Activation of Anthraquinone's Electrophilicity by Light for a Dynamic C-O Bond.

Coupling of photoswitching with dynamic covalent chemistry enables control of the formation and cleavage of covalent bonds by light irradiation. peri-Aryloxyanthraquinones feature an exclusive ability to switch electrophilicity by interconversion between para- and ana-quinone isomers, which was used for the first time for the implementation of a dynamic C-O bond. Photogenerated ana-isomers undergo a concerted oxa-Michael addition of phenols to give hitherto unknown 4-hydroxy-10,10-diaryloxyanthracen-9-ones. These species were found to be in equilibrium with the corresponding ana-quinones, thus forming a dynamic covalent system of a new type. Withdrawal of the colored ana-quinones from the equilibria by visible light irradiation resulted in two para-quinones with "locked" aryloxy groups.

Revisiting Peri-Aryloxyquinones: From a Forgotten Photochromic System to a Promising Tool for Emerging Applications.

Emerging applications of photochromic compounds demand new molecular designs that can be inspired by some long-known yet currently forgotten classes of photoswitches. In the present review, we remind the community about Peri-AryloxyQuinones (PAQs) and their unique photoswitching behavior originally discovered more than 50 years ago. At the heart of this phenomenon is the light-induced migration of an aromatic moiety (arylotropy) in peri-aryloxy-substituted quinones resulting in ana-quinones. PAQs feature absorbance of both isomers in the visible spectral region, photochromism in the amorphous and crystalline state, and thermal stability of the photogenerated ana-isomer. Particularly noticeable is the high sensitivity of the ana-isomer towards nucleophiles in solution. In addition to the mechanism of molecular photochromism and the underlaying structure-switch relationships, we analyze potential applications and prospects of aryloxyquinones in optically switchable materials and devices. Due to their ability to efficiently photoswitch in the solid state, PAQs are indeed attractive candidates for such materials and devices, including electronics (optically controllable circuits, switches, transistors, memories, and displays), porous crystalline materials, crystalline actuators, photoactivated sensors, and many more. This review is intended to serve as a guide for researchers who wish to use photoswitchable PAQs in the development of new photocontrollable materials, devices, and processes.

Light-Induced Dyotropic Rearrangement of Diarylethenes: Scope, Mechanism, and Prospects.

Irreversible two-photon photorearrangement of 1,2-diarylethenes is a unique process providing access to complex 2a1 ,5a-dihydro-5,6-dithiaacenaphthylene (DDA) heterocyclic core. This reaction was serendipitously discovered during studies on photoswitchable diarylethenes and was initially considered as a highly undesired process. However, in recent years, it has been recognized as an efficient photochemical reaction, interesting by itself and as a promising synthetic method for the synthesis of challenging molecules. Herein, we discuss the state-of-the-art in studies on this notable process.

Multifunctional fluorescent diarylethene: time-resolved study of photochemistry.

A study of luminescence and photochromic properties of (E)-2,3-bis(2,5-dimethylthiophen-3-yl)-5-(4-(pyrrolidin-1-yl)benzylidene)cyclopent-2-en-1-one, which is a diarylethene with a push-pull system between carbonyl and dimethylamino groups, was performed using time-resolved methods. The intramolecular charge transfer (ICT) process as well as 6π-electrocyclization and E-/Z-isomerization contribute to the complex light-induced properties of this molecule. Formation of unexpected short-lived intermediates was detected in the time range from 100 fs to 100 µs. A model based on two processes (additional photocyclization and interconversion between conformers) was proposed to rationalize this result. The key intermediates existing in the picosecond time domain are so-called precursors, which are proposed for both parallel (p) and anti-parallel (ap) isomers of the open form. In general, fast light-induced processes for the fluorescent diarylcyclopentenones are much more complicated than for the parent cyclopentenone-based DAE.

Perceived Stigmatization among Dermatological Outpatients Compared with Controls: An Observational Multicentre Study in 17 European Countries.

