Multistate/multifunctional systems. A thermodynamic,kinetic, and photochemical investigation of the 4'-dimethylaminoflavylium compound

The 4'-dimethylaminoflavylium ion in aqueous solution undergoes an intricate network of chemical reactions controlled by pH and light excitation. It is shown that nine different forms are involved, including two species that are not present in previously investigated compounds of the flavylium family. The thermodynamic and kinetic constants of the equilibria and interconversion processes have been obtained by pH jump (included stopped-flow) experiments. The photochromic properties exhibited by the trans/cis chalcone forms have been investigated. The peculiar aspect of 4'-dimethylaminoflavylium, as compared to previously investigated compounds of the same family, is a close to planarity structure, as demonstrated by the X-ray analysis on the parent 4'-aminoflavylium compound (2.3 degrees torsion angle between the benzopyrylium and benzene ring). The results obtained show that the flavylium cation is strongly stabilized by the electron-donor character of the dimethylamino substituent on the benzene ring. The donor-acceptor interaction makes both the protonation of the amino group and the hydration of the flavylium cation difficult, with consequences on the tautomerization and cis/trans isomerization reactions. The multistate/multifunctional properties of 4'-dimethylaminoflavylium have been discussed in the frame of write-lock-read-unlock-erase cycles.     

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.     

Multistate properties of 7-(N,N-diethylamino)-4'-hydroxyflavylium. An example of an unidirectional reaction cycle driven by pH

The synthetic flavylium salt 7-(N,N-diethylamino)-4'-hydroxyflavylium tetrafluoroborate gives rise in aqueous solution to a complex network of chemical reactions driven by pH. The system was studied by 1H NMR, single crystal X-ray diffraction, steady state and transient UV-Vis spectrophotometry as well as stopped flow. The crystal structure shows a high degree of coplanarity between the pyrylium system and the phenyl group in position 2. Thermodynamic and kinetic constants for the pH dependent network of chemical reactions were obtained. The introduction of an amino group in position 7 allows formation of protonated species leading, in particular, to a tautomeric form of the protonated cis-chalcone, H+, whose absorption spectra is rather red shifted, in comparison with the correspondent protonated trans-chalcone, H+. The H+ species can be rapidly converted into the flavylium cation through a first order process with lifetime of 0.2 s at pH = 2.35. This new reaction channel confers this compound a peculiar behaviour in acidic media, allowing to define an unidirectional pH driven reaction cycle.     

Solvent effects on the thermal and photochemical reactions of 4'-iodo-8-methoxyflavylium and their consequences on the coloring phenomena caused by anthocyanins in plants

The chemistry and photochemistry of the compound 4'-iodo-8-methoxyflavylium tetrafluoroborate was studied in solvent mixtures of water and ethanol. The trans-chalcone form (Ct) is always the most stable species at equilibrium. In particular, for the first time, Ct and not the flavylium cation is reported as the most stable species in mixtures containing water at pH 1.0. The rate of Ct formation as a function of the water content exhibits a bell-shaped dependence, showing a maximum at approximately 50 % water. These trends are explained by a slower cis-trans isomerization in ethanol relative to that in water due to the expected stabilization in polar solvents of the zwitterionic intermediate; on the other hand, the decrease in the concentration of cis-chalcone (Cc) in the pseudoequilibrium with increasing water content, gives rise to a decrease in the rate of Ct formation (k(obs)=k(real)[Cc]). The hydration reaction was found to be much more efficient when water is present in low concentrations. This result has important consequences for the interpretation of the coloring phenomena caused by anthocyanins in plants, as well as for applications of flavylium compounds in the field of optical memories.     

Multistate/multifunctional behaviour of 4'-hydroxy-6-nitroflavylium: a write-lock/read/unlock/enable-erase/erase cycle driven by light and pH stimulation

We have investigated the network of reactions observed for the photochromic 4'-hydroxy-6-nitroflavylium compound in aqueous solutions upon pH changes (including pH jump and stopped flow experiments) and light excitation. The changes observed in the NMR and UV/Vis spectra allowed identification of ten different forms in which this compound can be transformed depending on the experimental conditions. Equilibrium and kinetic constants have been determined. Compared with other members of the flavylium family, 4'-hydroxy-6-nitroflavylium is characterized by a large cis-->trans isomerization barrier, and a very efficient hydration reaction. These peculiar features allow writing, reading, storing and erasing photonic information on 4'-hydroxy-6-nitroflavylium by a novel cyclic process that involves the following steps: write-lock/read/unlock/enable-erase/erase.     

