UV filter benzophenone-2: Effects on zebrafish (Danio rerio) cytochrome P450.

Benzophenone-2 (2,2', 4,4'- Tetrahydroxybenzophenone; BP-2) is widely used as a sunscreen in Personal and Care Products (PCPs) for protection against ultraviolet (UV) radiation. The effects of BP-2 on random-sex adult zebrafish (Danio rerio) cytochrome P450 (CYP450) were studied. The main goal was to investigate the detoxification mechanisms underlying the adverse consequences of exposure to xenobiotic chemicals such as BP-2. Total protein content, CYP450 content, and erythromycin N-demethylase (ERND) activity were evaluated as indicators of protein CYP3A expression. Five sets of pooled random-sex adult zebrafish were exposed to 0.0, 0.1, 5.0, and 10.0 mg/L of BP-2 to evaluate their acute and chronic toxicity (4 and 15 days, respectively). ERND activity was significantly increased in the chronic toxicity group compared to that in the control group, whereas CYP450 remained unchanged. The results suggest a sufficiently fast catalytic process that does not alter the total CYP450 content. It implies a mediation of CYP450 3A induction by BP-2 and the pregnane X receptor ligand-binding domain (PXR LBD) interaction. Ligand-protein interactions were confirmed via in silico docking with AutoDock Vina. Further computational studies indicate BP-2 potential binding affinity for the Estrogen receptor alpha ligand binding domain (ERα LBD). These results suggest that CYPs effects may result in significant toxicity in the zebrafish. Our study highlights the importance of studying biomarkers in aquatic organisms to assess xenobiotic exposure and the potential toxicity of UV filters to humans.

Synthesis and characterization of low-dimensional N-heterocyclic carbene lattices.

The covalent interaction of N-heterocyclic carbenes (NHCs) with transition metal atoms gives rise to distinctive frontier molecular orbitals (FMOs). These emergent electronic states have spurred the widespread adoption of NHC ligands in chemical catalysis and functional materials. Although formation of carbene-metal complexes in self-assembled monolayers on surfaces has been explored, design and electronic structure characterization of extended low-dimensional NHC-metal lattices remains elusive. Here we demonstrate a modular approach to engineering one-dimensional (1D) metal-organic chains and two-dimensional (2D) Kagome lattices using the FMOs of NHC-Au-NHC junctions to create low-dimensional molecular networks exhibiting intrinsic metallicity. Scanning tunneling spectroscopy and first-principles density functional theory reveal the contribution of C-Au-C π-bonding states to dispersive bands that imbue 1D- and 2D-NHC lattices with exceptionally small work functions.

Toxicity of UV Filter Benzophenone-3 in Brine Shrimp Nauplii (Artemia salina) and Zebrafish (Danio rerio) Embryos.

The benzophenone (BP) family, including oxybenzone (BP-3), a prevalent sunscreen ingredient and environmental contaminant, has raised concerns since the year 2005. This study investigated oxybenzone toxicity in zebrafish (Danio rerio) eleutheroembryos and brine shrimp (Artemia salina) nauplii, focusing on the LC50 and developmental impacts. Zebrafish embryos (0.100-1.50 mg/L BP-3, 96 h) and A. salina (0.100-5.00 mg/L BP-3, 48 h) were tested with ultrasound-assisted emulsified liquid-phase microextraction (UA-ELPME) used for zebrafish tissue analysis. HPLC-DAD determined BP-3 concentrations (highest: 0.74 ± 0.13 mg/L). Although no significant zebrafish embryo mortality or hatching changes occurred, developmental effects were evident. Lethal concentrations were determined (A. salina LC50 at 24 h = 3.19 ± 2.02 mg/L; D. rerio embryos LC50 at 24 h = 4.19 ± 3.60 mg/L), with malformations indicating potential teratogenic effects. A. salina displayed intestinal tract alterations and D. rerio embryos exhibited pericardial edema and spinal deformities. These findings highlight oxybenzone's environmental risks, posing threats to species and ecosystem health.

Probing the range of applicability of structure- and energy-adjusted QM/MM link bonds III: QM/MM MD simulations of solid-state systems at the example of layered carbon structures.

The previously introduced workflow to achieve an energetically and structurally optimized description of frontier bonds in quantum mechanical/molecular mechanics (QM/MM)-type applications was extended into the regime of computational material sciences at the example of a layered carbon model systems. Optimized QM/MM link bond parameters at HSEsol/6-311G(d,p) and self-consistent density functional tight binding (SCC-DFTB) were derived for graphitic systems, enabling detailed investigation of specific structure motifs occurring in graphene-derived structures v i a $$ via $$ quantum-chemical calculations. Exemplary molecular dynamics (MD) simulations in the isochoric-isothermic (NVT) ensemble were carried out to study the intercalation of lithium and the properties of the Stone-Thrower-Wales defect. The diffusivity of lithium as well as hydrogen and proton adsorption on a defective graphene surface served as additional example. The results of the QM/MM MD simulations provide detailed insight into the applicability of the employed link-bond strategy when studying intercalation and adsorption properties of graphitic materials.

