Synthesis and Photovoltaic Performance of ß-Amino-Substituted Porphyrin Derivatives.

New ß-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63-74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (Voc) and short-circuit current density (Jsc) values.

Acenaphthylene-Based Chromophores for Dye-Sensitized Solar Cells: Synthesis, Spectroscopic Properties, and Theoretical Calculations.

A set of acenaphthylene dyes with arylethynyl π-bridges was tested for dye-sensitized solar cells (DSSCs). Crucial steps for the extension of the conjugated system from the acenaphylene core involved Sonogashira coupling reactions. Phenyl, thiophene, benzotriazole, and thieno-[3,2-b]thiophene moieties were employed to extend the conjugation of the π-bridges. The systems were characterized by cyclic voltammetry and by UV-vis absorption and emission. The spectroscopic characterization showed that the last three bridges resulted in red-shifted absorption and emission spectra relative to the parent phenyl-bridged compound, in accordance with TD-DFT calculations. The phenylethynyl derivative 6a achieved a conversion efficiency of 2.51% with Voc, Jsc, and FF values of 0.365 V, 13.32 mA/cm2, and 0.52, respectively. The efficiency of this compound improved to 3.15% with the addition of CDCA (10 mM), representing the best efficiency result in this study. The overall conversion efficiency of the other aryl derivatives 6b-d proved to be significantly inferior (14-40%) to that of 6a due to a significant decrease of Jsc.

Comparing the Chemistry of Malvidin-3-O-glucoside and Malvidin-3,5-O-diglucoside Networks: A Holistic Approach to the Acidic and Basic Paradigms with Implications in Biological Studies.

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 B42-, a kinetic product that decreases the overall equilibration rate, was observed only for the diglucoside.

Phototransduction in a supramolecular cascade: a mimic for essential features of the vision process.

The tailored design of a light-triggered supramolecular cascade results in an artificial machinery that assimilates the transduction of photons into chemical communication and the final release of a neurotransmitter. This is reminiscent of key steps in the natural vision process.

Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells: A selective strategy for targeting primary hyperoxaluria diseases.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8-24.5 %) and encapsulation efficiencies (31.9-40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 µM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 µM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.

Intermolecular Copigmentation of Malvidin-3-O-glucoside with Caffeine in Water: The Effect of the Copigment on the pH-Dependent Reversible and Irreversible Processes.

Intermolecular copigmentation of malvidin-3-O-glucoside with caffeine was studied using a holistic procedure that includes the extension to basic pH values. In moderately basic solutions (7.5 < pH < 9.5) and independently of the copigment presence, there is a pH region where degradation of the quinoidal base and anionic quinoidal bases is faster than hydration and OH- nucleophilic addition, preventing the system from reaching the equilibrium. Intermolecular copigmentation with caffeine reduces significantly the degradation rate of quinoidal bases. In a more basic medium, the equilibrium is reached and degradation occurs from the anionic chalcones. In this case, the addition of caffeine also reduces the degradation rate in the interval 10 < pH < 11.5.

Efforts for the Correct Comprehension of Deceitful and Ironic Communicative Intentions in Schizophrenia: A Functional Magnetic Resonance Imaging Study on the Role of the Left Middle Temporal Gyrus.

Deficits in social cognition and more specifically in communication have an important impact on the real-life functioning of people with schizophrenia (SZ). In particular, patients have severe problems in communicative-pragmatics, for example, in correctly inferring the speaker's communicative intention in everyday conversational interactions. This limit is associated with morphological and functional alteration of the left middle temporal gyrus (L-MTG), a cerebral area involved in various communicative processes, in particular in the distinction of ironic communicative intention from sincere and deceitful ones. We performed an fMRI study on 20 patients with SZ and 20 matched healthy controls (HCs) while performing a pragmatic task testing the comprehension of sincere, deceitful, and ironic communicative intentions. We considered the L-MTG as the region of interest. SZ patients showed difficulties in the correct comprehension of all types of communicative intentions and, when correctly answering to the task, they exhibited a higher activation of the L-MTG, as compared to HC, under all experimental conditions. This greater involvement of the L-MTG in the group of patients could depend on different factors, such as the increasing inferential effort required in correctly understanding the speaker's communicative intentions, and the higher integrative semantic processes involved in sentence processing. Future studies with a larger sample size and functional connectivity analysis are needed to study deeper the specific role of the L-MTG in pragmatic processes in SZ, also in relation to other brain areas.

Modulating the thermodynamics, kinetics and photochemistry of 7-diethylamino-4'-dimethylaminoflavylium in water/ethanol, SDS and CTAB micelles.

