In vivo tumor targeting studies at 1 h 20 post-injection revealed specific tumor uptake of 1.89 ± 0.40%IA/g for the site-specific conjugate, 1.77 ± 0.29%IA/g for the random conjugate, no nonspecific organ targeting, and excretion via the kidneys and bladder. Both strategies allowed for easily obtaining 68Ga-labeled hPD-L1 Nbs in high yields. The two conjugates were stable and showed excellent in vivo targeting. Moreover, we proved that the random lysine-conjugation is a valid strategy for clinical translation of the hPD-L1 Nb, despite the lysine present in the CDR.Immune checkpoints, such as programmed death-ligand 1 (PD-L1), limit T-cell function and tumor cells use this ligand to escape the anti-tumor immune response. Treatments with monoclonal antibodies blocking these checkpoints have shown long-lasting responses, but only in a subset of patients. This study aims to develop a Nanobody (Nb)-based probe in order to assess human PD-L1 (hPD-L1) expression using positron emission tomography imaging, and to compare the influence of two different radiolabeling strategies, since the Nb has a lysine in its complementarity determining region (CDR), which may impact its affinity upon functionalization. The Nb has been conjugated with the NOTA chelator site-specifically via the Sortase-A enzyme or randomly on its lysines. [ Immune checkpoints, which mitigate immune activities under physiological conditions, can be hijacked by cancer cells, thereby overcoming the patient’s anti-tumor immune response. Amongst the immune checkpoints, programmed death-ligand 1 (PD-L1) and its receptor programmed death-1 (PD-1), have drawn the most attention during the last 10 years and monoclonal antibody (mAb)-based immunotherapies antagonizing PD-1/PD-L1 have revolutionized the cancer treatment paradigm . Recent Pre-clinical and clinical studies with radiolabeled mAbs showed that the assessment of the PD-L1 status by positron emission tomography (PET) imaging is a promising strategy for patient stratification ,12,13. H99mTc-labeled Nb revealed high signal-to-noise ratios, strong ability to specifically detect PD-L1 in melanoma and breast tumors, and surprisingly low kidney retention, unlike many other radiolabeled Nbs.Nanobodies (Nbs), also called single domain antibody fragments, can overcome limitations linked to the use of mAbs for PET imaging. Their high affinity and specificity, as well as their small size ~15 kDa), make Nbs ideal probes for molecular imaging. Their fast blood clearance allows for imaging as early as 1 h p.i. and radiolabeling with short-lived radioisotopes, lowering the radiation burden for the patients . We prev kDa, mak68Ga) , which is commonly used in clinical settings. To allow for chelation of 68Ga, Nbs are typically conjugated with the bifunctional chelating agent 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-NCS-Bn-NOTA) on the primary amino groups of the lysines of the Nb’s structure Ga-citrate solution was purchased from Mallinckrodt .All of the reagents and solvents were purchased from Sigma–Aldrich  or VWR . Buffers used for coupling reactions and for radiolabeling were prepared with metal free water  and purified from metal contamination using Chelex 100 resin. 4OAc Ph 7, at a flow rate of 0.8 mL/min. SEC purification of randomly functionalized Nb was performed on a Superdex Peptide 10/300 GL column while using 0.1 M NH4OAc pH 7, at a flow rate of 0.5 mL/min. For quality control (QC), radiochemical purity (RCP) was assayed with binderless glass microfiber paper that was impregnated with silica gel   using 0.1 M sodium citrate buffer pH 4.5–5 as eluent. RCP was also assayed by SEC on a Superdex Peptide 3.2/300 GL using a 2× Phosphate-buffered saline  at a flow rate of 0.150 mL/min. Serum and urine samples were analyzed on a Superdex 5/150 GL using 2× PBS at a flow rate of 0.3 mL/min.Size-exclusion chromatography (SEC) columns were purchased from GE Healthcare . SEC purification of the site-specifically functionalized Nb was performed on a Superdex 75 Increase 10/300 GL column using 0.1 M NH6-tag and/or a sortag (LPETG) and the Sortase-A enzyme were produced as described before GaCl3, obtained from [67Ga]Ga-citrate, as previously described Ga-NOTA-(hPD-L1) Nbs were obtained with a RCP > 99% and DC-RCY were 87 ± 5% (N = 3) and 86 ± 10% (N = 3), respectively, for a procedure time of 30 min.Besides labeling with 68Ga-labeled Nb remained > 99% after 4 h. After 4 h at 40 °C in injection buffer, 6% of a radiolysis side product was observed, showing an influence of temperature on the radiolysis process.In vitro stabilities of the radiolabeled probes are summarized