Regioselective On-Surface Synthesis of [3]Triangulene Graphene Nanoribbons.

The integration of low-energy states into bottom-up engineered graphene nanoribbons (GNRs) is a robust strategy for realizing materials with tailored electronic band structure for nanoelectronics. Low-energy zero-modes (ZMs) can be introduced into nanographenes (NGs) by creating an imbalance between the two sublattices of graphene. This phenomenon is exemplified by the family of [n]triangulenes (n ∈ N). Here, we demonstrate the synthesis of [3]triangulene-GNRs, a regioregular one-dimensional (1D) chain of [3]triangulenes linked by five-membered rings. Hybridization between ZMs on adjacent [3]triangulenes leads to the emergence of a narrow band gap, Eg,exp ∼ 0.7 eV, and topological end states that are experimentally verified using scanning tunneling spectroscopy. Tight-binding and first-principles density functional theory calculations within the local density approximation corroborate our experimental observations. Our synthetic design takes advantage of a selective on-surface head-to-tail coupling of monomer building blocks enabling the regioselective synthesis of [3]triangulene-GNRs. Detailed ab initio theory provides insights into the mechanism of on-surface radical polymerization, revealing the pivotal role of Au-C bond formation/breakage in driving selectivity.

Discussion paper: implications for the further development of the successfully in emergency medicine implemented AUD2IT-algorithm.

The AUD2IT-algorithm is a tool to structure the data, which is collected during an emergency treatment. The goal is on the one hand to structure the documentation of the data and on the other hand to give a standardised data structure for the report during handover of an emergency patient. AUD2IT-algorithm was developed to provide residents a documentation aid, which helps to structure the medical reports without getting lost in unimportant details or forgetting important information. The sequence of anamnesis, clinical examination, considering a differential diagnosis, technical diagnostics, interpretation and therapy is rather an academic classification than a description of the real workflow. In a real setting, most of these steps take place simultaneously. Therefore, the application of the AUD2IT-algorithm should also be carried out according to the real processes. A big advantage of the AUD2IT-algorithm is that it can be used as a structure for the entire treatment process and also is entirely usable as a handover protocol within this process to make sure, that the existing state of knowledge is ensured at each point of a team-timeout. PR-E-(AUD2IT)-algorithm makes it possible to document a treatment process that, in principle, does not have to be limited to the field of emergency medicine. Also, in the outpatient treatment the PR-E-(AUD2IT)-algorithm could be used and further developed. One example could be the preparation and allocation of needed resources at the general practitioner. The algorithm is a standardised tool that can be used by healthcare professionals of any level of training. It gives the user a sense of security in their daily work.

Engineering Small HOMO-LUMO Gaps in Polycyclic Aromatic Hydrocarbons with Topologically Protected States.

Topological phases in laterally confined low-dimensional nanographenes have emerged as versatile design tools that can imbue otherwise unremarkable materials with exotic band structures ranging from topological semiconductors and quantum dots to intrinsically metallic bands. The periodic boundary conditions that define the topology of a given lattice have thus far prevented the translation of this technology to the quasi-zero-dimensional (0D) domain of small molecular structures. Here, we describe the synthesis of a polycyclic aromatic hydrocarbon (PAH) featuring two localized zero modes (ZMs) formed by the topological junction interface between a trivial and nontrivial phase within a single molecule. First-principles density functional theory calculations predict a strong hybridization between adjacent ZMs that gives rise to an exceptionally small HOMO-LUMO gap. Scanning tunneling microscopy and spectroscopy corroborate the molecular structure of 9/7/9-double quantum dots and reveal an experimental quasiparticle gap of 0.16 eV, corresponding to a carbon-based small molecule long-wavelength infrared (LWIR) absorber.

Modelling bulk and surface characteristics of cubic CeO2, Gd2O3, and gadolinium-doped ceria using a partial charge framework.