The thermodynamics and kinetics of compound 7-diethylamino-4'-dimethylaminoflavylium were studied in water : ethanol (1 : 1) and water in the presence of SDS and CTAB micelles. The blue flavylium cation is in equilibrium with the pink protonated flavylium cation defined by pKAH2+/AH+ and the yellow trans-chalcone, defined by pKAH+/Ct. The difference between these two pKs gives the pH domain of the flavylium cation, ΔpK = 1.95 in CTAB, ΔpK = 5.6 in water/ethanol (1 : 1) and ΔpK = 8.5 in SDS micelles. On the other hand, the pH domain of the trans-chalcone is limited by pKAH+/Ct and pKCt/Ct-. It is lower in SDS micelles ΔpK = 2.7, increases in ethanol/water (1 : 1) ΔpK = 5.1 and is maximum in CTAB micelles, ΔpK = 6.8. All these effects can be explained by the electric charge present at the micellar surface. Relative energy level diagrams that allow for the explanation of the driving forces for any pH stimuli or light absorption were constructed from the calculated equilibrium constants. Irradiation of the trans-chalcone at 466 nm leads to the formation of the flavylium cation. In water : ethanol (1 : 1), the photochemistry is residual with Φ < 0.00002, while in SDS micelles at pH = 7 light increases the rate of the spontaneous conversion of trans-chalcone to the flavylium cation, with quantum yield Φ = 0.002; photochromism from trans-chalcone to give the flavylium cation with the same quantum yield is also observed in CTAB micelles.

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.

Light- and pH-regulated Water-soluble Pseudorotaxanes Comprising a Cucurbit[7]uril and a Flavylium-based Axle.

A linear double pyridinium-terminated thread comprising a central chalcone moiety is shown to provide two independent binding sites with similar affinity for cucurbit[7]uril (CB7) macrocycles in water as judged from NMR, UV-Visible and fluorescence spectroscopies. Association results in [2] and [3]pseudorotaxanes, which are both pH and photosensitive. Switching from the neutral chalcone to the cationic flavylium form upon irradiation at 365 nm under acidic conditions provided an enhanced CB7 association (K1:1 increases from 1.2×105  M-1 to 1.5×108  M-1 ), limiting spontaneous on-thread cucurbituril shuttling. This co-conformational change in the [2]pseudorotaxane is reversible in the dark with kobs =4.1×10-4  s-1 . Threading the flavylium moiety into CB7 leads to a dramatic increase in the fluorescence quantum yield, from 0.29 in the free axle to 0.97 in the [2]pseudorotaxane and 1.0 in the [3]pseudorotaxane.

A Transcriptomic Approach to the Metabolism of Tetrapyrrolic Photosensitizers in a Marine Annelid.

The past decade has seen growing interest in marine natural pigments for biotechnological applications. One of the most abundant classes of biological pigments is the tetrapyrroles, which are prized targets due their photodynamic properties; porphyrins are the best known examples of this group. Many animal porphyrinoids and other tetrapyrroles are produced through heme metabolic pathways, the best known of which are the bile pigments biliverdin and bilirubin. Eulalia is a marine Polychaeta characterized by its bright green coloration resulting from a remarkably wide range of greenish and yellowish tetrapyrroles, some of which have promising photodynamic properties. The present study combined metabolomics based on HPLC-DAD with RNA-seq transcriptomics to investigate the molecular pathways of porphyrinoid metabolism by comparing the worm's proboscis and epidermis, which display distinct pigmentation patterns. The results showed that pigments are endogenous and seemingly heme-derived. The worm possesses homologs in both organs for genes encoding enzymes involved in heme metabolism such as ALAD, FECH, UROS, and PPOX. However, the findings also indicate that variants of the canonical enzymes of the heme biosynthesis pathway can be species- and organ-specific. These differences between molecular networks contribute to explain not only the differential pigmentation patterns between organs, but also the worm's variety of novel endogenous tetrapyrrolic compounds.

Children with hearing impairment and early cochlear implant: A pragmatic assessment.

Extensive research has demonstrated the benefits of cochlear implants (CI) in contributing to improve the linguistic skills of children with hearing impairment; however, few studies have focused on the development of pragmatic ability and its relationship with age of implantation. Pragmatics is the ability to use language in different contexts and its development has crucial implications, e.g., social inclusion and professional attainments. In this study, we conducted a comprehensive assessment of pragmatic ability using the Language Pragmatic Abilities (APL Medea), a battery composed by five different tasks: Comprehension of Metaphors, Implicit meaning, Comics, Situations and Colors Game (a perspective taking task). Eighteen children with early CI, belonging to 3 different age groups (6; 11-7; 11, 8; 0-8; 11 and 9; 0-9; 11 years-old), and twenty-four children with typical development (Control Group) participated to the study. We also investigated how the precocity of CI, i.e., age of first implantation, may affect the pragmatic development. Globally, children with CI obtained lower scores in the APL Medea battery than typically hearing children. However, focusing on the Medea tasks separately, children with CIs differed from their hearing peers only in Comics and Colors Game tasks. Finally, age of implantation was a moderate but significant predictor of pragmatic performance.

