Psychometric properties of the health literacy instrument in Brazil (HLS-EU-BR47).

BACKGROUND: Health literacy (HL) is a key component of health promotion and sustainability and contributes to well-being. Despite its global relevance, HL is an under-researched topic in South America but is now debuting its exploration in Brazil. To leverage its benefits for South America, the mere translation of validated tools into Portuguese is insufficient. Rather, it is necessary to examine their validity. This study aims to assess the psychometric properties of the European Health Literacy Questionnaire (HLS-EU-BR47) using the Item Response Theory (IRT) in a population-based sample of adults in Brazil. METHODS: A cross-sectional online study was conducted across Brazil and included 1028 participants aged 18 years and above (80% women). Cronbach's alpha, McDonald's omega, factor analysis, graded responses model, Item Characteristic Curve, HL levels based on this, HL standard calculation, IRT, and regular score correlation were computed. RESULTS: The instrument exhibit high reliability (Cronbach's alpha 0.95). Factor analysis yielded one factor. IRT was appropriate for data analysis because it allowed quality evaluation of items and constructed a scale to quantify HL. The 47 items and latent features of respondents in the same unit of measurement are positioned in the construction of the HLS-EU-BR47 instrument. The percentages of individuals at each HL level, calculated using IRT, were found to be comparable to those obtained through the standard computation, e.g., 3.2% of people reported very low HL versus 10.8% inadequate HL, 56.2% reported low HL versus 39.5% problematic HL, 31.1% had moderate HL versus 30.1% sufficient HL, and 9.5% had high HL versus 19.7% with excellent HL. The mean HL scores were comparable between women and men (33.9 vs. 33.7, P = 0.36). CONCLUSION: This study provides new evidence of the validity of a widely used HL instrument for the population of South America (in this case, Brazil). This tool can be utilized by citizens, health professionals, and regional/national policymakers to inform the development of initiatives to assess and improve the HL of individuals, groups, and communities. Further studies are needed to confirm and extend the findings and to explore the influence of local cultures and practices in the vast Brazilian territory on HL.

How to Stabilize Large Soluble (Hetero-)Acenes.

The higher acenes and azaacenes (>(aza)heptacenes) are fascinating, yet elusive materials. Their reactivity and sensitivity increases concomitantly with their size. In recent years, confinement techniques, that is isolation of acenes in matrices and on surfaces, has surpassed solution-based chemistry with respect to accessing the larger (hetero)acenes at the price of the accessibility of no more than a couple thousands of molecules. Isolating acenes in bulk quantities and in processable form is vital for applications in organic electronics as well as from a viewpoint from basic research. In this Perspective, we will discuss after a short historical outline their degradation pathways, and then will selectively highlight recent efforts in stabilizing soluble (aza)acenes.

Paper and nylon based optical tongues with poly(p-phenyleneethynylene)-fluorophores efficiently discriminate nitroarene-based explosives and pollutants.

Discrimination of nitroarenes with hydrophobic dyes in a polar (H2O) environment is difficult but possible via a lab-on-chip, with polymeric dyes immobilized on paper or nylon membranes. Here arrays of 12 hydrophobic poly(p-phenyleneethynylene)s (PPEs), are assembled into a chemical tongue to detect/discriminate nitroarenes in water. The changes in fluorescence image of the PPEs when interacting with solutions of the nitroarenes were recorded and converted into color difference maps, followed by cluster analysis methods. The variable selection method for both paper and nylon devices selects a handful of PPEs at different pH-values that discriminate nitroaromatics reliably. The paper-based chemical tongue could accurately discriminate all studied nitroarenes whereas the nylon-based devices represented distinguishable optical signature for picric acid and 2,4,6-trinitrotoluene (TNT) with high accuracy.

Stabilizing Azaheptacenes.

