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The kinetics, thermodynamics, and degradation of malvidin mono- and diglucosides were studied following a holistic approach by extending to the basic medium. In acidic conditions, the reversible kinetics of the flavylium cation toward the equilibrium is controlled by the hydration and cis - trans isomerization steps, while in the basic medium, the OH - nucleophilic addition to the anionic quinoidal bases is the slowest step. There is a pH range (transition pHs), between the acidic and basic paradigms, that includes physiological pH (7.4), where degradation reactions occur faster, preventing the system from reaching the equilibrium. The transition pH of the diglucoside is narrower, and in contrast with the monoglucoside, there is no evidence for the formation of colored oligomers among the degradation products. Noteworthy, OH - addition in position 4 to form B4 2- , a kinetic product that decreases the overall equilibration rate, was observed only for the diglucoside.

The kinetics and thermodynamics of the pH-dependent reversible and irreversible processes leading to color fading of pelargonidin-3- O -glucoside, peonidin-3- O -glucoside, malvidin-3- O -glucoside, and cyanidin-3- O -glucoside dyes in aqueous solutions are reported. Following the addition of base to the flavylium cation, the quinoidal bases disappear by three distinct steps: (i) in an acidic medium by a biexponential process, in which the faster step is controlled by the hydration reaction and the slower one by cis-trans isomerization; the degradation process occurs essentially from the anionic quinoidal base; (ii) in a basic medium (pH > 9.5), in which the disappearance of the anionic bases is monoexponential, with the rate proportional to the hydroxyl concentration (hydroxyl attack), leading to anionic chalcones ( cis and trans ) at equilibrium─the slower degradation step occurs from the di- and trianionic chalcones; and (iii) in the pH region circa 7.7 < pH < 9.5, in which hydration and hydroxyl attacks are much slower than anionic quinoidal base degradation (which is the rate-controlling step) and the equilibrium cannot be attained.

Flavylium compounds are a well-known family of pigments because they are prevalent in the plant kingdom, contributing to colors over a wide range from shades of yellow-red to blue in fruits, flowers, leaves, and other plant parts. Flavylium compounds include a large variety of natural compound classes, namely, anthocyanins, 3-deoxyanthocyanidins, auronidins, and their respective aglycones as well as anthocyanin-derived pigments (e.g., pyranoanthocyanins, anthocyanin-flavan-3-ol dimers). During the past few decades, there has been increasing interest among chemists in synthesizing different flavylium compounds that mimic natural structures but with different substitution patterns that present a variety of spectroscopic characteristics in view of their applications in different industrial fields. This Review provides an overview of the chemistry of flavylium-based compounds, in particular, the synthetic and enzymatic approaches and mechanisms reported in the literature for obtaining different classes of pigments, their physical-chemical properties in relation to their pH-dependent equilibria network, and their chemical and enzymatic degradation. The development of flavylium-based systems is also described throughout this Review for emergent applications to explore some of the physical-chemical properties of the multistate of species generated by these compounds.

While identified by the respective flavylium cation, anthocyanins are much more than this molecule. The flavylium cation (generally appearing only at very acidic pH values) is one of the molecules of a complex sequence of pH dependent molecular species reversibly interconnected by different chemical reactions. These species include the red flavylium cation, purple quinoidal base and blue or bluish anionic quinoidal bases. At the common pH of the vacuoles of simpler anthocyanins, the red flavylium cation is present only at very acidic pH values and at moderately acidic pHs there is no significant colour of the purple quinoidal base. Moreover, the blue or bluish anionic quinoidal base appearing around neutral pH values is not stable. Intermolecular (copigmentation) and intramolecular (in acylated anthocyanins) interactions increase the colour hue and yield bathochromic shifts in the absorption bands, permitting to extend the pH domain of the flavylium cation and increase the mole fraction of the quinoidal bases. Metal complexation is another strategy. In particular, the Al 3+ cation plays an essential role in the blue colour of hydrangea. The most sophisticated structures are however the metaloanthocyanins, such as the one that gives the blue colour of commelina communis , constituted of six anthocyanins, six flavanones and two metals. In this work we discuss how physical chemical tools are indispensable to account for the chemical behaviour of these complex systems. The experimental procedures and the equations needed to calculate all equilibrium constants of anthocyanins and the consequent pH dependent mole fraction distributions in the absence or presence of copigments are described in detail. Reverse pH jumps monitored by stopped flow have been shown to be an indispensable tool to calculate these parameters.

Anthocyanins are the basis of the color of angiosperms, 3-deoxyanthocyanins and sphagnorubin play the same role in mosses and ferns, and auronidins are responsible for the color in liverworts. In this study, the color system of cyanidin-3- O -glucoside (kuromanin) as a representative compound of simpler anthocyanins was fully characterized by stopped flow. This type of anthocyanin cannot confer significant color to plants without intra- or intermolecular interactions, complexation with metals or supramolecular structures as in Commelina communis. The anthocyanin's color system was compared with those of 3-deoxyanthocyanins and riccionidin A, the aglycone of auronidins. The three systems follow the same sequence of chemical reactions, but the respective thermodynamics and kinetics are dramatically different.