New 3-Ethynylaryl Coumarin-Based Dyes for DSSC Applications: Synthesis, Spectroscopic Properties, and Theoretical Calculations.

A set of 3-ethynylaryl coumarin dyes with mono, bithiophenes and the fused variant, thieno [3,2-b] thiophene, as well as an alkylated benzotriazole unit were prepared and tested for dye-sensitized solar cells (DSSCs). For comparison purposes, the variation of the substitution pattern at the coumarin unit was analyzed with the natural product 6,7-dihydroxycoumarin (Esculetin) as well as 5,7-dihydroxycomarin in the case of the bithiophene dye. Crucial steps for extension of the conjugated system involved Sonogashira reaction yielding highly fluorescent molecules. Spectroscopic characterization showed that the extension of conjugation via the alkynyl bridge resulted in a strong red-shift of absorption and emission spectra (in solution) of approximately 73-79 nm and 52-89 nm, respectively, relative to 6,7-dimethoxy-4-methylcoumarin (λabs = 341 nm and λem = 410 nm). Theoretical density functional theory (DFT) calculations show that the Lowest Unoccupied Molecular Orbital (LUMO) is mostly centered in the cyanoacrylic anchor unit, corroborating the high intramolecular charge transfer (ICT) character of the electronic transition. Photovoltaic performance evaluation reveals that the thieno [3,2-b] thiophene unit present in dye 8 leads to the best sensitizer of the set, with a conversion efficiency (η = 2.00%), best VOC (367 mV) and second best Jsc (9.28 mA·cm-2), surpassed only by dye 9b (Jsc = 10.19 mA·cm-2). This high photocurrent value can be attributed to increased donor ability of the 5,7-dimethoxy unit when compared to the 6,7 equivalent (9b).

Photoresponsive Binding Dynamics in High-Affinity Cucurbit[8]uril-Dithienylethene Host-Guest Complexes.

The use of external stimuli to control the binding kinetics in supramolecular systems is of critical importance for the development of advanced molecular machines and devices. In this work, a study focused on the kinetics of a water-soluble host-guest system based on cucurbit[8]uril and two dithienylethene (DTE) photoswitches is reported. It is shown that for the DTE guest comprising two anionic sulfonate side arms appended to pyridinium moieties, the formation/dissociation of the pseudorotaxane structures is slowed down by more than 100000-fold with respect to its bipyridinium analogue. The decrease in ingression rate leads to the emergence of a competitive metastable product with the open DTE isomer that has an important influence in the overall binding kinetics. Moreover, the host-guest dissociation kinetics is demonstrated to be approximately 100-fold slower for the closed DTE isomer (t1/2 =107 h vs. t1/2 =1.2 h for the open isomer) allowing control over the dissociation rate with light.

Light-Mediated Toxicity of Porphyrin-Like Pigments from a Marine Polychaeta.

Porphyrins and derivatives form one of the most abundant classes of biochromes. They result from the breakdown of heme and have crucial physiological functions. Bilins are well-known representatives of this group that, besides significant antioxidant and anti-mutagenic properties, are also photosensitizers for photodynamic therapies. Recently, we demonstrated that the Polychaeta Eulalia viridis, common in the Portuguese rocky intertidal, holds a high variety of novel greenish and yellowish porphyrinoid pigments, stored as granules in the chromocytes of several organs. On the follow-up of this study, we chemically characterized pigment extracts from the worm's skin and proboscis using HPLC and evaluated their light and dark toxicity in vivo and ex vivo using Daphnia and mussel gill tissue as models, respectively. The findings showed that the skin and proboscis have distinct patterns of hydrophilic or even amphiphilic porphyrinoids, with some substances in common. The combination of the two bioassays demonstrated that the extracts from the skin exert higher dark toxicity, whereas those from the proboscis rapidly exert light toxicity, then becoming exhausted. One particular yellow pigment that is highly abundant in the proboscis shows highly promising properties as a natural photosensitizer, revealing that porphyrinoids from marine invertebrates are important sources of these high-prized bioproducts.

Chemical evolution of the colour systems generated by riccionidin A, 3-deoxyanthocyanidins and anthocyanins.

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.

A Photoelectrochemical Study of Bioinspired 2-Styryl-1-Benzopyrylium Cations on TiO2 Nanoparticle Layer for Application in Dye-Sensitized Solar Cells.