in 68Ga]Ga-NOTA-(hPD-L1) Nb remained > 98% after 4 h of incubation.In the presence of 1000-molar fold excess DTPA, no transchelation was observed and the RCP of the site-specifically labeled Ga-NOTA-(hPD-L1) Nbs. For both probes, ex vivo analysis 1 h 20 p.i. showed very low uptake in all organs, except in the kidneys due to renal excretion. Notably, retention in the kidneys of the site-specifically labeled hPD-L1 Nb was 10.1 ± 2.4%IA/g, which is, to our knowledge, the lowest ever reported for a radiolabeled Nanobody at an early time-point.POS cells, or hPD-L1NEG cells as a control  than in the hPD-L1NEG tumors for the site-specifically radiolabeled Nb, and about five times higher (p < 0.0001) for the randomly radiolabeled Nb. Both probes showed high uptake variation in the hPD-L1POS tumors, which did not allow to conclude on a potential difference in affinity in vivo between the two radiolabeled Nbs. Using these preliminary data and taking into account variations in tumor size, a larger sample of animals (N = 21/group) was calculated to be necessary in order to make a statistically reliable conclusion. For both probes, the accumulation of radioactive signal in the hPD-L1POS tumors was measured: 1.89 ± 0.40%IA/g for the site-specifically radiolabeled Nb and 1.77 ± 0.29%IA/g for the randomly radiolabeled Nb , as depicted in Biodistribution and tumor targeting in athymic nude mice bearing hPD-L1The tumor-to-blood (T/B) ratio and tumor-to-muscle (T/M) ratio were calculated for both probes. T/B ratio for the site-specific Nb was 6.3 ± 3.0 (N = 21) and 5.4 ± 1.5 (N = 21) for the random Nb (NS). The T/M ratio for the site-specific Nb was 34.5 ± 13.2 (N = 21) vs. 28.0 ± 10.6 (N = 21) for the random Nb (NS).POS tumor cells confirmed the significantly higher (p < 0.0001) % of cells expressing hPD-L1 than the hPD-L1NEG tumor cells, as reported in Ex vivo flow cytometry characterization of the hPD-L1POS tumor and injected with site-specifically [68Ga]Ga-NOTA-(hPD-L1) Nb confirms the low background at 1 h 20 p.i. and high uptake in the tumor lesion . A smaller fragment could be observed at later time points (4 h) and it is most likely due to radiolysis, which is a result of combined positron emission and high temperatures FDG, implementation in routine patient care should also be very straightforward.Taking together all of the results obtained for each of the functionalization strategies, their high production yields, high purity, specific tumor targeting, and excellent tumor-to-background ratios make them both excellent candidates for future clinical translation. The site-specific coupling method offers the advantage that it yields a homogenous pharmaceutical product, which is not the case for the random lysine conjugation. Its implementation in a GMP radiopharmacy is however less straightforward as compared with the random strategy due to the use of an enzyme. Nevertheless, the use of enzymes in pharmaceutical productions is increasing, for example in antibody drug conjugate production for clinical trials, and such a development might also facilitate the use of the Sortase strategy for radiopharmaceutical production . Since t68Ga-labeled probe. We demonstrated that a lysine present in the CDR did not impact the affinity when randomly functionalizing this particular Nb with NOTA for 68Ga-labeling as compared with a site-specific strategy. Although the site-specific strategy had the advantage of providing a more homogeneous clinical product, the random strategy is more straightforward and less costly for clinical translation. The 68Ga-labeled Nb is a promising PET imaging agent for future clinical assessment of PD-L1 expression and patient stratification. When compared to other PET probes in development, the radiolabeled Nb shows the lowest kidney uptake, enables imaging at early time points after injection, and provides high tumor-to-muscle and tumor-to-blood ratios in a preclinical model, thereby confirming its high potential for successful clinical applicability in the future. In this study, we have confirmed the high affinity and specificity of a lead Nb targeting human PD-L1 as well as fast clearance in vivo of the Bridoux, J.; Broos, K.; Lecocq, Q.; Raes, G.; Keyaerts, M.; Devoogdt, N.; Breckpot, K.; Xavier, C. Human PD-L1-BINDING Immunoglobulins. hPD-L1 Nanobody No. PCT/EP2019/055133; WO/2019/166622; 6 September 2019. Keyaerts, M.; Devoogdt, N.; Raes, G. Radio-labelled Antibody Fragments for Use in the Prognosis, Diagnosis of Cancer as well as for the Prediction of Cancer Therapy Response. HER2-Nb imaging and therapy No. PCT/EP2015/067424; WO/2016/016329; 4 February 2016.