Perceived stigmatization places a large psychosocial burden on patients with some skin conditions. Little is known about the experience of stigmatization across a wide range of skin diseases. This observational cross-sectional study aimed to quantify perceived stigmatization and identify its predictors among patients with a broad spectrum of skin diseases across 17 European countries. Self-report questionnaires assessing perceived stigmatization and its potential predictors were completed by 5,487 dermatology outpatients and 2,808 skin-healthy controls. Dermatological diagnosis, severity, and comorbidity were clinician-assessed. Patients experienced higher levels of perceived stigmatization than controls (p < 0.001, d = 0.26); patients with psoriasis, atopic dermatitis, alopecia, and bullous disorders were particularly affected. Multivariate regression analyses showed that perceived stigmatization was related to sociodemographic (lower age, male sex, being single), general health-related (higher body mass index, lower overall health), disease-related (higher clinician-assessed disease severity, presence of itch, longer disease duration), and psychological (greater distress, presence of suicidal ideation, greater body dysmorphic concerns, lower appearance satisfaction) variables. To conclude, perceived stigmatization is common in patients with skin diseases. Factors have been identified that will help clinicians and policymakers to target vulnerable patient groups, offer adequate patient management, and to ultimately develop evidence-based interventions.

White paper on psychodermatology in Europe: A position paper from the EADV Psychodermatology Task Force and the European Society for Dermatology and Psychiatry (ESDaP).

Psychodermatology is a subspecialty of dermatology that is of increasing interest to dermatologists and patients. The case for the provision of at least regional psychodermatology services across Europe is robust. Psychodermatology services have been shown to have better, quicker and more cost-efficient clinical outcomes for patients with psychodermatological conditions. Despite this, psychodermatology services are not uniformly available across Europe. In fact many countries have yet to establish dedicated psychodermatology services. In other countries psychodermatology services are in development. Even in countries where psychodermatolgy units have been established, the services are not available across the whole country. This is especially true for the provision of paediatric psychodermatology services. Also whilst most states across Europe are keen to develop psychodermatology services, the rate at which this development is being implemented is very slow. Our paper maps the current provision of psychodermatology services across Europe and indicates that there is still very much more work to be done in order to develop the comprehensive psychodermatology services across Europe, which are so crucial for our patients.

Body dysmorphia in common skin diseases: results of an observational, cross-sectional multicentre study among dermatological outpatients in 17 European countries.

BACKGROUND: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective, interventions. BDD symptoms are more prevalent in patients with dermatological conditions than in the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. OBJECTIVES: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. METHODS: This observational, cross-sectional, comparative multicentre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological outpatients at 22 clinics in 17 European countries, and 2808 healthy skin controls (66% female). BDD symptoms were assessed by the Dysmorphic Concern Questionnaire. Sociodemographic data and information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. The study was registered with number DRKS00012745. RESULTS: The average participation rate of invited dermatological patients was 82.4% across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than 11-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared with healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than sixfold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatization. CONCLUSIONS: Clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and management.

Photocyclization of Diarylethenes: The Effect of Electron and Proton Acceptors as Additives.

The effect of electron and proton acceptors on the photocyclization of diarylethenes has been studied. Without any additives, the deprotonation reaction is predominant, although other processes, including the sigmatropic shift, are not excluded. A deuterium exchange experiment has shown that a strong base (DABCO) facilitates the deprotonation reaction, thereby limiting the sigmatropic shift. In the presence of an oxidizing agent or additional sources of radicals (O2, I2, TEMPO), the processes of deprotonation and rearrangement (H-shift) are practically not observed, and the reaction proceeds along a radical pathway with the formation of phenanthrene or its heterocyclic analogue.

Azulene as an ingredient for visible-light- and stimuli-responsive photoswitches.

The azulene molecule features a unique combination of optical, luminescence, and stimuli-responsive properties. This makes the azulene motif a promising functional group to be introduced in photoswitches. Recent challenges in the field of photochromic compounds require the development of new approaches to molecules that are switched by visible light (400-760 nm), are proton responsive and have advanced luminescent properties. Merging azulene with photoswitches opens prospects for fulfilling these requirements. Herein, we highlight recent results on the application of this hydrocarbon motif in various photochromic systems, such as stilbenes, diarylethenes, and azobenzenes.

Photocontrollable Modulation of Frontier Molecular Orbital Energy Levels of Cyclopentenone-Based Diarylethenes.