In the present work, five 2-styryl-1-benzopyrylium salts and their relative self-assembly processes towards TiO2 nanocrystalline layers were evaluated as photosensitizers in dye-sensitized solar cells (DSSCs). Integration of these 2-styryl-1-benzopyrylium salts with the semiconductor allow for the performance of highly specific functions suitable for smart applications in material science. Spectroscopic and photoelectrochemical measurements conducted on these five bio-inspired dyes, in solution and upon adsorption onto titanium dioxide films, allowed detailed discussion of the anchoring ability of the different donor groups decorating the 2-styryl-1-benzopyrylium core and have demonstrated their ability as photosensitizers. Our results suggest that the introduction of a dimethylamino group in position 4' of the 2-styryl-1-benzopyrylium skeleton can alter the conjugation of the molecule leading to larger absorption in the visible region and a stronger electron injection of the dye into the conduction band of TiO2. Moreover, our experimental data have been supported by theoretical calculations with the aim to study the energy of the excited states of the five compounds. In this specific case, the simulations reported contributed to better describe the properties of the compounds used and to help create the necessary basis for the design of new and targeted bio-inspired molecules.

The complexity of porphyrin-like pigments in a marine annelid sheds new light on haem metabolism in aquatic invertebrates.

True green pigments in the animal kingdom are scarce and are almost invariably porphyrinoids. Endogenous porphyrins resulting from the breakdown of haem are usually known as "bile pigments". The pigmentation of intertidal Polychaeta has long gained attention due to its variety and vivid patterning that often seems incompatible with camouflage, as it occurs with Eulalia viridis, one of the few truly green Polychaeta. The present study combined UV and bright-field microscopy with HPLC to address the presence and distribution of pigments in several organs. The results showed two major types of porphyrin-like pigments, yellowish and greenish in colour, that are chiefly stored as intraplasmatic granules. Whereas the proboscis holds yellow pigments, the skin harbours both types in highly specialised cells. In their turn, oocytes and intestine have mostly green pigments. Despite some inter-individual variation, the pigments tend to be stable after prolonged storage at -20 °C, which has important implications for future studies. The results show that, in a foraging predator of the intertidal where melanins are circumscribed to lining the nervous system, porphyrinoid pigments have a key role in protection against UV light, in sensing and even as chemical defence against foulants and predators, which represents a remarkable adaptive feature.

Ground and excited state properties of furanoflavylium derivatives.

The comparison of the ground-state reactivity of anthocyanins and aurone model compounds (i.e. with and without the furano bridge) has shown that the kinetic paradigm does not depend on the bridge but only on the hydroxyl substituent pattern, independently of the presence of the bridge: (i) bell shaped kinetics for those with two hydroxyl substituents in position 4' and 7, and (ii) four distinct kinetic steps for the mono substituted compounds with a hydroxyl in position 4'. The excited state proton transfer (ESPT) properties of these compounds were also investigated using steady-state and time-resolved spectroscopic techniques. It was found that the ESPT efficiency is significantly higher for the bridged compounds. Interestingly, pH-dependent steady-state fluorescence emission experiments show that in 4',7-dihydroxyfuranoflavylium the hydroxyl group in position 7 is the more acidic one in the excited state, while 1H NMR titration curves indicate a higher acidity constant in the ground state for the proton at the hydroxyl group in position 4'. Differently, the fluorescence emission spectrum of the quinoidal base deprotonated at position 7 is only observed upon excitation of the flavylium cation while the one from the base deprotonated at 4' is observed upon direct excitation.

pH-Dependent Multistate System Generated by a Synthetic Furanoflavylium Compound: An Ancestor of the Anthocyanin Multistate of Chemical Species.

The multistate of chemical species generated by 4'-hydroxy-3,2'-furanoflavylium is similar to that of anthocyanins and related compounds. This furanoflavylium multistate system was fully characterized by UV-visible and NMR spectroscopy, allowing determination of the respective equilibrium and rate constants. In contrast to the multistate generated by flavylium cations derived from anthocyanins and related compounds, the furanoflavylium multistate is characterized by much slower hydration and tautomerization (pyran ring opening-closing). In addition, the cis-trans isomerization of the chalcones of this system (2'-hydroxyaurones) is extremely slow when compared with anthocyanins. The observed similar order of magnitude for tautomerization and isomerization rate constants leads to peculiar kinetics from the flavylium cation (pH = 1) to the stable trans-chalcone (higher pH values). The hemiketal appears and disappears during the first stages of the kinetics, which gives the intermediate cis-chalcone (pseudo-equilibrium). This last species disappears in a much slower process, as fully characterized by 1H NMR, to give the final trans-chalcone.