Anthocyanins co-pigmentation models with application on 1:1 complexes were revisited, and their limitations were critically commented. The flavylium multistate of species is dramatically simplified to a single acid-base equilibrium between flavylium cation and its conjugated base CB, equal to the sum of quinoidal base, hemiketal, and cis and trans -chalcones. Bearing this, a new equation that simultaneously allows calculation of the co-pigmentation constant with flavylium cation ( K AH + CP ) and with its conjugated base CB ( K CBCP ) was deduced. This equation can be used at a fixed co-pigment concentration with pH as a variable or at fixed pH and co-pigment concentration variable. A global fitting of all data allows us to calculate both association constants with good accuracy. The model was applied to the co-pigmentation of malvidin-3-glucoside with caffeine and pentagalloyl glucose (PGG). Caffeine gives rise to complexes not only with flavylium cation K AH + CP = 125 ± 7 M -1 but also with CB with K CBCP = 23 ± 3 M -1 . PGG complexes exclusively with flavylium cation, K AH + CP = 914 ± 10 M -1 , and the possible interaction with quinoidal base is lower than the detection limits that the inherent experimental error permits.

The kinetics and thermodynamics (in acidic solutions) of the five chemical species reversibly interconnected by external stimuli (a multistate), such as pH and light, generated by the liverworts colorant riccionidin A were investigated. The degradation products of the multistate formed after 10 days at neutral pH were identified. The behaviour of riccionidin A multistate was compared with previous results reported for the equivalent systems based on 3-deoxyanthocyanidins (found in mosses and ferns) and anthocyanins (ubiquitous in angiosperms). The five chemical species have mutatis mutandis similar structures in the three multistates. The most dramatic difference is the extremely slow interconversion rate between flavylium cation and trans-chalcone in riccionidin A and related compounds multistates (tens of days) when compared with deoxyanthocyanins (a few days) and anthocyanins (several hours), at room temperature. The mole fraction distribution of the five species that constitute the multistate as a function of pH is also different in the three families of compounds. Some considerations regarding the chemical evolution of the three systems are given., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Two anthocyanins from purple-fleshed sweet potato were isolated and characterized by LC-MS and NMR analysis. They were identified as peonidin-3-(6'-hydroxybenzoyl)-sophoroside-5-glucoside and peonidin-3-(6'-hydroxybenzoyl-6″-caffeoyl)-sophoroside-5-glucoside. The acid-base dynamics of these acylated anthocyanins was evaluated by means of pH jump techniques. Equilibrium and kinetic constants were determined and, in general, these anthocyanins demonstrated a higher capacity in retaining the red and blue colors at acidic and basic pH values, suggesting a higher resistance to pH variations compared to the parent anthocyanin, peonidin-3-O-glucoside. The presence of acyl groups and additional glucoside moieties seems to determine this particular characteristic. The fluorescence properties of these anthocyanins were evaluated. Overall, the species present at higher pH values (7-9) showed higher fluorescence intensity for both anthocyanins, with an optimum λ ex /λ em pair at λ ex 610 nm/λ em 640 nm. The fluorescence characteristics of these anthocyanins were used to evaluate their location in gastric and intestinal cells by fluorescence microscopy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The interaction of malvidin-3- O-glucoside (1) and a lignosulfonate was studied by UV-visible spectroscopy, and the results obtained showed the formation of a complex between the negatively charged lignosulfonate and the flavylium cation form (AH + ) of this anthocyanin at pH 1. The thermodynamic and kinetic parameters of 1 in the presence of a lignosulfonate were determined by UV-visible spectroscopy and stopped-flow techniques. The main differences were observed in the flavylium cation (AH + )/quinoidal base (A) equilibrium, the AH + form being more stabilized than A (p K a1 = 4.4 ± 0.1) compared with 1 in the absence of the lignosulfonate (p K a1 = 3.9 ± 0.1). Furthermore, comparing the hydration ( k h = 0.028 s -1 ) and dehydration ( k -h = 40 M -1 s -1 ) processes of 1 in the presence of the lignosulfonate with the processes of 1 ( k h = 0.12 s -1 and k -h = 35 M -1 s -1 ) show that the hydration process is slower while the dehydration process is practically unaffected in the presence of the lignosulfonate.

All equilibrium and rate constants of heavenly blue anthocyanin (HBA 1) as well as the derivatives with two (HBA 2) or none (HBA 3) acylated units were determined. The three acylated units of the sugar in position 3 of the peonidin chromophore of HBA 1 are essential to confer the peculiar stability of its purple and blue colors. The sugars generate an efficient protective environment around position 2 (and 4) of the flavylium cation, through an intramolecular sandwich-type stacking that retards 35-fold the hydration reaction ( k h ) and increases 8.8-fold the dehydration reaction ( k -h ), when compared with the peonidin chromophore HBA 3. The conjugation of these two rates lowers 308-fold the hydration equilibrium constant ( K h ), corresponding to a raise of the energy level of the hemiketal by 14.2 kJ mol -1 . Conversely, the p K a of the quinoidal base in HBA 1 is only slightly stabilized in comparison with that of HBA 2 and HBA 3. The energy level of hemiketal increases with the number of acylated units, but the inversion of energies between hemiketal and quinoidal base takes place exclusively for HBA 1 (three acylated units), permitting in moderately acidic solutions the stabilization of the purple quinoidal base. Identical inversion of energy was observed for the corresponding ionized species, allowing the stabilization of the blue ionized quinoidal base in slightly basic solutions. At pH values higher than 8, the hydroxyl groups of the hydroxycinnamic acid units start to deprotonate disrupting the intramolecular sandwich-type stacking and the more or less slow degradation of the anthocyanin is observed.