Photoswitchable diarylethenes provide a unique opportunity to optically modulate frontier molecular orbital energy levels, thereby opening an avenue for the design of electronic devices such as photocontrollable organic field-effect transistors (OFETs). In the present work, the absolute position of the frontier orbital levels of nonsymmetrical diarylethenes based on a cyclopentenone bridge has been studied using cyclic voltammetry and density functional theory (DFT) calculations. It has been shown that varying heteroaromatic substituents make it possible to change the absolute positions of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of both diarylethene photoisomers. The data obtained are used to refine the operation mechanism of the previously developed OFET devices, employing the cyclopentenone-derived diarylethenes at the dielectric/semiconductor interface.

Chronic Nodular Prurigo: A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

Post-Modification of the Ethene Bridge in the Rational Design of Photochromic Diarylethenes.

Fine-tuning of the molecular structure of organic bistable compounds to improve their photochromic performance or to introduce additional functions remains an important issue in the development of photoresponsive materials. Diarylethenes bearing heterocyclic moieties belong to the most intensively studied class of organic photochromes due to their excellent photochemical properties. A huge number of diarylethenes have been synthesized so far. Analysis of the literature data shows that there are very worthy examples of diarylethenes developed by the Irie and Feringa groups, which can be the common starting material for a number of diarylethenes functionalized in hetaryl moieties. We refer to these structures as photochromic diarylethene precursors. These diarylethenes have proved to be very useful in the construction of functional molecules with desired properties. On the other hand, in our groups, we have elaborated on diarylethene precursors with modifiable ethene bridges. In this review, we have collected examples of such structures and their chemical modifications, leading to the improvement or fine-tuning of photochromic switching.

Switching the Mallory Reaction to Synthesis of Naphthalenes, Benzannulated Heterocycles, and Their Derivatives.

This review analyzes the new life of a long-known reaction, the photocyclization of diarylethenes, which became a classical tool for the synthesis of phenanthrenes and their heterocyclic analogues (Mallory reaction). It has been shown in recent years that certain diarylethenes undergo photorearrangement to naphthalenes, benzannulated heterocycles, or related products with bicyclic unit. Herein, I analyze how the Mallory reaction path can be altered to obtain bicyclic rather than tricyclic products. The mechanistic aspects and scope of the reaction are discussed.

Photorearrangement of dihetarylethenes as a tool for the benzannulation of heterocycles.

A general strategy for the preparative benzannulation of aromatic heterocycles via photocyclization of 1,2-dihetarylethenes was proposed for the first time. The strategy includes two steps, namely, modular assembly of dihetarylethenes from widely available 3-hetarylacetic acids and 2-bromo-1-hetarylethanones, and subsequent preparative photorearrangement (using a UV lamp at 365 nm as the light source). This approach is efficient for the annulation of a wide range of heterocycles and provides C-, N-, O- or S-substituents in the benzoheterocycles obtained. The photochemical step is a metal-, acid-, and oxidant-free reaction, which requires non-inert conditions, and can be easily monitored by NMR spectroscopy. Applicability of the proposed strategy was tested in the synthesis of a wide range of substituted carbazoles and benzo[b]thiophenes as well as on a gram-scale benzannulation of 3-indoleacetic acid. Our study disclosed how to overcome two notable obstacles to the successful photorearrangement of dihetarylethenes: undesired reactions associated with photogenerated singlet oxygen, and the instability of desired products. The first problem was successfully solved by the addition of DABCO, while development of an in situ alkylation protocol to trap unstable photoproducts allowed us to overcome the second issue.

Occurrence, Chronicity and Intensity of Itch in a Clinical Consecutive Sample of Patients with Skin Diseases: A Multi-centre Study in 13 European Countries.

Itch is an unpleasant symptom, affecting many dermatological patients. Studies investigating the occurrence and intensity of itch in dermatological patients often focus on a single skin disease and omit a control group with healthy skin. The aim of this multi-centre study was to assess the occurrence, chronicity and intensity (visual analogue scale 0-10) of itch in patients with different skin diseases and healthy-skin controls. Out of 3,530 dermatological patients, 54.3% reported itch (mean ± standard deviation itch intensity 5.5 ± 2.5), while out of 1,094 healthy-skin controls 8% had itch (3.6 ± 2.3). Chronic itch was reported by 36.9% of the patients and 4.7% of the healthy-skin controls. Itch was most frequent (occurrence rates higher than 80%) in patients with unclassified pruritus, prurigo and related conditions, atopic dermatitis and hand eczema. However, many patients with psychodermatological conditions and naevi also reported itch (occurrence rates higher than 19%).

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes.