The symmetrical 7,16-diaza-6,8,15,17-tetrakis(triisopropylsilylethynyl)heptacene was obtained by a Pd-catalyzed reaction of a 2,3-diamino-1,4-diethynylanthracene with a 2,3-dibromo-1,4-diethynyl anthracene. Positioning the TIPS-ethynyl groups adjacent to the central ring suppresses dimerization via [4+4] cycloadditions and Diels-Alder reactions; the middle pyrazine ring renders this species stable to oxidation. A single crystal structure was obtained, and thin film transistors with µn = 0.042 cm2 V-1 s-1 were produced. Transposition of the alkynyl groups into the 5,8,15,18-positions with a quinoxaline unit in the center of the heptacene decreases the stability, as does the introduction of two more nitrogen atoms into the 5,18-positions. The hydrocarbon 6,8,15,17-tetrakis(triisopropylsilylethynyl)heptacene is reasonably stable with a half-life of 25 h in solution. Four correctly placed TIPS-ethynyl groups protect heptacene cores.

Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies.

The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2.

Stabilization of Acenes: "Geländer"-Pentacenes.

We report soluble tetrakis-biphenylyl substituted pentacenes comprised of sp2 carbons and synthesized from pentacene-5,7,12,14-tetraone. Intramolecular Yamamoto coupling of two tetrakis(chlorobiphenylyl)pentacenes yields helical, doubly wrapped pentacenes, in which the quaterphenylene units solubilize the pentacenes and shield their central anthracene units to an unprecedented degree. The criss-cross-bridged pentacenes resist (photo)oxidation, Diels-Alder reactions and are much less reactive than TIPS-ethynylated pentacene. Extension of this concept might provide access to the larger acenes.

Thermolysis of Biphenylene toward Cyclo-ortho-phenylenes.

The solvent and catalyst free thermolysis of biphenylenes at 350 °C furnishes [n]cyclo-ortho-phenylenes ([n]COPs, n=4-10) in one step and in high yields. At 400 °C biphenylene dimerizes into tetraphenylene, but lower reaction temperatures produce cyclooligomers. If suitably substituted, the oligomers are soluble and can be isolated and characterized. The products are exclusively cyclic. In the crystalline state, [6]COP displays an alternating crown-shaped conformation.

Doubly Bridged Anthracenes: Blue Emitters for OLEDs.

The photooxidative stability of a series of doubly bridged anthracenes was evaluated after their preparation via twofold macrocyclization of a bis(resorcinyl)anthracene. Lightfastness correlates with the energy levels of the highest occupied molecular orbital (HOMO), resulting in superior stability of the tetraesters compared to the tetraethers. The lengths and steric demand of the linker only plays a minor role for the ester-based compounds, which can be prepared in reasonable yields and thus tested in proof-of-concept organic light-emitting diodes. Double ester-bridging allows deep blue electro-luminescence, highlighting the importance of the choice of the functional groups used for macrocyclization.

Elucidating Dynamics of Adenylate Kinase from Enzyme Opening to Ligand Release.

This study explores ligand-driven conformational changes in adenylate kinase (AK), which is known for its open-to-close conformational transitions upon ligand binding and release. By utilizing string free energy simulations, we determine the free energy profiles for both enzyme opening and ligand release and compare them with profiles from the apoenzyme. Results reveal a three-step ligand release process, which initiates with the opening of the adenosine triphosphate-binding subdomain (ATP lid), followed by ligand release and concomitant opening of the adenosine monophosphate-binding subdomain (AMP lid). The ligands then transition to nonspecific positions before complete dissociation. In these processes, the first step is energetically driven by ATP lid opening, whereas the second step is driven by ATP release. In contrast, the AMP lid opening and its ligand release make minor contributions to the total free energy for enzyme opening. Regarding the ligand binding mechanism, our results suggest that AMP lid closure occurs via an induced-fit mechanism triggered by AMP binding, whereas ATP lid closure follows conformational selection. This difference in the closure mechanisms provides an explanation with implications for the debate on ligand-driven conformational changes of AK. Additionally, we determine an X-ray structure of an AK variant that exhibits significant rearrangements in the stacking of catalytic arginines, explaining its reduced catalytic activity. In the context of apoenzyme opening, the sequence of events is different. Here, the AMP lid opens first while the ATP lid remains closed, and the free energy associated with ATP lid opening varies with orientation, aligning with the reported AK opening and closing rate heterogeneity. Finally, this study, in conjunction with our previous research, provides a comprehensive view of the intricate interplay between various structural elements, ligands, and catalytic residues that collectively contribute to the robust catalytic power of the enzyme.