Anthocyanins are identified by the respective flavylium cation, which is only one species of a multistate of different molecules reversibly interconverted by external inputs such as pH, light and temperature. The flavylium cation (acidic form) is involved in an apparent acid-base reaction, where the basic species is the sum of quinoidal base, hemiketal and cis - and trans -chalcones, their relative fraction depending on the substitution pattern of the flavylium cation. The full comprehension of this complex system requires a thermodynamic and kinetic approach. The first consists in drawing an energy level diagram where the relative positions of the different species are represented as a function of pH. On the other hand, the kinetic approach allows measuring the rates of the reactions that interconnect reversibly the multistate species. The kinetics is greatly dependent on the existence or not of a high cis - trans isomerization barrier. In this work, the procedure to obtain the energy level diagram and the rates of inter-conversion in the multistate in both cases (low or high isomerization barrier) are described. Practical examples of this approach are presented to illustrate the theory, and recently reported applications based on host-guest complexes are reviewed.

Copigmentation and the anti-copigmentation effects can be mimicked by the interaction of anthocyanin's model compounds respectively with cucurbit[7]uril (CB7) and β-cyclodextrin (β-CD). The complex network of chemical reactions displayed by this family of compounds includes the colored flavylium cation, AH(+), and quinoidal base, A, along with the colorless hemiketal, B, cis-chalcone, Cc, and trans-chalcone, Ct. Whereas AH(+) is stable only at very acidic pH values, the remaining species are formed at slightly acidic and neutral conditions. However, under these conditions, for most of the natural and synthetic flavylium salts, the colorless species predominate (B, Cc, and Ct) at the expense of A. The host CB7 was found to improve the color of solutions in two different ways: first, it stabilizes AH(+) at higher pH values by decreasing its acidity and, second, it enhances the mole fraction of A due to selective complexation of this species in the pH range where the flavylium cation is no longer stable. In contrast, β-CD increases the acidity of AH(+), favoring the formation of Ct at the expense of all the other multistate species (Bası́lio et al. New J. Chem. 2013, 37, 3166-3173; Petrov et al. J. Phys. Chem. A 2013, 117, 10692-10701; Gago et al. Dyes Pigments 2014, 110, 106-112; and Lopes-Costa et al. Photochem. Photobiol. Sci. 2014, 13, 1420-1426). Although both hosts have a large effect on the hydration rate and pH domain of the flavylium cation, the effect on the degradation kinetics of anthocyanidins is modest. CB7 decreases the hydration rate and decreases the acid-base (AH(+)/A) equilibrium constant (Ka), leading respectively to a slowing and a speeding of the anthocyanin degradation rate. On the other hand, β-CD increases the hydration rate but increases Ka, both effects acting in opposite directions.

The determination of rate and equilibrium constants of anthocyanin metabolites with in vivo occurrence, cyanidin-4'-O-methyl-3-glucoside (Cy4'Me3glc) and cyanidin-7-O-glucuronyl-3-glucoside (Cy7Gluc3glc), was carried out for the first time by means of direct and reverse pH jumps. The thermodynamics and kinetics of these compounds are similar to the anthocyanin monoglucosides in particular for the analogous cyanidin-3-glucoside (Cy3glc) and peonidin-3-glucoside (Peo3glc). The rate and equilibrium constants of metabolites were also compared with malvin (malvidin 3,5-diglucoside) and with a bioinspired compound 3',4'-dihydroxy-7-O-glucopyranosyloxyflavylium (DGF). In Cy4'Me3glc and Cy7Gluc3glc the rate of hydration for a fixed pH value is slower than in DGF and the dominant species at moderately acidic solutions is the hemiketal. Oppositely, in DGF trans-chalcone is the dominant species at moderately acidic solutions.

The kinetics and thermodynamics of the 2,6-bis(2-hydroxybenzilidene)cyclohexanone chemical reactions network was studied at different pH values using NMR, UV-vis, continuous irradiation, and flash photolysis. The chemical behavior of the system partially resembles anthocyanins and their analogue compounds. 2,6-Bis(2-hydroxybenzilidene)cyclohexanone exhibits a slow color change from yellow to red styrylflavylium under extreme acidic conditions. The rate constant for this process (5 × 10(-5) s(-1)) is pH independent and controlled by the cis-trans isomerization barrier. However, the interesting feature is the appearance of the colorless compound, 7,8-dihydro-6H-chromeno[3,2-d]xanthene, isolated from solutions of acid to neutral range, characterized by (1)H NMR and single crystal X-ray diffraction. Light absorption by 2,6-bis(2-hydroxybenzilidene)cyclohexanone solutions immediately after preparation exclusively results in cis-isomer as photoproduct, which via hemiketal formation yields (i) red styrylflavylium by dehydration under extremely acidic solutions (pH < 1) and (ii) colorless 7,8-dihydro-6H-chromeno[3,2-d]xanthene by cyclization in solutions of acid to neutral range.