Complete resolution of the reaction Rates of flavylium Networks. The role played by 2-phenyl-2H-chromen-4-ol and the hydroxyl attack to the quinoidal Base

Complete analytical resolution of the network of chemical reactions involving the flavylium compounds was achieved by means of the Laplace transform, general partial fraction theorem and Vieta’s formulae. The kinetic model includes basic and acid catalysis of the hydration and tautomerization reactions. The formation of phenyl-2H-chromen-4-ol (B ₄ ) and the role it plays in the kinetics in the case of compounds lacking of the hydroxyl substituents was also accounted for. In all cases four kinetic steps could be individualized and the pH dependent mole fraction distribution of the several species monitored as a function of time, the last one leading to the equilibrium. It is worth of note the role of B ₄ in the network, which like the quinoidal base is a kinetic product that retards the formation of Ct. The evolution of B ₄ is also dependent on the existence or not of the cis-trans isomerisation barrier. Application of the model to the data of flavylium networks previously reported in literature, predicts with great accuracy the respective behavior.     

Flavylium Network of Chemical Reactions in Confined Media: Modulation of 3′,4′,7‐Trihydroxyflavilium Reactions by Host–Guest Interactions with Cucurbit[7]uril

In moderately acidic aqueous solutions, flavylium compounds undergo a pH‐, and in some cases, light‐dependent array of reversible chemical reactions. This network can be described as a single acid–base reaction involving a flavylium cation (acidic form) and a mixture of basic forms (quinoidal base, hemiketal and cis and trans chalcones). The apparent pK′_a of the system and the relative mole fractions of the basic forms can be modulated by the interaction with cucurbit[7]uril. The system is studied by using ¹H NMR spectroscopy, UV/Vis spectroscopy, flash photolysis, and steady‐state irradiation. Of all the network species, the flavylium cation possesses the highest affinity for cucurbit[7]uril. The rate of interconversion between flavylium cation and the basic species (where trans‐chalcone is dominant) is approximately nine times lower inside the cucurbit[7]uril.     

Living polymerization of aryl substituted acetylenes by MoCl5 and WCl6 based initiators: The ortho phenyl substituent effect

The polymerization of phenylacetylene initiated by MoCl₅ and WCl₆ based initiators was monitored directly in the NMR sample tube and demonstrated the presence of backbiting and intramolecular cyclization reactions. It was shown that the ratio of cis to trans structural units obtained by isomerization prior to double bond formation dictates the degree of backbiting and intramolecular cyclization reactions. This cis–trans ratio determines the length of cis–transoidal sequences present in the polymer backbone which are available for both backbiting and intrachain cyclization reactions. The cyclic trimers obtained in the metathesis polymerization of phenylacetylene are formed only through the cis–cisoidal-induced backbiting and/or intramolecular reactions. The o-trimethylsilylphenylacetylene follows a living mechanism of polymerization. This is due to the fact that the size of the ortho substituent suppresses the cis–transoidal to cis–cisoidal isomerization reactions and therefore eliminates the backbiting reactions. The steric hindrance provided by the size of the ortho substituent also eliminates interchain and intrachain reactions.     

Probing highly efficient photoisomerization of a bridged azobenzene by a combination of CASPT2//CASSCF calculation with semiclassical dynamics simulation

Mechanism of phototriggered isomerization of azobenzene and its derivatives is of broad interest. In this paper, the S(0) and S(1) potential energy surfaces of the ethylene-bridged azobenzene (1) that was recently reported to have highly efficient photoisomerization were determined by ab initio electronic structure calculations at different levels and further investigated by a semiclassical dynamics simulation. Unlike azobenzene, the cis isomer of 1 was found to be more stable than the trans isomer, consistent with the experimental observation. The thermal isomerization between cis and trans isomers proceeds via an inversion mechanism with a high barrier. Interestingly, only one minimum-energy conical intersection was determined between the S(0) and S(1) states (CI) for both cis → trans and trans → cis photoisomerization processes and confirmed to act as the S(1) → S(0) decay funnel. The S(1) state lifetime is ～30 fs for the trans isomer, while that for the cis isomer is much longer, due to a redistribution of the initial excitation energies. The S(1) relaxation dynamics investigated here provides a good account for the higher efficiency observed experimentally for the trans → cis photoisomerization than the reverse process. Once the system decays to the S(0) state via CI, formation of the trans product occurs as the downhill motion on the S(0) surface, while formation of the cis isomer needs to overcome small barriers on the pathways of the azo-moiety isomerization and rotation of the phenyl ring. These features support the larger experimental quantum yield for the cis → trans photoisomerization than the trans → cis process.     