The development and characterization of materials for solid oxide fuel cells (SOFC) is an important step towards sustainable energy technologies. This present study models cubic CeO2, Gd2O3, and gadolinium-doped ceria (GDC) using newly constructed interaction potentials based on a partial atom charge framework. The interaction model was validated by comparing the structural properties with experimental reference data, which were found to be in good agreement. Validation of the potential model was conducted considering the surface stability of CeO2 and Gd2O3. Additionally, the accuracy of the novel potential model was assessed by comparing the oxygen diffusion coefficient in GDCn (n = 4-15) and the associated activation energy. The results demonstrate that the novel potential model is capable of describing the oxygen diffusion in GDC. In addition, this study compares the vibrational properties of the bulk with density functional theory (DFT) calculations, using a harmonic frequency analysis that avoids the need for computationally expensive quantum mechanical molecular dynamics (QM MD) simulations. The potential is compatible with a reactive water model, thus providing a framework for the simulation of solid-liquid interfaces.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight. We aimed to identify genes that harbour rare variants that impact birth weight when carried by either the fetus or the mother, by analysing whole exome sequence data in UK Biobank participants. We annotated rare (minor allele frequency <0.1%) protein-truncating or high impact missense variants on whole exome sequence data in up to 234,675 participants with data on their own birth weight (fetal variants), and up to 181,883 mothers who reported the birth weight of their first child (maternal variants). Variants within each gene were collapsed to perform gene burden tests and for each associated gene, we compared the observed fetal and maternal effects. We identified 8 genes with evidence of rare fetal variant effects on birth weight, of which 2 also showed maternal effects. One additional gene showed evidence of maternal effects only. We observed 10/11 directionally concordant associations in an independent sample of up to 45,622 individuals (sign test P=0.01). Of the genes identified, IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (all fetal-acting) have known roles in adipose tissue regulation and rare variants in the latter two also showed associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG in both adipocyte differentiation and placental angiogenesis. NOS3, NRK, and ADAMTS8 (fetal and maternal-acting) have been implicated in both placental function and hypertension. Analysis of rare coding variants has identified regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, as well as further evidence for the role of insulin-like growth factors.

Bridging the information gap in organic chemical reactions.

The varying quality of scientific reports is a well-recognized problem and often results from a lack of standardization and transparency in scientific publications. This situation ultimately leads to prominent complications such as reproducibility issues and the slow uptake of newly developed synthetic methods for pharmaceutical and agrochemical applications. In recent years, various impactful approaches have been advocated to bridge information gaps and to improve the quality of experimental protocols in synthetic organic publications. Here we provide a critical overview of these strategies and present the reader with a versatile set of tools to augment their standard procedures. We formulate eight principles to improve data management in scientific publications relating to data standardization, reproducibility and evaluation, and encourage scientists to go beyond current publication standards. We are aware that this is a substantial effort, but we are convinced that the resulting improved data situation will greatly benefit the progress of chemistry.

Oxygen imaging of hypoxic pockets in the mouse cerebral cortex.

Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension (Po2) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for Po2 imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined "hypoxic pockets" and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.

Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case-control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes. RESULTS: The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m2). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10-12) and rs2228260 within XBP1 (P = 3.68 × 10-8). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10-6). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10-9) and a gene-based association was identified with ERBB4 (P = 1.59 × 10-6). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata. CONCLUSIONS: Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

Ecotoxicological Effects of TiO2 P25 Nanoparticles Aqueous Suspensions on Zebrafish (Danio rerio) Eleutheroembryos.

Among nanoparticles (NPs), titanium dioxide is one of the most highly manufactured worldwide and widely used in multiple products for both industrial use and personal care products. This increases the probability of release into aquatic environments, potentially affecting these ecosystems. The present study aimed to evaluate TiO2 P25 NP toxicity in zebrafish embryos and eleutheroembryos by evaluating LC50, hatching rate, embryo development, and chemical analysis of the TiO2 concentration accumulated in eleutheroembryo tissues. Zebrafish embryos ~2 h post-fertilization (hpf) were exposed to 75, 100, 150, 200, and 250 mg/L TiO2 P25 NPs for 48 and 96 h. A total of 40-60 embryos were placed in each Petri dish for the respective treatments. Three replicates were used for each treatment group. Ti4+ concentrations were determined by inductively coupled plasma optical emission spectrometry (ICP-OES), and a conversion factor was used to calculate the TiO2 concentrations in the tissues. The highest calculated concentrations of TiO2 in zebrafish larvae were 1.0199 mg/L after 48 h and 1.2679 mg/L after 96 h of exposure. The toxicological results indicated that these NPs did not have a significant effect on the mortality and hatching of zebrafish embryos but did have an effect on their development. LC20 and LC30 were determined experimentally, and LC50 and LC80 were estimated using four different methods. Up to 11% of embryos also presented physical malformations. These effects can be detrimental to a species and affect ecosystems. Physical malformations were observed in all treatments, indicating teratogenic effects.