Independently of the natural or synthetic origin, flavylium derivatives follow the same network of chemical reactions. Actually, the flavylium cation is stable only at low pH values. Increasing the pH gives rise to the formation of several species: quinoidal bases, hemiketal, cis- and trans-chalcones, and their deprotonated forms. A deep knowledge of the thermodynamics and kinetics of these species is an essential tool to practical applications of these compounds, in particular, in the domain of food chemistry. In this work the network of chemical reactions involving flavylium derivatives is presented, and the respective thermodynamics and kinetics are discussed in detail, including the mathematical expressions and a step-by-step procedure to calculate all of the rate and equilibrium constants of the system. Examples of systems possessing a high or low cis-trans isomerization barrier are shown. Recent practical applications of anthocyanins and related compounds illustrate the potentialities of the flavylium-based family of compounds.

During red wine maturation in contact with oak wood, C-glucosidic ellagitannins can react with anthocyanins, leading to new pigments. In this work the thermodynamic and kinetic constants of the network pH-dependent equilibrium of a new myrtillin (delphinidin 3-O-glucoside)-vescalagin hybrid pigment (1-deoxyvescalagin-(1β→8)-myrtillin) have been determined by UV-visible absorption and stopped-flow experiments and compared to those determined for myrtillin. The vescalagin substitution at the C-8' center of myrtillin entails important variations in the pigment behavior upon pH changes. The hybrid pigment showed lower pK'a and pKa values and a much higher value of Kt. As a consequence, at moderately acidic pH values (4 < pH < 6), the percentage of the hemiketal is much lower and the quinoidal base and the (E)-chalcone represent higher percentages relative to those for myrtillin. Therefore, the hybrid pigment can provide in slightly acidic or neutral solutions an exceptionally different color compared to that of myrtillin.

The multiequilibrium system of reactions of cyanidin 3-glucoside at acidic and mildly acidic pH values was studied in the presence of caffeine as a copigment. The thermodynamic and kinetic constants were determined using the so-called direct and reverse pH jump experiments that were followed by conventional UV-vis spectroscopy or stopped flow coupled to a UV-vis detector, depending on the rate of the monitored process. Compared with that of free anthocyanin, the copigmentation with caffeine extends the domain of the flavylium cation up to less acidic pH values, while in a moderately acidic medium, the quinoidal base becomes more stabilized. As a consequence, the hydration to give the colorless hemiketal is difficult over the entire range of pH values. At pH 1, two adducts were found for the flavylium cation-caffeine interaction, with stoichiometries of 1:1 and 1:2 and association constants of 161 M⁻¹ (K₁) and 21 M⁻¹ (K₂), respectively.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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-β-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.

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.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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).

The compound 7,4'-dihydroxy-5-methoxyflavylium (dracoflavylium) was identified as the major red colorant in samples of the resin "dragon's blood", extracted from the tree Dracaena draco. The complex network of reversible chemical reactions that dracoflavylium undergoes in aqueous solution is fully described; for the first time, all the equilibrium constants that enable a complete characterisation of the system have been obtained (K'(a)=1.6 x 10(-4), K(a1)=1.0 x 10(-4), K(a2)=3.2 x 10(-8), K(Ct1)=1.0 x 10(-7), K(Ct2)=1.3 x 10(-10)). It is concluded that the red colour is due to a stable quinoid base, A, which is the major species at pH 4-7. It is further shown that this compound does not fit the commonly accepted definitions of anthocyanidin nor 3-deoxyanthocyanidin. Similarly to synthetic flavylium salts, the natural compound 7,4'-dihydroxy-5-methoxyflavylium gives rise to several species (multistate system) reversibly interconverted by external stimuli, such as pH.

Anthocyanins and related flavylium derivatives exist in aqueous solution as a pH-dependent mole fraction distribution of species (a multistate system) with known biological activity. Introduction of nitrogen heterocycles in the flavylium core can lead to multistates with different constitution and increased activity. Compound 1, a diethylamino derivative of 4-pyridinechalcone, was synthesized and characterized by X-ray crystallography, showing a pH-dependent reaction network similar to anthocyanins and related compounds. The several species present at the equilibrium multistate were fully characterized by 1H NMR and 13C NMR. The thermodynamics and kinetics of the multistate were studied through pH jumps followed by 1H NMR and UV-vis absorption including stopped-flow for the faster kinetic steps. In the parent 4-pyridinechalcone compound, protonation of the pyridine nitrogen for pH < 4 prevents formation of the flavylium cation. In compound 1, the first protonation takes place in the diethylamino substituent and in acidic medium, two new flavylium derivatives, a single (2 < pH < 4) and a double (pH < 1) positively charged species, in equilibrium with protonated hemiketal, cis and trans chalcones, have been characterized. Differently from anthocyanins and related compounds, experimental evidence for an unexpected very slow (0.0003 s−1) ring opening-closure between the hemiketal and the cis-chalcone (tautomerization) was achieved. [ABSTRACT FROM AUTHOR]

Anthocyanins lipophilization recently emerged as an efficient tool to deliver oil-soluble dyes aiming to expand their applications in lipophilic matrices such as cosmetics formulations. Sodium dodecyl sulfate (SDS) micelles were used to solubilize malvidin-3-glucoside derivatives bearing an ester chain derived from dodecanoic and hexanoic fatty acids. Detailed investigations on the kinetic and thermodynamic behavior of the pigments towards pH variations was carried out by means of UV-Vis spectroscopy. It was found that the pH domain of the red flavylium cation is extended in ca 0.3–0.4 pH units. The mole fraction of the quinoidal base at neutral conditions increased by 40% when compared with malvidin-3-glucoside in the same micellar media, which provides a great blue color stabilization. The results presented herein report for the first time the blue color stabilization of these lipophilic anthocyanin bioactives, opening new application fields as novel colorants for lipid-based foods and cosmetics. [ABSTRACT FROM AUTHOR]