Photochromic soft materials: flavylium compounds incorporated into pluronic F-127 hydrogel matrixes

The performance of flavylium-based photochromic systems is increased by their incorporation into Pluronic F-127 matrixes, which switch from polymeric solutions to micelles to gels with changes in temperature depending on copolymer concentration. Two flavylium compounds, 7,4'-dihydroxyflavylium and 7-(N,N-diethylamino)-4-hydroxyflavylium, both exhibiting a small thermal cis-trans isomerization barrier in water were investigated. In the first system the flavylium in the gel photoswitches from the colorless trans-chalcone (Ct) species to the yellow flavylium cation (AH+) with quantum yield Phi=0.04 (25 degrees C) at pH 2.2 or to the orange quinoidal base (A) with quantum yield Phi=0.015 (25 degrees C) at pH 5.2. The photoproducts revert back to their initial form by a thermal process characterized by first-order kinetics; the rate constants exhibit a bell shape variation with pH, with a maximum at pH 4.3 (lifetime 4.2 min). The second system, 7-(N,N-diethylamino)-4-hydroxyflavylium, does not exhibit photochemistry in water but, when incorporated into the Pluronic F-127 gel, switches from yellow to red with a quantum yield of Phi=0.01 at pH 4.9. The respective thermal back reaction takes place with a lifetime of 66.7 min1. The flavylium network of chemical reactions is a good sensor for the detection of not only the critical micelle temperature but also the gelation temperature of Pluronic and like solutions and, in some instances, the exposure to UV and visible radiation.     

Hydroxypyridinechromene and Pyridinechalcone: Two Coupled Photochromic Systems

Substitution of the phenyl group in 2‐hydroxychalcones by a 4‐pyridine unit dramatically changes the network of chemical reactions of this compound: trans‐chalcone‐type ( Ct ), cis‐chalcone‐type ( Cc ), and a hemiketal (hydroxy‐4‐pyridinechromene) ( B ) and their protonated forms are formed, but the presence of a flavylium‐type cation could not be detected even at very acidic pH values. Moreover, whereas in 2‐phenyl‐2‐benzopyrylium compounds B and Cc are generally elusive species whose kinetic processes in aqueous solutions occur on the sub‐second timescale, in the present compound these species equilibrate on a timescale four orders of magnitude lower. Complete characterization of the equilibrium and kinetics of the reaction network could thus be achieved by ¹H NMR spectroscopy and UV/Vis spectrophotometry. The network of chemical reactions exhibits cis–trans photoisomerization, as well as photochromism between the hemiketal and the chalcone‐type species. The irradiation of Ct in MeOH/H₂O (1:1) at 365 nm produces B almost quantitatively through two consecutive photochemical reactions: Ct → Cc photoisomerization followed by Cc → B photo ring closure with a global quantum yield of 0.02. On the other hand, irradiation of B at 254 nm leads to a photostationary state composed by 80 % Ct and 20 % B , with a quantum yield of 0.21.     

Enol-to-keto tautomerism of peptide groups

Density functional based simulations, performed on polyglycine containing an enol peptide group [-C(OH)N-] which is a structural isomer of a keto form [-CONH-], show that in the enol-to-keto tautomeric reaction, the enol peptide group is less stable than the keto form, and that the enol-to-keto tautomerism is characterized by a cis/trans isomerization of the C-N peptide bond. The rate-limiting step in the cis/trans isomerization is a hydrogen migration from O to N atoms in the peptide group with a transition state consisting of a four-membered ring in the cis configuration. An analysis of the cis/trans isomerization pathway shows that the mechanisms for the cis/trans isomerization are essentially different between the enol and keto forms.     