Synthesis, Characterization, and Ecotoxicology Assessment of Zinc Oxide Nanoparticles by In Vivo Models.

The widespread use of zinc oxide nanoparticles (ZnO NPs) in multiple applications has increased the importance of safety considerations. ZnO NPs were synthesized, characterized, and evaluated for toxicity in Artemia salina and zebrafish (Danio rerio). NPs were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV-Vis) spectroscopy. The hydrodynamic size and stability of the ZnO NP surface were examined using a Zetasizer. Characterization techniques confirmed the ZnO wurtzite structure with a particle size of 32.2 ± 5.2 nm. Synthesized ZnO NPs were evaluated for acute toxicity in Artemia salina using the Probit and Reed and Muench methods to assess for lethal concentration at 50% (LC50). The LC50 was 86.95 ± 0.21 µg/mL in Artemia salina. Physical malformations were observed after 96 h at 50 µg/mL of exposure. The total protein and cytochrome P450 contents were determined. Further analysis was performed to assess the bioaccumulation capacity of zebrafish (Danio rerio) using ICP-OES. ZnO NP content in adult zebrafish was greater in the gastrointestinal tract than in the other tissues under study. The present analysis of ZnO NPs supports the use of Artemia salina and adult zebrafish as relevant models for assessing toxicity and bioaccumulation while considering absorption quantities.

Towards hybrid quantum mechanical/molecular mechanical simulations of Li and Na intercalation in graphite - force field development and DFTB parametrisation.

In this work a previously established QM/MM simulation protocol for the treatment of solid-state interfaces was extended towards the treatment of layered bulk materials enabling for instance investigation of metal intercalation in graphitic carbon materials. In order to study the intercalation of Li in graphite, new density functional tight binding (DFTB) parameters for Li have been created. Molecular dynamics (MD) simulations at constant temperatures (273.15, 298.15 and 323.15 K) have been carried out to assess the performance of the presented DFTB MD simulation approach. The intercalation of variable lithium and sodium content was investigated via z-distribution functions and analysis of the diffusivity in the direction parallel to the graphene plane. Both the calculated diffusion coefficients and the activation energy in case of lithium are in good agreement with experimental data. The comparison of the QM/MM MD simulation results provide detailed insights into the structural and dynamical properties of intercalated metal ions.

Mortality and major postoperative complications within 1 year after vascular surgery: a prospective cohort study.

INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short­term mortality. Prospective reports describing the incidence of long­term complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1­year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1­year follow­up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1­year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1­year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1­year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3­fold increase in 1­year mortality.

Prenatal treprostinil improves pulmonary arteriolar hypermuscularization in the rabbit model of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Pulmonary hypertension represents the major cause of neonatal mortality and morbidity. Prenatal diagnosis allows assessment of severity and selection of foetal surgery candidates. We have shown that treprostinil, a prostacyclin analogue with an anti-remodelling effect, attenuates the relative hypermuscularization of the pulmonary vasculature in rats with nitrofen-induced CDH. Here we confirm these observations in a large animal model of surgically-created CDH. In the rabbit model, subcutaneous maternal administration of treprostinil at 150 ng/kg/min consistently reached target foetal concentrations without demonstrable detrimental foetal or maternal adverse effects. In pups with CDH, prenatal treprostinil reduced pulmonary arteriolar proportional medial wall thickness and downregulated inflammation and myogenesis pathways. No effect on alveolar morphometry or lung mechanics was observed. These findings provide further support towards clinical translation of prenatal treprostinil for CDH.

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study.

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.

Five-Membered Rings Create Off-Zero Modes in Nanographene.

The low-energy electronic structure of nanographenes can be tuned through zero-energy π-electron states, typically referred to as zero-modes. Customizable electronic and magnetic structures have been engineered by coupling zero-modes through exchange and hybridization interactions. Manipulation of the energy of such states, however, has not yet received significant attention. We find that attaching a five-membered ring to a zigzag edge hosting a zero-mode perturbs the energy of that mode and turns it into an off-zero mode: a localized state with a distinctive electron-accepting character. Whereas the end states of typical 7-atom-wide armchair graphene nanoribbons (7-AGNRs) lose their electrons when physisorbed on Au(111) (due to its high work function), converting them into off-zero modes by introducing cyclopentadienyl five-membered rings allows them to retain their single-electron occupation. This approach enables the magnetic properties of 7-AGNR end states to be explored using scanning tunneling microscopy (STM) on a gold substrate. We find a gradual decrease of the magnetic coupling between off-zero mode end states as a function of GNR length, and evolution from a more closed-shell to a more open-shell ground state.