Blue was the last color to be spread in Nature by the anthocyanins present in angiosperms, and the last color to be managed by Humans in Anthropocene. Blue also appears in a small number of algae, fungi, and bacteria, but these living beings have very little to do with the profusion of a natural blue hue. Humanity took many long years to figure out how to reproduce and use blue - the classic example of which is indigo dye, extracted from plants like the Indigofera tinctoria. However, even simple anthocyanins are not capable of achieving blue. Plants had to develop strategies to fix this color, mainly by intramolecular copigmentation in acylated anthocyanins and complexation with metals, as in metalloanthocyanins. Blue was absent in the first paleolithic cave paintings. Those depictions were made using reds, yellows, and blacks of all hues, but no blue. In addition, blue LEDs and LASERs came later after red and green. It was only at the end of the 20th century that genetic engineering was able to create blue flowers adapted to the markets to meet consumer demands. Food and beverage producers continue to look for a natural blue as an alternative to synthetic colorants. Blue remained a second-rate color in the West for a long time. Despite that fact, in many countries blue is now the preferred color. In this review we track the appearance of blue in Nature and in the Anthropocene. [Display omitted] • Simple anthocyanins are unable to confer blue color. • While ubiquitous the blue was a color that the human beings reproduced, made and mastered difficultly and tardily. • Blue is the last color to be diffused in Nature and in many applications and discoveries by Humans in Anthropocene. [ABSTRACT FROM AUTHOR]

The rearrangement between isomers 6- and 8-bromo-apigeninidin ( 6 and 8) was studied by pH jumps using stopped flow, UV/Vis, NMR, and HPLC analysis. The system constitutes a pH-dependent network of chemical reactions involving up to 18 different species. The dynamic network is equivalent to a single diprotic acid exhibiting two p Kas, 2.55 and 5.4. Similar to other flavylium derivatives, the mole fraction of the species hemiketal and cis-chalcone in both multistate isomers are negligible at the equilibrium. At pH 1, the pure isomers are slowly converted in a mixture containing about 50 % of isomers 6 and 8, while at pH 4, the system evolves to mixture of 10 % trans-chalcone and 90 % of quinoidal bases. A series of pH jumps from pure isomer 6 at pH 1 to pH 6 and back to pH 1 leads to the same initial absorption spectra of the pure isomer 6. The same occurs for pure isomer 8, showing the lack of communication between the cis-chalcones, at least in the time scale of few minutes. A pH jump from the equilibrated mixture of the isomers at pH 1.0 to 5.8 permits to follow a very slow isomerization. [ABSTRACT FROM AUTHOR]

Anthocyanins are much more than flavylium cation. At least four other species in moderately acidic solutions are formed constituting a pH reversible network of chemical reactions. The study of this network is an indispensable tool to rationalize the colour as well as the reactivity of these molecules. The network of anthocyanins was revisited and the one of related compounds, such as vitisins, described in detail. The colour given by anthocyanins is function of their concentration due to self-aggregation as well as by the possibility of co-pigmentation with other wine components. These phenomena can only be fully understood if the thermodynamic and kinetics of anthocyanins and related compounds are known. In aged red wines, vitisins nicely illustrate the evolution of anthocyanins. These compounds result from the chemical reaction of anthocyanins with other wine components and are very resistant to the hydration lacking the colourless hemiketals formation. This indicates that less colorant is necessary to confer colour to the wine and also explains the colour change from the red-violet in young wines to the red-orange observed in aged wines. [ABSTRACT FROM AUTHOR]

Abstract: The network of chemical reactions involving anthocyanins and related compounds has been historically considered as the chemical transformations taking place when the flavylium cation (which is generally stable only in very acidic solutions) disappears upon a pH jump to higher pH values (direct pH jump). In this work profit is taken from the appearance of flavylium cation from equilibrated solutions at moderately acid pH values, (reverse pH jumps) as well as upon irradiation of trans-chalcone in the cases where photochemistry is available. Reverse pH jumps, flash photolysis and reaction quantum yields unequivocally show that at sufficiently acidic pH values the tautomerization becomes the rate determining step of flavylium cation formation. This is a lucky situation since gives kinetic information about tautomerization, the most difficult process to access in the anthocyanins and related compounds network of chemical reactions. The thermodynamic and kinetic details of flavylium base photochromic systems are described. Mathematical expressions for direct and reverse pH jumps, stopped flow and flash photolysis are presented as well as the procedure to obtain all of the rate and equilibrium constants of the system. [Copyright &y& Elsevier]

The pH dependence of the network of chemical reactions involving 3′,4′,7-trihydroxyflavylium was studied and all the rate and equilibrium constants were determined in the presence and absence of β-cyclodextrin. The β-cyclodextrin increases the rate constant of the flavylium cation hydration to give the hemiketal and decreases the reverse rate constant (de-hydration). The quantum yield of the flavylium cation formation from irradiation of the trans-chalcone increases from 0.023 to 0.055, respectively, in the absence and presence of β-cyclodextrin. NMR spectral characterization of the inclusion complex between 3′,4′,7-trihydroxyflavylium and β-cyclodextrin was performed by ROESY and suggests a structure in which the hydroxyl substituents at positions 3′ and 4′ interact with the internal surface of the β-cyclodextrin. [ABSTRACT FROM AUTHOR]

