution of these three forms after a pH jump from equilibrated solutions of all-flavylium cation (lower pH values) to higher pH values, shows that formation of trans-chalcone is not completely stochastic (two independent isomerizations), the isomerization of one flavylium showing a small influence on the isomerization of the other. The radical of the methyl viologen bridge is formed upon reduction of the bis(trans-chalcone) with dithionite. The system is reversible after addition of an oxidant in spite of the occurrence of some decomposition.

Chemical behavior of methylpyranomalvidin-3-O-glucoside in aqueous solution studied by NMR and UV-visible spectroscopy.

In the present work, the proton-transfer reactions of the methylpyranomalvidin-3-O-glucoside pigment in water with different pH values was studied by NMR and UV-visible spectroscopies. The results showed four equilibrium forms: the methylpyranomalvidin-3-O-glucoside cation, the neutral quinoidal base, the respective anionic quinoidal base, and a dianionic base unprotonated at the methyl group. According to the NMR data, it seems that for methylpyranomalvidin-3-O-glucoside besides the acid-base equilibrium between the pyranoflavylium cation and the neutral quinoidal base, a new species is formed at pD 4.88-6.10. This is corroborated by the appearance of a new set of signals in the NMR spectrum that may be assigned to the formation of hemiketal/cis-chalcone species to a small extent. The two ionization constants (pK(a1) and pK(a2)) obtained by both methods (NMR and UV-visible) for methylpyranomalvidin-3-O-glucoside are in agreement (pK(a1) = 5.17 ± 0.03; pK(a2) = 8.85 ± 0.08; and pK(a1) = 4.57 ± 0.07; pK(a2) = 8.23 ± 0.04 obtained by NMR and UV-visible spectroscopies, respectively). Moreover, the fully dianionic unprotonated form (at the methyl group) of the methylpyranomalvidin-3-O-glucoside is converted slowly into a new structure that displays a yellow color at basic pH. On the basis of the results obtained through LC-MS and NMR, the proposed structure was found to correspond to the flavonol syringetin-3-glucoside.

Establishment of the chemical equilibria of different types of pyranoanthocyanins in aqueous solutions: evidence for the formation of aggregation in pyranomalvidin-3-O-coumaroylglucoside-(+)-catechin.

The chemical equilibria of the pyranomalvidin-3-glucosides linked to (+)-catechin, (-)-epicatechin, and catechol moieties (and the respective coumaroylglucoside compounds) were established by means of UV-vis spectroscopy. The conjugated double bonds among pyranic rings C and D provide a higher electronic delocalization that prevents the nucleophilic attack of water at position 2. Consequently, besides flavylium cation (AH(+)), the bases A, A(-), and A(2-) have been identified by increasing pH, and the respective acidity constants were determined by spectrophotometry. The formation of dimers at higher concentration was observed for pyranomalvidin-3-O-coumaroylglucoside-(+)-catechin, and the respective data treated by the exciton model suggests the formation of a dimer where the monomers form J-type aggregates with the dipolar moments in opposite directions and rotated by 174° at a distance of 5.2 Å (from the center).