A new family of photochromic diarylethene-based ligands bearing a 2-(imidazol-2-yl)pyridine coordination unit has been developed. Four members of the new family have been synthesized. The photoactive ligands feature non-aromatic ethene bridges (cyclopentene, cyclopentenone, and cyclohexenone), as well as closely spaced photoactive and metal coordination sites aiming a strong impact of photocyclization on the electronic structure of the coordinated metal ion. The ligands with cyclopentenone and cyclohexenone bridges show good cycloreversion quantum yields of 0.20-0.32. The thermal stability of closed-ring isomers reveals half-lives of up to 20 days in solution at room temperature. The ligands were used to explore coordination chemistry with iron(II) targeting photoswitchable spin-crossover complexes. Unexpectedly, dinuclear and tetranuclear iron(II) complexes were obtained, which were thoroughly characterized by X-ray crystallography, magnetic measurements, and Mössbauer spectroscopy. The formation of multinuclear complexes is facilitated by two coordination sites of the diarylethene, acting as a bridging ligand. The bridging nature of the diarylethene in the complexes prevents photocyclization.

Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial.

BACKGROUND: Chronic pruritus is a multifactorial, challenging symptom of global relevance. OBJECTIVE: The European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) investigation aimed to analyze the severity and humanistic burden of chronic pruritus in patients suffering from inflammatory dermatoses across Europe. METHODS: Prospectively collected routine data on 552 patients (with atopic dermatitis, contact dermatitis, prurigo nodularis, psoriasis vulgaris, lichen planus, or mycosis fungoides [pruritus numeric rating scale score ≥3]) from 9 European centers (in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland, and Turkey) were analyzed by univariate and multivariate variance analyses of various itch characteristics and quality of life (as measured by the Dermatology Life Quality Index and the ItchyQoL). RESULTS: Duration, frequency, and intensity of pruritus (according to a numeric rating scale and visual analog scale) and related impairment of quality of life differed between European centers and dermatologic diagnoses (P < .05). The country in which the center was located had a greater impact on how patients evaluated pruritus intensity and quality of life than diagnosis did (P < .001). LIMITATIONS: One center per country was included. CONCLUSION: The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high. European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life.

Mechanistic Aspects of Photoinduced Rearrangement of 2,3-Diarylcyclopentenone Bearing Benzene and Oxazole Moieties.

Photoinduced rearrangement of diarylethenes to naphthalenes or isoelectronic benzoannulated heterocycles is a novel reaction in preparative organic photochemistry. Recently it was shown that unsymmetrical diarylethenes containing benzene and oxazole derivatives efficiently undergo this transformation leading to amide derivatives of naphthalene. Mechanistic study of skeletal rearrangement for a typical representative of these compounds, namely 3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-phenylcyclopent-2-en-1-one, was performed by stationary and laser flash photolysis as well as density functional theory (DFT) calculations. The mechanism of the rearrangement was found to comprise several thermal stages. Both singlet and triplet states of the initial compound can be transformed to the reaction product, which results in the dependence of the quantum yield vs concentration of dissolved oxygen. Three reactive intermediates were registered in the laser flash photolysis experiment; the predicted structures were in accordance with DFT calculations of the electronic absorption spectra. In addition to the previously proposed mechanism of skeletal rearrangement based on a sigmatropic shift of hydrogen, two new parallel pathways based on formation of a carbanion/carbocation were determined.

Longer Duration of Untreated Psychosis is Associated with Poorer Outcomes for Patients with Delusional Infestation.

We examined the association between the duration of untreated psychosis and outcome for patients with delusional infestation. This multi-centre international study included 211 consecutive patients. Illness severity was evaluated at first presentation and outcome was measured with the Clinical Global Impression scale (CGI) at baseline and follow-up. A regression analysis showed a clear clinical and statistically significant association between shorter duration of untreated psychosis and better outcome at follow-up. Patients with a duration of untreated psychosis of less than one year showed a CGI-S change from 5.37 to 2.07; those with a duration of untreated psychosis of 1-5 years a change from 5.48 to 2.59, and those with a duration of untreated psychosis of >5 years a change from 5.59 to 3.37. This difference of 1.1 CGI points between the groups resembles a clinically relevant difference in patient outcome. Our results suggest that longer duration of untreated psychosis in patients with delusional infestation is associated with significantly less favour-able clinical outcomes.