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 1H 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. [ABSTRACT FROM AUTHOR]

Abstract: Flavylium is the basic structure of anthocyanins, an important family of natural dyes responsible for the color in many flowers and fruits. While anthocyanins in vitro are involved in a pH dependent equilibrium between a flavylium cation (acidic species) and a hemiketal (as major basic species), some synthetic flavylium compounds present the trans-chalcone as the major basic species. In this case irradiation of the trans-chalcone leads to appearance of colored products, either a flavylium cation and/or a quinoidal base, via cis-chalcone and hemiketal. Taking profit from the complexity of the network it is possible to design photochromic systems, exhibiting a thermal back reaction, or models for optical memories, when the back reaction is prevented. The flavylium photochromism was also observed in ionic liquids, gels, micelles and reversed micelles opening up possible applications. In this work an overview of the photochromism of synthetic flavylium compounds is presented, from the first observations of the light effect to recent developments. [Copyright &y& Elsevier]

A complete resolution of time evolution for all species of flavylium chemical reactions network in acidic to neutral media was obtained applying Laplace transform methods, Vieta’s formulae and the general partial fraction theorem. Analyses of particular systems under direct pH-jump, reverse pH-jump, stopped flow and flash photolysis experiments have been performed. The deduced formulas cover all possibilities of flavylium and anthocyanins compounds—with or without quinoidal base and with or without cis–trans isomerization barrier. The expressions for the observed rate constants in different type of experiments are quite similar. This allows creation of global procedure, based on fitting of one single set of expressions with data-set from different experiments. The mathematical approach allows easy and versatile programming. [ABSTRACT FROM AUTHOR]

Flavylium-based compounds in their acidic and cationic form bring color to aqueous solutions, while under slightly acidic or neutral conditions they commonly bring discoloration. Selective host-guest complexation between water-soluble p-sulfonatocalix[n]arenes (SCn) macrocycles and the flavylium cationic species can increase the stability of the colored form, expanding its domain over the pH scale. The association constants between SCn and the cationic (acid) and neutral basic forms of flavylium-based compounds were determined through UV-Vis host-guest titrations at different pH values. The affinity of the hosts for synthetic chromophore was found to be higher than for a natural anthocyanin (Oenin). The higher affinity of SC4 for the synthetic flavylium was confirmed by 1H NMR showing a preferential interaction of the flavylium phenyl ring with the host cavity. In contrast with its synthetic counterpart, the flavylium substitution pattern in the anthocyanin seems to limit the inclusion of the guest in the host's binding pocket. In this case, the higher affinity was observed for the octamer (SC8) likely due to its larger cavity and higher number of negatively charged sulfonate groups. [ABSTRACT FROM AUTHOR]

The multistate system of 4′,7-dihydroxy-3-methoxyflavylium is constituted by a multiequilibrium involving trans-chalcone, cis-chalcone, hemiketal, flavylium cation and quinoidal base. This system possesses two independently addressable inter-connected photochromic systems based on the cis–trans isomerization and ring opening-closure of the hemiketal. [ABSTRACT FROM AUTHOR]

• Photochromic system in water based on 5OH4′NMe2 in the presence of SDS micelles. • Photochemical response leading to a good colour contrast in an extended range of pH. • Photochromism based on stable and long-life meta-stable states. The multistate of species originated by the compound 5-hydroxy-4′-dimethylaminoflavylium was studied in the presence of sodium dodecyl sulfate micelles 0.1 M. A series of pH jumps obtained by addition of base to the equilibrated solutions of the flavylium cation results in a metastable equilibrium between the flavylium cation and the quinoidal base with p K a = 7.6. In neutral to moderately basic medium, only at 60 °C and after 5 days a new distribution involving the flavylium cation and trans -chalcones is achieved. On the other hand, the anionic trans -chalcone can be formed in few minutes in very basic medium at room temperature and from this, another meta-stable state constituted by protonated, neutral and anionic trans -chalcones, p K Ct+/Ct = 2.6 and p K Ct/Ct- = 10.7 is reached. The equilibrium is apparently attained between flavylium cation, neutral and anionic trans -chalcones respectively for p K AH+/Ct = 4.1 and p K Ct/Ct- = 10.7. Irradiation of the neutral (stable or metastable) and protonated (meta-stable) trans -chalcones yields to the appearance of the quinoidal base or the flavylium cation in an extended pH region 1 < pH < 10. The peculiar properties of this flavylium based photochromic system are explained by means of an energy level diagram where cis -chalcone and hemiketal lay above the quinoidal base. [ABSTRACT FROM AUTHOR]