Mechanistic study of trans⇆cis isomerization of the substituted azobenzene moiety bound on a liquid‐crystalline polymer

A mechanistic study of the trans?cis isomerization of the azobenzene moiety in a side‐chain liquid‐crystal polymer system was carried out with six liquid‐crystalline polymethacrylates in which different electron‐withdrawing substituents were attached to the para‐positions of the azobenzene chromophores. Compared to the non‐nitro‐substituted azo polymers, the nitro‐substituted azo polymers exhibited two quite different behaviors: an extraordinarily high reaction rate of the thermal cis–trans isomerization and an unexpected composition of cis–trans isomers obtained from the photochemical trans–cis isomerization process. A potential energy profile for the isomerization process was established on basis of the structures of the proposed transition states and was employed to elucidate the reaction mechanism. The results confirmed that the nitro‐substituted azo polymer system proceeded via a rotation mechanism in either direction of the trans?cis isomerization reaction, whereas the non‐nitro‐substituted species were more likely to follow an inversion mechanism. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2296–2307, 2001     

Photoswitchable dendritic hosts: a dendrimer with peripheral azobenzene groups

We have studied the adducts formed by eosin (E) with a fourth generation dendrimer (D) that comprises 30 tertiary amine units in the interior and 32 naphthyl and 32 trans azobenzene units in the periphery. We have found that: (i) the all trans dendrimer D(32t) can be converted by irradiation with 365 nm light (Phi=0.12) into species containing, as an average, 4 trans and 28 cis azobenzene units, D(4t28c), that at 313 K undergoes a D(4t28c) --> D(32t) thermal back reaction (k = 7.0 x 10(-5) s(-1)); (ii) D(32t) and D(4t28c) extract 8 and, respectively, 6 eosin molecules from water at pH 7, yielding the species D(32t) subset 8E and D(4t28c) subset 6E; (iii) eosin uptake is significantly faster for D(32t) than for D(4t28c); (iv) irradiation at 365 nm of the D(32t) subset 8E species at 298 K leads to the release of two eosin molecules with formation of a photostable D(15t17c) subset 6E species (Phi = 0.15) that is also obtained from the back thermal reaction of D(4t28c) subset6E at 313 K (k = 2.7 x 10(-5) s(-1)); (v) thermal release of E from D(32t) subset 6E is much faster than from D(4t28c) subset 6E; and (vi) excitation of E in the adducts sensitizes the cis --> trans (but not the trans --> cis) isomerization. The results obtained show that the isomerization of the 32 peripheral azobenzene units controls to some extent the hosting capacity of the dendrimer and, viceversa, eosin molecules hosted in the dendrimer affect the isomerization process of its azobenzene units.     

Kinetics of the cis,cis to trans,trans isomerization of 1,1,2,2,5,5,6,6-octamethyl-1,2,5,6-tetrasilacycloocta-3,7-diene

The kinetics of the ruthenium-promoted cis,cis to trans,trans isomerization of 1,1,2,2,5,5,6,6-octamethyl-1,2,5,6-tetrasilacycloocta-3,7-diene were investigated. Incubation of a ruthenium alkylidene complex, (Cy(3)P)RuCl(2)(==CHPh)Ru(p-cymene)Cl(2), in CD(2)Cl(2) for 5 days at 40 degrees C afforded a catalytically active ruthenium species that was shown to be responsible for promoting the isomerization. The isomerization was observed to proceed in two steps: (1) conversion of the starting cis,cis isomer to a proposed cis,trans intermediate and (2) subsequent conversion of the intermediate to the product trans,trans isomer. Kinetic studies demonstrated that the two steps are first-order with respect to the concentrations of the cis,cis isomer, the intermediate, and the ruthenium alkylidene complex. The data were further consistent with a mechanism involving bimolecular hydride addition-elimination during the two isomerization steps.     

ADVENTITIOUS INTERCONVERSION OF cis- AND trans-UROCANIC ACID BY LABORATORY LIGHT

Urocanic acid (UCA) is a chromophore in the stratum corneum. Ultraviolet radiation (ultraviolet B) has been shown to suppress mammalian cell-mediated immunity. The photoisomerization of trans -UCA to cis -UCA was proposed as the initiator of the suppression process. Cis -urocanic acid has been demonstrated to suppress immunity by a variety of experiments. Investigators should be aware that laboratory illumination may be capable of interconverting trans -UCA and cis -UCA during experimental manipulations. This possible inadvertent contamination of one isomer by the other may influence results. We demonstrated that fluorescent lamps, daylight, sunlight and incandescent lamps were able to bring about isomerization. Window glass and container materials of plastic and clear glass did not filter out effective wavelengths, but three commercial plastic diffusers on fluorescent fixtures prevented the isomerization. Because the molar extinction coefficient (ɛ) for cis -UCA is less than that of trans -UCA, we have exposed 0.1 m M trans -UCA to ambient light and monitored the change in absorbance. A method is given to calculate the percentage of trans and cis isomers from the absorbance at 277 nm when the initial purity and absorbance are known. Using this procedure, we validated the molar extinction coefficient of cis -UCA.     