Ageism is unlike any other form of prejudice in that, all things being equal, we are all at risk of experiencing it as we age. Whilst this stands true, many communities experience discrimination in other domains such as gender, race, sexuality and disability. As these communities age they are likely to experience cumulative or intersectional disadvantage due to multiple stigmatized group memberships. Where it is understood that there are negative health  and psychological  outcomes associated with each form of discrimination, the often focused research is less than conclusive regarding the consequences of intersectional discrimination. Using both qualitative and quantitative methodologies from across the US, this symposium explores the impacts of ageism with regard to HIV status, disability status, race/ethnicity and LGBT identification. Exploring the intersections of ageism, each paper will highlight the challenges faced by the respective communities as well as some of the ways to address this using policy, practice and highlighting where additional research would be needed to fully understand the phenomena. Finally the discussant will summarise and collate ideas for a concluding panel discussion.


Background: We studied the effects of a supervised, structured exercise program in a severe sarcoidosis patient. Methods: After being clinically stable for two years, a 52-year-old woman  who originally had irreversible lung fibrosis, pulmonary arterial hypertension (PAH), mild mitral insufficiency, and atrial dilatation, and was candidate for lung transplant, performed a combined high-intensity interval, high load resistance, and inspiratory muscle training for 4.5 years, and was tested  every six months. Results: Cardiorespiratory fitness (CRF) and maximal pulmonary ventilation increased by 44% and 60%, respectively. Ventilatory efficiency also improved . She improved New York Heart Association (NYHA) class (from III to II), and cardiac alterations as well as PAH reversed so that she was not in need of lung transplantation anymore. Likewise, she suffered no more episodes of hemoptysis. Bone health was overall maintained despite the post-menopausal status and the corticoid treatment. Conclusions: A long-term combined exercise intervention safely contributed—at least partly—to improve CRF and NYHA class in a patient with severe sarcoidosis, suggesting a potential coadjuvant effect to attenuate clinical manifestations. Sarcoidosis is an autoimmune disease of unknown etiology , diagnosed in 2007 with the most severe presentation of systemic sarcoidosis according to the American Thoracic Society criteria—stage IV—indicating irreversible scarring in the lungs (pulmonary fibrosis) [The patient is a post-menopausal woman aged 52 years at the start of the study  , in the Beyond pulmonary involvement , she had ocular, dermal, and articular symptoms . She hasShe practiced athletics from the age of 17 to 20 years and adopted an essentially sedentary lifestyle since age 23 until starting our intervention—except for two 12-week respiratory rehabilitation programs performed 4 and 3 years, respectively, before the start of our exercise training intervention.All assessments were performed every 6 months (June and December) at the Exercise Physiology Laboratory at Hospital 12 de Octubre , which she first visited in June 2015. After we studied her medical history in depth (with one of us (A.L.) being a physician with solid expertise in the implementation of exercise interventions, including in-hospital programs, for patients with numerous disease conditions such as PAH ), she unFirst, we measured maximum inspiratory pressure (MIP) . Due to the history of recurrent hemoptysis (some during spirometry) and the fact that performing forced expiration is known to increase pulmonary capillary pressure , we refr2)  and gas exchange data  were continuously monitored. We followed a published protocol [2 decreased below 90%. Other criteria for test termination were chest pain, ECG signs of ischemia, severe dyspnea disproportionate to the effort, tachyarrhythmias, or a drop in BP. The protocol also included a recovery phase, during which the patient pedaled for one minute at 10 watts and one minute without resistance, before finally resting for one minute on the ergometer to prevent post-exercise desaturation. Gas-exchange parameters (10-s averages) where collected for the determination of the peak value of oxygen uptake (VO2peak) reached during the tests, as well as the ventilatory threshold (VT) and respiratory compensation threshold . The VT corresponded to the workload at which the ventilatory equivalent for oxygen (ventilation (VE∙VO2−1) starts to increase with no concomitant increase in the ventilatory equivalent for carbon dioxide (VE·VCO2−1) and with departure from linearity of VE. The RCP was determined as the workload at which both VE·VO2−1 and VE·VCO2−1 increase together with a decrease in end-tidal pressure of carbon dioxide [Thereafter, the patient performed a cycle ergometer  exercise test until volitional exhaustion, during which blood pressure (BP), heart rate (HR), 12-lead ECG, peripheral oxygen saturation  during and after each set of exercises.In the first visit only, the patient performed a circuit strength training session using basic machines , during which we monitored SpO1-L4) and femoral neck was performed as described [After the first year of training, we incorporated body composition analysis  to the battery of assessments. Body mass composition was calculated from a full body study scan, and a specific analysis of bone density in the spine (Lescribed .The patient underwent a combined (HIIT + high load resistance + IMT) program for a total of 4.5 years in her local fitness center under the supervision of a fitness specialist. The patient generally trained five to six days/week. This included two sessions of strength training using machines, two sessions of strength training using “functional exercises”, and two HIIT sessions. When she performed two sessions per day, this consistently included a HIIT and a functional training session, respectively.2 , and rating of perceived exertion  were recorded in each session. During the first three years all the sessions were performed on a cycle-ergometer . To prevent eventual abrupt decreases in SpO2 after exertion, each session ended with a cool-down phase . In the last phase (1.5 years) of the program, the HIIT sessions were performed on a treadmill . The transition from HIIT cycle-ergometer to HIIT treadmill sessions served two purposes: (i) to apply a more functional exercise modality with a greater transference to daily life activities; and (ii) to increase the impact load associated with exercise in order to prevent—or at least attenuate—the loss of bone mineral density that is known to be associated with both post-menopause and corticosteroid treatment [The HIIT program is detailed in reatment ,28.2 consistently >90%. Of note, this race speed was similar to the one corresponding to the active rest periods between intervals in the treadmill HIIT sessions  with SpOsessions .Strength training program is detailed in 2 were continuously monitored in all sessions, as was RPE, using the 0–10 OMNI Resistance Exercise Scale [2 above 90% . This combination was selected since high loads increase maximum force more than low loads [Thereafter, eccentric Russian belt squat  and, alsse Scale  at the eow loads , and a low loads .IMT was done using a mechanical pressure threshold device . It started with two sessions (morning and evening) of 10 maximum inspirations at 42% of MIP, five days a week, increasing gradually to 30 inspirations per session in the sixth month. Thereafter, the number of repetitions was maintained, and the inspiratory load was progressively increased depending on the patient’s intensity perception. She was asked to gradually increase the load of the inspiratory device so that it was always difficult, but not impossible, for her to do all the inspirations. After the second year, she performed two sessions of 60 inspirations per day, increasing the inspiratory load as described.2 dropped below 90% after the HIIT sprints, it consistently returned to baseline levels very quickly (within 10–15 s).During the study period the patient’s functional status improved from NYHA III  to II . At the end of 2016 and throughout 2017 several breaks in training occurred due to exacerbation of the disease likely associated with the progressive reduction in corticoid dosage  until the withdrawal of the drug in May 2017 and reintroduction again at the start of 2018 (due to exacerbation of symptoms) . In addi2 dropped below 90% it normalized very quickly (10–15 s).Strength training was affected by medication withdrawal in the same way as HIIT . Plantar2O). In addition to the interruptions of IMT due to the worsening of her condition after the medication withdrawal, IMT was suspended in March 2019 due to rib pain after a fall while running on the treadmill.The inspiratory load increased from 20 to 40 inspirations per day at 42% MIP of restriction to 120 inspirations per day at 85% of MIP, causing a 19% increase in MIP  at the start of the study to 8.3 MET at the end). This is an important finding because the VO2peak level reflects the synergistic action of pulmonary, cardiovascular and muscle tissue via a suite of physiological actions that effectively transport and deliver oxygen from the atmosphere to mitochondria in working muscles [2peak, is a strong prognostic factor of morbimortality, particularly