Abstract The thermodynamic and kinetic behavior of 4-(2,4-dihydroxybenzylidene)-6-hydroxy-1,2,3,4-tetrahydroxanthylium chloride was studied in detail. Similarly to anthocyanins, this compound generates a multistate of species that are reversibly interconverted by pH stimuli. The multistate system was studied by NMR and UV–visible (conventional spectroscopy and stopped-flow techniques). A theoretical approach adapted from the one reported for anthocyanins and related compounds was used to rationalize the complex multistate. In particular, the thermodynamic diagram where all the species are positioned was extended to the ionized species. Cis and trans isomers of flavylium cation, quinoidal bases, and ionized chalcone at extremely high pH values were identified. The multistate is dominated in the range 5 < pH < 8 by the spiro form in equilibrium with a small fraction of quinoidal bases. The spiro opening rates follow a different route and pH dependence in very acidic or moderately acidic pHs. Graphical abstract Image 1 Highlights • 2,6-bis(2-hydroxybenzylidene)cyclohexanones follow the general anthocyanins multistate of species. • A thermodynamic and kinetic model adapted from the one reported for anthocyanins and related compounds, was used to rationalize the complex multistate data for 4-(2,4-dihydroxybenzylidene)-6-hydroxy-1,2,3,4-tetrahydroxanthylium chloride. • A spiro derivative is the species that differentiates the present system from anthocyanins. It was fully characterized by NMR and is the dominant species in the pH range 5

The multistate of species regarding 2′-hydroxyflavylium derivatives have a peculiar behavior due to the formation in moderately basic solutions of a flavanone from the mono-ionized trans -chalcone. The firmly established theory to account for the thermodynamics and kinetics of the flavylium based multistate of species in acidic medium was extended to the basic medium. The key experimental procedure to carry out this study is a sequence of reverse pH jumps from all pH range to a final pH sufficiently acid to have flavylium cation as the sole species. The reverse pH jumps can be performed from the equilibrium and pseudo-equilibrium. Acidification of the flavanone to pH = 1 does not give back flavylium cation. In contrast, the di-ionized species tran s-chalcone is obtained in a very fast process from the flavanone at pH > 12. A cycle constituted by a sequence of pH jumps illustrates the concept of a timer at the molecular level with reset capacity. [ABSTRACT FROM AUTHOR]

The impact of a lignosulfonate (calcium) ( L ) on the chromatic features of two anthocyanin-derived bluish dyes (portisin, P and pyranoanthocyanin dimer, PD ) was evaluated in aqueous solutions using UV–Visible spectroscopy. It was demonstrated that the interaction between each dye and this macromolecule at pH 1 occurs by two mechanisms, association and copigmentation that are dependent on L concentration. For instance, at low concentrations of L (up to 0.27 μM) it is observed the association of dyes promoted by their complexation with lignin (different molecules of dye are bound to the same binding sites of L ). At higher concentrations of L (25 μM), the aggregation of dyes decreases and each molecule is bound to a different site of L resulting in the formation of a charge-transfer complex (copigmentation). Moreover, the titration of both dyes ( P and PD ) in the presence of L (19 μM) showed a strong stabilization of their pyranoflavylium cation forms revealed by the considerably higher pK a1 (6.6 ± 0.1 and 6.2 ± 0.1 for P and PD , respectively) in the presence of this macromolecule when compared to the values obtained in the absence (pK a1  = 4.61 ± 0.03 and 4.93 ± 0.04). In addition, the water solubility of the dyes in the absence and presence of L was also evaluated by turbidimetry and the results showed that the water soluble lignosulfonate improved the solubility of the dyes over time. [ABSTRACT FROM AUTHOR]

[Display omitted] • trans -Chalcones derived from 2-phenyl-1-benzopyrylium cations exist in solution as multistate systems involving several species. • trans -n-Pyridinechalcones (n=2′,3′,4′) exhibit similar multistate systems with slower kinetics and where flavylium is absent. • Both types of chalcones undergo photoisomerization and/or photo-ring closure reactions depending on pH. • Depending on the solvent, trans -2′-pyridinechalcone may give rise to new compounds in the multistate. • The new compounds were fully characterized and pave the way to applications in photochromism and biological applications. The kinetics and thermodynamics of the pH-dependent multistate of species generated by the trans -chalcone of n-pyridinebenzopyrylium (n = 2′, 3′) were studied by UV–vis spectroscopy, 1H NMR and HPLC-MS, and the results compared with those reported for n = 4′. Due to the slow kinetics of the multistate species interconversion, the conjugation of these techniques has shown to be a powerful tool to investigate the behaviour of these systems. The species involved in the multistate are mutatis mutandis the same observed in anthocyanins and related compounds except for the flavylium cation, which was not observed in these systems even in very acidic medium. The rates of the interconversion of the multistate species upon pH stimuli are much slower than in anthocyanins. The compound bearing the pyridine nitrogen in position 2′ gives two novel products absorbing in the visible. Formation of the new products is particularly efficient from the thermal evolution of the photochemical products obtained upon light irradiation of the protonated trans -chalcone in a mixture of methanol:acidic water (1:1). This confirms the unique capacity of the substituents in position 2′ in giving intramolecular reactions involving the benzopyrylium core. Crystal structures for the three pyridine chalcone compounds (n = 2′, 3′, 4′) were obtained and the respective structures discussed. [ABSTRACT FROM AUTHOR]