Efficient Intramolecular Singlet Fission in Spiro-Linked Heterodimers.

We investigate intramolecular singlet fission (iSF) of spiro-linked azaacene heterodimers by time-resolved spectroscopy and quantum chemical calculations. Combining two different azaacenes through a nonconjugated linker using condensation chemistry furnishes azaacene heterodimers. Compared to their homodimers, iSF quantum yields are improved at an extended absorption range. The driving force of iSF, the energy difference ΔEiSF between the S1 state and the correlated triplet pair 1(TT), is tuned by the nature of the heterodimers. iSF is exothermic in all of the herein studied molecules. The overall quantum yield for triplet exciton formation reaches approximately 174%. This novel concept exploits large energy differences between singlet electronic states in combination with spatially fixed chromophores, which achieves efficient heterogeneous iSF, if the through-space interaction between the chromophores is minimal.

Rights and duties of genetic counsellors in Germany related to relatives at risk: comparative thoughts on the German Genetic Diagnostics Act.

Genetic testing has familial implications. Counsellors find themselves in (moral) conflict between medical confidentiality (towards the patient) and a potential right or even duty to warn at-risk relatives. Legal regulations vary between countries. English literature about German law is scarce. We reviewed the literature of relevant legal cases, focussing on German law, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This article aims to familiarise counsellors with their responsibilities, compare the situation between countries and point out legally unresolved areas.According to the German Genetic Diagnostics Act (Gendiagnostikgesetz) in case of an 'avoidable or treatable' genetic disorder, geneticists ought to confine themselves to the obligated advice to the patient. Whether a breach of the duty of confidentiality can be justified in exceptional cases by 'necessity as justification' for actively informing relatives at risk remains legally unclear. In case of a 'neither avoidable nor treatable' genetic disease, geneticists should also refrain from actively informing relatives as the justifiable state of emergency does not permit to break the duty of confidentiality.

Hexakis-TIPS-Alkynylated Nonacenes: Persistent and Processible.

Four substituted nonacenes were prepared and characterized by UV-vis and EPR spectroscopy and X-ray crystallography. The compounds are the most stable and soluble nonacenes to date - due to six strategically placed triisopropylsilyl(TIPS)-ethynyl groups. They are stable for several weeks in the solid state. In dilute solution their half-life is 5-9 h. Crystal structure analyses of two nonacenes prove their structures. A nonacene derivative was tested in a solution-processed transistor and exhibits ambipolar charge transport (µe =0.007 cm2 /Vs; µh =0.023 cm2 /Vs).

Dimerization of a Reactive Azaacene Diradical: Synthesis of a Covalent Azaacene Cage.

Two series of regioisomeric dicyanomethylene substituted dithienodiazatetracenes with formal para- or ortho-quinodimethane subunits were synthesized and characterized. Whereas the para-isomers (p-n, diradical index y0 =0.01) are stable and isolable, the ortho-isomer (y0 =0.98) dimerizes into a covalent azaacene cage. Four elongated σ-CC bonds are formed and the former triisopropylsilyl(TIPS) -ethynylene groups transformed into cumulene units. The azaacene cage dimer (o-1)2 was characterized by X-ray single crystal structure analysis and temperature-dependent infrared (IR), electron paramagnetic resonance (EPR, solid-state), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV/Vis) spectroscopies (solution) indicating reformation of o-1.

Etheno-bridged Azaacene Spiro Dimers.

We present the synthesis of two sets of spiro-connected azaacene dimers. Their geometry and electronic coupling are critically determined by a secondary linker, i. e., an etheno- and an ethano-bridge. The core fragment of the etheno-bridged dimer corresponds to a conformationally locked cis-stilbene. Optoelectronic properties, single crystal X-ray structures and stability with respect to oxidation of the conjugated and non-conjugated dimers are reported and compared. The conjugated dimers exhibit smaller optical gaps and bathochromically shifted absorption maxima, but are prone to unexpected oxygen addition, dearomatizing one of the azaacene substituents.