in relation to cardiometabolic diseases [2peak above this level have a reduced cardiovascular risk [2peak was expressed in either absolute units (mL·min−1) or relative to body mass (mL·kg−1·min−1). Furthermore, the intervention was safe, with no persistent SpO2 drops or syncope episodes.The main finding of our study was that a combined (HIIT + strength + IMT) program, applied for 4.5 years in a patient with sarcoidosis (stage IV) and pulmonary involvement and treated with corticoids for 12 years, contributed—at least partly—to increase functional capacity (improving a class in the NYHA classification) as well as cardiorespiratory fitness  [2 drops in her daily life activities.HIIT induces both peripheral  and central (increased cardiac output) cardiovascular adaptations . Furtherubjects) . ImproveIMT has been shown to improve exercise capacity, functionality, respiratory muscle strength, dyspnea, and fatigue in patients with sarcoidosis . These i2peak (mL/min) and improving the patient’s NYHA functional class. The increase in maximum strength may have allowed her, at least partly, to maintain a higher training work rate and increase the ability to cope with—and adapt to—cumulative HIIT sessions. Resistance training is known to improve work economy [Resistance training may also have played a role in increasing the VO economy  and thus economy . Muscle  economy . Likewis economy , especia economy . Althoug economy . This is economy . In this economy . AlthougIt is widely known that bone and lean mass decrease with age, particularly in menopausal women due to hormonal changes . CorticoThe NYHA class improvement, together with the well-known deleterious effects of chronic corticoid treatment led to the progressive withdrawal of this drug after 1.5 years from the start of the training program. With the exception of the sarcoidosis flare-up caused by medication withdrawal, only one sarcoidosis-related hospital admission (due to respiratory infection) and one medical intervention (capsulotomy) related to sarcoidosis occurred in the 4.5 years. Adverse events related to training were a running fall from the treadmill  and plantar fasciitis. Despite these episodes, the patient maintained her adherence to the training program due to the positive impact that the improvement in QoL and wellbeing early during the intervention (in the first few months) had on her level of motivation, as well as to her strong self-discipline.The present study has several limitations that should be considered. First, as this is a case report, our preliminary results in only one patient must be interpreted with caution and cannot be generalized to all patients with sarcoidosis. In this regard, it would be interesting to conduct a randomized controlled trial with a long-term intervention like the present one, although this type of study might be very difficult to conduct. Second, the 1RM was not evaluated, and thus although an increase in load (kg) was observed with resistance training, we could not quantify the magnitude of the actual improvement in maximum strength. Finally, diet was not controlled.In summary, the results of this study suggest that a long-term combined (HIIT + strength + IMT) exercise intervention might have contributed, at least partly, to safely improve CRF and functional capacity (NYHA class) in a patient with severe thoracic sarcoidosis. Our results also suggest that the intervention could have acted as a coadjuvant treatment that helped to partially reduce the severity of associated pathologies (cardiac involvement and PAH) and attenuate the loss of BMD and muscle mass caused by menopause and chronic corticoid treatment. Randomized controlled trials are needed to confirm our preliminary findings.


We aimed to develop question prompt lists for family caregivers of nursing home residents with advanced dementia to augment advance care planning conversations. In the context of a joint European-Canadian study, we used standardized nominal group methods to create country-specific lists of questions. (Bereaved) family caregivers of persons with dementia read an information booklet about end-of-life care for people with dementia, and generated questions to ask healthcare professionals. They also marked the most important questions from pre-selected questions from other lists. In the Netherlands, 20 participants contributed to a question prompt list of 24 questions that gravitated towards questions about terminating life and the responsibilities of physicians and family involved in decision making. In Canada, 4 participants came up with a question prompt list of 15 questions, related mostly to staff-family communication, with some the same as selected in the Netherlands. Data from the other countries will be presented too.