The host-guest chemistry of the anthocyanin analog 7- β -D-glucopyranosyloxy-4′-hydroxyflavylium (GHF) was studied in the presence of the β -cyclodextrin derivative captisol by stopped flow, UV–visible spectroscopy, flash photolysis, circular dichroism and isothermal titration calorimetry. The equilibrium and rate constants of the multistate of chemical species derived from the flavylium ion were calculated and compared with those in the absence of the host. A new procedure to obtain the host-guest association constants of the multistate (including the transient species) by superimposing the two energy level diagrams, in the presence and absence of the cyclodextrin, was developed. The results indicate that the magnitude of the association constants follows the order, trans -chalcone ≈ cis -chalcone ≈ hemiketal > quinoidal base > flavylium cation. The hydration equilibrium constant increases ca. 42 times in the presence of captisol as the hydration and dehydration rate constants respectively increases and decreases. The other equilibrium constants are modestly affected: the rate constants of ring closure and opening are significantly decreased in the complex and the isomerization rate constants increase in both directions. The quantum yield of the photochromic system in the presence of captisol is 0.3, i.e. 3 times higher than in the absence of the host. [ABSTRACT FROM AUTHOR]

The equilibrium forms of three different families of dimethylamino-based pyranoanthocyanins ( 1 , 2 and 3 ) were studied in aqueous solutions at different pH values from 1 to 12 using UV–Visible spectroscopy. The forms present under those conditions are strongly correlated to the pyranoanthocyanin structural features. The increase of the electronic delocalization helps the protonation at the amino group. At very acidic pH condition (pH < 0) the protonation at the amino group is observed for the three pigments, but under less acidic conditions (pH∼1) it only occurs for pigment 3 (pK a1 = 2.4 ± 0.1) and at a lesser extent for pigment 2 (pK a1 = 1.1 ± 0.1). At the same time, the increase of the electronic delocalization on the amino-based pigments also favors the deprotonation at the hydroxyl group present at carbon C-7 yielding the neutral quinoidal base (pK a2 = 2.7 ± 0.1, pK a2 = 4.8 ± 0.1 and pK a2 = 5.4 ± 0.1 for pigment 3 , 2 and 1 , respectively). For pigment 3 , the maximum molar fraction obtained for the pyranoflavylium cation form is ∼0.4 due to the proximity of the two acid-base constants (pK a1 and pK a2 ) which indicates that at the pH range 1–5 three forms of the compound are present in equilibrium (pyranoflavylium dication, pyranoflavylium cation and neutral quinoidal base). The second deprotonation at the 4′-OH was less affected by the structural features of the pigment with the ionization constant situated at pK a3 ∼9 (pK a3 = 9.5 ± 0.1, pK a3 = 8.9 ± 0.1 and pK a3 = 9.8 ± 0.1 for pigment 1 , 2 and 3 , respectively). [ABSTRACT FROM AUTHOR]

The network of chemical reactions of the compound 4′-(2-hydroxyethoxy)-7-hydroxyflavylium and its photochromic properties were studied in the absence and presence of β -cyclodextrin. The system was characterized by 1 H NMR, UV–Vis, continuous irradiation and circular dichroism. In the presence of β -cyclodextrin 4.8 mM the p K ′ a is reduced to 2.2. The association constants with β -cyclodextrin, follow the order trans -chalcone > quinoidal base > flavylium cation , respectively 1.7 × 10 3 M −1 ; 5.6 × 10 2 M −1 ; ≈0. The rate of inter-conversion of the network species increases in the presence of β -cyclodextrin circa 2.6 times. The appearance of an induced circular dichroism signal of trans -chalcone inside the β -cyclodextrin is described for the first time. It gives information about the position of the guest inside the host and allows the calculation of the respective association constant. [ABSTRACT FROM AUTHOR]

Highlights: [•] The so-called styrylflavylium compounds are promising alternatives to anthocyanins and related compounds. [•] They follow the same network of reactions of anthocyanins including hydration, tautomerization and cis–trans isomerization. [•] The absorption spectra of styrylflavyliums are red shifted in comparison with the flavylium analogues. [•] A switching photochromic system from yellow to green is obtained in the presence of CTAB micelles. [Copyright &y& Elsevier]

Abstract: The compounds 3′-butoxy-7-methoxyflavylium and 3′-butoxy-7-hydroxyflavylium were synthesized and the respective equilibrium and rate constants determined by two complementary techniques, pH jumps and flash photolysis. An experimental strategy based on these two techniques allowed calculation of all the equilibrium and rate constants of the system carried out for the first time in flavylium compounds lacking of the high cis–trans isomerization barrier. Irradiation of the trans-chalcone gives rise to the formation of the cis-chalcone still during the lifetime of the flash, which disappears through two parallel reactions: (i) one leading to the recovery of the trans-chalcone and the other, (ii) forming flavylium cation via hemiketal. This last reaction is globally dependent on pH and at less acidic pH the system reverts back to the trans-chalcone. The highest yield of colour production upon the flash takes place in the pH range 2–3.5. [Copyright &y& Elsevier]

The syntheses, thermodynamic and kinetic properties of a series of 2-styryl-1-benzopyrylium compounds are reported. This family of compounds was found to follow the same pH- and light-dependent network of chemical reactions previously described for flavylium (2-phenyl-1-benzopyrylim) compounds. However, 2-styryl-1-benzopyrylium compounds exhibit absorption spectra substantially red shifted when compared with flavylium analogues (up to 90nm). In particular, a photochromic system switching from yellow to light blue based on derivatives of natural anthocyanins is for the first time documented. [Copyright &y& Elsevier]