Second Generation of Cata-Annulated Azaacene Bisimides: Towards Electron-Accepting Materials.

This work presents the 2nd generation of cata-annulated azaacene bisimides with increased electron affinities (up to -4.38 eV) compared to their consaguine conventional azaacenes. These compounds were synthesized via Buchwald-Hartwig coupling followed by oxidation with MnO2 . Crystal structure engineering through variation of the bisimide substituents furnished crystalline derivatives suitable for proof of concept organic field effect transistors with electron mobilities up to 2.2×10-4  cm2 (Vs)-1 . Moreover, we were able to characterize the charge carrying species, the radical anion, using electron paramagnetic resonance and absorption measurements.

The Radical Anion and Dianion of Benzo[3,4]cyclobuta[1,2-b]phenazine.

We present the reduction of two azaacenes (a benzo-[3,4]cyclobuta[1,2-b]phenazine and a benzo[3,4]cyclobuta[1,2-b]naphtho[2,3-i]phenazine derivative), featuring a single cyclobutadiene unit, to their radical anions and dianions. The reduced species were produced using potassium naphthalenide in the presence of 18-crown-6 in THF. Crystal structures of the reduced representatives were obtained and their optoelectronic properties evaluated. Charging these 4n Hückel systems gives dianionic 4n + 2 π-electron systems with increased antiaromaticity, according to NICS(1.7)zz calculations, featuring unusually red-shifted absorption spectra.

Ring-Expanding Rearrangement of Benzo-Fused Tris-Cycloheptenylenes towards Nonplanar Polycyclic Aromatic Hydrocarbons.

Invited for the cover of this issue are Klaus Müllen and co-workers at the Max-Planck-Institute of Polymer Research and the University of Heidelberg. The image depicts the ring-expanding rearrangement of hexabrominated benzo-fused tris-cycloheptenylenes towards nonplanar polycyclic aromatic hydrocarbons. Read the full text of the article at 10.1002/chem.202203735.

Heterophenoquinones: Tuning Optoelectronics and Electrochromicity.

We report the synthesis and optoelectronic properties of 16 thiophene-based heterophenoquinones. These compounds were accessed in a convergent and modular approach, allowing for their efficient synthesis. Tuning of the optical band gap was achieved through π-extension by annulation of a benzene or tropone moiety to the thiophene, oxidation, change of the heteroatom or by attachment of a donor substituent to the thiophene core. The resulting compounds display intense colors covering the entire visible spectrum. We identified structure-property relationships and their impact on the HOMO and LUMO levels. Additionally, these materials change color upon reduction and according to in situ ultraviolet-visible-near infrared (UV-vis-NIR) and electron paramagnetic resonance (EPR) spectro-electrochemistry, they are promising electrochromes with cathodic color changes. Seven different electrochromic devices were constructed which all displayed a change in color upon reduction, demonstrating the potential of these new dyes in for example tintable glass.

Ring-Expanding Rearrangement of Benzo-Fused Tris-Cycloheptenylenes towards Nonplanar Polycyclic Aromatic Hydrocarbons.

A strongly twisted benzo-fused tris-cycloheptenylene, containing three dibenzosuberenone units fused to a common benzene ring, was subjected to Ramirez olefination and subsequent palladium-catalyzed Suzuki-Miyaura cross-coupling with 4-substituted phenylboronic acids. The high steric demand within the overcrowded, benzene-rich benzo-fused tris-cycloheptenylenes enforced an unprecedented 1,2-rearrangement upon π-extension during the Suzuki coupling reaction. According to crystal structure analysis, the resulting negatively curved polycyclic aromatic hydrocarbons consist of two heptagons and one octagon surrounding a central benzene ring as a result of strain release. In the solid state, the materials exhibit a blue to blue-green fluorescence with increased quantum yields and a hypsochromic shift of the emission maxima compared to their respective solutions.