MOLECULAR MECHANISMS IN VISUAL PIGMENT REGENERATION

The photochemical bleaching of vertebrate rhodopsin results in the cis to trans isomerization of the 11-cis-retinal protonated Schiff base. Hydrolysis of the Schiff base leads to the formation of opsin and all-trans-retinal. In order for vision to proceed, the enzymatic trans to cis isomerization of a retinoid must occur. Since retinoids exist as alcohols, aldehydes, or esters in the eye, there are potentially nine different routes for isomerization. Moreover, 11-cis-retinoids are approximately 4 kcal/mol higher in energy than their all-trans isomers. Thus, not only must the isomerization route be defined, but an energy source must be identified to power this process. It was discovered that the energy is provided for in a minimally two-step process involving membrane phospholipids as the energy source. First, all-trans-retinol (vitamin A) is esterified in the retinal pigment epithelium by lecithin retinol acyl transferase to produce an all-trans-retinyl ester. Second, this ester is directly transformed into 11-cis-retinol by an isomerohydrolase enzyme, in a process that couples the negative free energy of hydrolysis of the acyl ester to the formation of the strained 11-cis-retinoid.     

Oxidation-state and metal-ion dependent stereoisomerization in oxo molybdenum and tungsten complexes of a bulky alkoxy heteroscorpionate ligand

Monooxo Mo(V) complexes of a N2O heteroscorpionate ligand designated (L10O) are found to exist as isolable cis and trans isomers. We have been able to trap the kinetically labile cis isomer and follow its isomerization to the thermodynamically more stable trans form. We have also followed the kinetics of isomerization between the cis and trans isomers of the corresponding dioxo Mo(VI) and W(VI) species. Here the trans is the labile isomer that spontaneously converts to the thermodynamically more stable cis. It is observed that at 60 degrees C in DMSO the Mo(VI) complex isomerizes approximately 6.5 times faster than the Mo(V) and nearly 5 times faster than the corresponding W(VI) analogs. The temperature dependence to the kinetics of the Mo(V) and Mo(VI) isomerizations give activation parameters that are similar for both oxidation states and consistent with those previously observed in [(L1O)MoOCl2] suggesting a similar twist mechanism is operating in all cases. Thus there are oxidation state, metal ion and donor atom dependent differences in isomeric stability that could have significant implications for understanding the mechanisms of both enzymatic and nonenzymatic oxo atom transfer reactions catalyzed by complexes of Mo, W and Re.     

Direct calculation of interconversion barriers in dynamic chromatography and electrophoresis: Isomerization of captopril

Dynamic capillary electrophoresis (DCE) and direct calculation of the rate constants of isomerization has been applied to determine the cis-trans isomerization barriers of the angiotensin-converting enzyme inhibitor captopril. The separation of the rotational cis-trans isomeric drug has been performed in an aqueous 50 mM borate buffer at pH 9.3. Interconversion profiles featuring plateau formation, peak-broadening, and peak coalescence were observed. To determine the rate constants of the forward and backward reaction (k(cis-->trans) and k(trans-->cis)) of the isomerization process in dynamic capillary electrophoresis, a novel straightforward calculation method using the experimental parameters plateau height, h(plateau), peak width at half height w(h), the total migration times of the cis-trans isomers t(R) and the electroosmotic break-through time t(0) as well as the peak ratio of the cis-trans isomers is presented for the first time. From temperature dependent measurements the rate constants k(cis-->trans) and k(trans-->cis) and the kinetic activation parameters DeltaG( not equal), DeltaH( not equal), and DeltaS( not equal) of the cis-trans isomerization of captopril were obtained. From the activation parameters the isomerization barriers of captopril at 37 degrees C under basic conditions were calculated to be DeltaG( not equal) (cis-->trans) = 90.3 kJ.mol(-1)and DeltaG( not equal) (trans-->cis) = 90.0 kJ.mol(-1*).