An easily fabricated Fabry-Perot optical fiber humidity sensor with high performance was presented by filling Graphene Quantum Dots (GQDs) into the Fabry-Perot resonator, which consists of two common single mode optical fibers. The relative humidity sensing performance was experimentally investigated by an interference spectrum drift between 11 %RH to 85 %RH. 0.567 nm/%RH sensitivity and 0.99917 linear correlation were found in experiments that showed high sensitivity, good and wide-range linear responding. Meanwhile, its good responding repeatability was demonstrated by two circle tests with increasing and decreasing relative humidity. For investigating the measurement influence caused by a temperature jitter, the temperature responding was experimentally investigated, which showed its linear responding with 0.033 nm/°C sensitivity. The results demonstrate the humidity sensitivity is greatly higher than the temperature sensitivity. The wavelength shift influence is 0.0198 nm with 0.6 °C max temperature jitter in the experiment, which can be ignored in humidity experiments. The fast-dynamic responses at typical humidity were demonstrated in experiments, with 5.5 s responding time and 8.5 s recovering time. The sensors with different cavity lengths were also investigated for their humidity response. All sensors gave good linear responding and high sensitivity. In addition, the relation curve between cavity length and response sensitivity also had good linearity. The combination of GQDs and single mode optical fibers showed easy fabrication and good performance for an optical fiber relative humidity sensor. Relative humidity (RH) measurements are very important in chemical fields, industrial monitoring, agricultural, pharmaceuticals, environmental monitoring, and so on ,3,4,5,6.2 sputtering deposition was reported with 0.14 rad/%RH sensitivity [2O3-PVA composite films and got a maximum sensitivity of 0.587 nm/%RH, but the response linearity in a repeatability experiment was expected to be better. An optical fiber grating RH sensor was also reported, such as polymer-coated fiber Bragg grating [Many optical fiber humidity sensors with a different structure or sensitive materials have been developed in recent years. The optical fiber coated with Nafion-crystal was used to measure relative humidity from 40 %RH to 82 %RH in 1997 . In the sitivity . In 2019sitivity  proposed grating , which i grating . An arra grating . The LPG grating . Many re2 [Many kinds of optical fiber humidity sensors are fabricated by various materials coating at the periphery of fiber, such as graphene oxide (GO) , MoS2 [22 , poly  every 0.5 s. By analyzing the spectrum shift, we got the dynamic responding data of this humidity sensor. The peak wavelength shift results at a typical humidity value of 54 %RH, which is shown in As The F-P cavity parameters directly affect the interference spectrum, especially the cavity length. To investigate the influence on the humidity response, the humidity sensing experimental results are also obtained. Seven RH optical fiber sensors with a different cavity length are all evaluated. In experiments, the cavity length is 108.41 μm, 152.34 μm, 196.44 μm, 251.23 μm, 302.67 μm, 352.76 μm, and 405.23 μm, respectively. All the humidity responding curves are shown in As According to the previous comparison, this configuration has high sensitivity with good linearity, wide linear responding scale, easy fabrication, and a fast-dynamic response.An optical fiber Fabry-Perot relative humidity sensor composed of QODs and single-mode fibers has been fabricated and experimentally investigated. The interference peak wavelength shift can be tracked by MOI SM125 in the experiments. The humidity responding experiments have been operated in a wide humidity range (11 %RH–85 %RH), and given 0.567 nm/%RH sensitivity and 0.99917 linear correlation. The humidity measurements were repeated at two humidity changing circles, which showed its good responding repeatability. For investigating the influence caused by a temperature jitter, the temperature responding characteristic was also experimentally investigated. The temperature responding curve had 0.033 nm/°C sensitivity and 0.99787 linear correlation. The influence to wavelength shift is 0.0198 nm with a 0.6 °C max temperature jitter in the entire experimental process. The temperature responding sensitivity is greatly lower than the humidity. Furthermore, the sensor has a stable and fast dynamic humidity response, which was discovered through the dynamic measurement experiments. We obtained a 5.5 s responding time and an 8.5 s recovering time at 54 %RH. In short, this kind of sensor has high sensitivity, an easy fabrication process, low cost, a wide linear measuring scale, good repeatability, and a rapid dynamic response. Some applications need a high performance and low-cost relative humidity sensor. This sensor indicated the possibility of easy implementation.


Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet‐chemical non‐covalent functionalization of graphene with cationic π‐systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF‐SIMS. The charged π‐systems show a p‐doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p‐doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping. Organic star‐shaped tricationic molecules interact with graphene and a one‐electron transfer from graphene to the molecules leads to strong p‐doping. Both compounds were converted into trications 3+6 through N‐quaternization using alkylation agents to introduce various substituents and counterions . Due to the polar nature of the benzimidazole moiety and hydrogen‐bond acceptor function, it seems likely that water or methanol molecules can be adsorbed under ambient conditions. Although some contaminants are visible on the surface of the flakes of the r‐oxo‐G/hybrid the roughness and measured height is overall homogeneous after functionalization. Thus, the AFM results indicate that molecules form indeed films and do not cluster to aggregates.The non‐covalent modification of graphene was accomplished by incubating a silicon wafer with deposited graphene, either CVD graphene or r‐oxo‐G, in a 12 mx 150 μm of a film of flakes of r‐oxo‐G/3+8  was scanned in positive mode. The most prominent signal observed was m/z 811.16, which can be related to 3+8 through the loss of one of its counterions. As shown in Figure m/z signal all over the flake with almost constant intensity confirms the homogeneous non‐covalent functionalization of the r‐oxo‐G. In addition, no signal is found on the bare SiO2 surface, indicating that molecules are only adsorbed on the r‐oxo‐G flake.The existence of the tricationic molecules on the surface of r‐oxo‐G/hybrid was further studied by time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) analysis. The adsorbed tricationic molecules can be identified by ToF‐SIMS analysis. An area of 150 μm m/z 662.73 and m/z 513.28 corresponding to the mass of the trication without 2 and 3 counterions, respectively, . In addition, ToF‐SIMS was conducted in negative ion mode to detect the triflate counterion with m/z 148.95. The map of Figure ). However, experiments with a blank Si/SiO2 wafer as substrate reveals that the tricationic molecules are not adhering to the SiO2 surface . A Si/SiO2 wafer incubated in methanol also did not show signals from the trication molecules . An optical image of a functionalized r‐oxo‐G sample is included in the Supporting Information .Thus, these observations corroborate the height profiles obtained by AFM measurements. Also, although with lower signal intensity, signals were observed at 2 surface and on graphene surface.N‐methylbenzimidazolyl) benzene 3+8 on SiO2 substrate  or the reduced form 2+8,  on graphene computed on the density functional theory (DFT) level of theory support this interpretation . Reference Raman measurements on r‐oxo‐G/3+8 indicate, in agreement with the ToF‐SIMS results, that molecules are only adsorbed on the graphene flakes and not on the bare SiO2. Raman spectra recorded on CVD graphene and CVD graphene/3+8 reveals that 3+8 is adsorbed on graphene. Analysis of the shift of the position of the G peak, which is sensitive to doping,3+8, respectively . The influence of the solvent methanol on CVD graphene was investigated and did not show any significant influence on the G and 2D band . XPS was used to analyze the composition of the surface of r‐oxo‐G/hybrid materials.2‐hybridized character of the carbon present in graphene, together with minor contribution from certain oxidized states that cannot be completely avoided during the preparation.2‐intersurface in between the graphene layer and silicon substrate. The nitrogen (N) signal observed at 400 eV,3+7), oxygen (O) and sulfur (S),  or boron (B) and fluorine (F) . Comparison among the XPS spectra of pristine graphene, functionalized graphene and the neat molecules on silicon confirms the non‐covalent adsorption of the molecular systems on graphene. XPS samples with the neat molecules on substrates were prepared by drop casting a methanol solution of the respective tricationic molecule on a silicon wafer. The preparation of non‐covalently modified graphene was described previously.For this study, CVD graphene was used because its Raman peaks are sharper compared to the peaks for r‐oxo‐G. Thus, the choice of CVD graphene reduced the interfering overlap with other peaks in the subsequent analysis. Raman spectra from non‐covalently functionalized graphene show the presence of broad and overlapping signals between 1200–1600 cm+ Figure  C. We pr4 on silicon shows two binding energies for nitrogen at 398.6 eV and 400.5 eV  and a secondary amine type of nitrogen atom (R2‐NH). The binding energies for these two nitrogen atoms increase slightly to 399.0 eV and 401.0 eV, respectively, when the molecule 4 is adsorbed on graphene . It shows one major peak at the binding energy 402.1 eV, consistent with imidazolium nitrogen atoms.The XPS spectrum of the neat neutral molecule 3+7 and 3+11 on silicon, it could possibly correspond to an ensemble of tricationic molecules binding to the silicon surface in a distinctly different mode compared to the vast majority. On the other hand, the XPS spectrum obtained for the sample with the tricationic molecule 3+8 on CVD graphene shows one very broad signal that can be fitted by two components of equal intensity  what is consistent with the presence of two sets of nitrogen atoms. XPS analysis of the N 1s components reveals two species. Accordingly, the signal at around 399.7 eV corresponds to an iminium type state and the other component located around 401.7 eV agrees with the expected value for an imidazolium nitrogen state.As this minor peak is also present in the XPS spectra of tricationic molecules y Figure  B what i3+8 on silicon gives a ratio among fluorine, nitrogen and sulfur (F/N/S) of 3:2:1. This is in agreement with an assembly of one trication and three counterions, which corresponds to the molecular formula C36H33F9N6O9S3. After non‐covalent binding of 3+8 to graphene, this ratio changes to 1:3:0. The signal for the sulfur atoms is below the detection limit. The decrease of fluorine and sulfur, which originate from the triflate counterion, indicates that the triflate counterions become more exchangeable and possibly even superfluous.As will be discussed later, the two components may correspond to two various nitrogen atoms either facing or pointing away from the graphene. The change in the ratio of the N 1s signals also gives information about the doping of graphene by non‐covalently bound molecules. Both p‐3+7 and 3+11 on CVD graphene show similar trends . Charge transfer from graphene to the non‐covalently bound molecules could explain this observation. Due to the weaker Coulomb attraction, some of the counter ions could potentially be removed by rinsing the sample with methanol during the sample preparation, or exchanged by some negatively charged species in the methanol solvent, for example, methoxide ions. A summary of all tested molecules is depicted in Scheme 3+9 and 3+12 were investigated by cyclic voltammetry in acetonitrile . Both compounds show several reduction events. The first one‐electron reduction of 3+12 corresponds to a reversible one‐electron transfer at Ered,1=−1.65 V . Such long wavelength bands are usually a sign for the generation of radical species. Figure 3+12 and for the reoxidized species of 3+12. The uniform overlap of both spectra indicates that the same species was analyzed and that the first reduction event is reversible.The XPS data recorded for 3+8 (without counterions) on top of a 9×9 supercell of graphene served as the unit cell in our model system. Density functional theory with periodic boundary calculations was used to study the overall electron distribution in the system. The optimized geometry of 3+8 alone at the same level of sophistication is propeller shaped, characterized by an average dihedral angle of 53.2°  between the central benzene ring and the appended benzimidazolium moieties  of the unit cell  the peripheral benzimidazolium moieties. From a stabilizing point of view the effect of this partial electron transfer is twofold. First, the increased electron density at the central benzene ring decreases the coulombic repulsion between the cationic benzimidazolium moieties via a screening effect. Second, the bonding traits of the LUMO results in a planarization of the overall molecular structure when electron density is fed into the orbital. The later contributes favorably to the bonding interaction by allowing for a shorter bonding distance and an increase in the surface area exposed to graphene by the trication. The denser deposition of molecules in the physical samples compared to the unit cell explored in the calculations may disturb the system causing some molecules on the graphene surface to possess more 2+8 character and others to be more like 3+8. This could explain why the adsorbed molecules display broad/overlapping nitrogen signals in XPS. Another reason could be that the strong binding in combination with the propeller shaped molecular structure results in two chemically distinctly different sets of nitrogen: the set of three nitrogen atoms close to the graphene surface and the set of those on the molecular face opposite to the graphene surface. All six nitrogen atoms in the free cation are chemically equivalent and should, as observed for the pristine silicon/silicate substrate, only give one peak in XPS. The single main peak may in fact indicate that the interaction between the trication and the silicon/silicate surface is so weak that it does not significantly disturb the molecular properties.To identify the effect of electron transfer, calculations were performed with different overall charges  and the ionization potential of graphene (exptl. 7.20–7.30 eV). The mismatch between the two values justifies the partial transfer of charge (not a full electron) between graphene and trication in case of the 3+8 unit cell.The same LUMO orbital, responsible for the stabilization effect discussed for the 3+8 on graphene, r‐oxo‐G was used to fabricate a monolayer field‐effect transistor device (FET)  was constant at 10 mV. Transfer curves (dsI‐dsV) with unipolar character are shown in Figure 2 is observed after sweeping continuously from −50 to 50 V and then back to −50 V. From the dashed lines  of 28.6 cm2 V−1s−1 is obtained at ambient conditions, calculated by Equation To better investigate the p‐doping effect of ) Figure  A. In reoxC=1.15×10−8 F/cm−2. After doping r‐oxo‐G with 3+8dsI‐dsV curves still keep the unipolar character, but these curves lean to a higher p‐doped direction. The hole mobility decreased to 20.7 cm2 V−1s−1. In addition, we found that the hysteresis effect increased indicating that more carriers were trapped between r‐oxo‐G and the SiO2 interfaces. The resistance of monolayer r‐oxo‐G device (with length 3 μm) before and after doping varies only slightly from 6.0 to 5.8 kΩ with a channel width of 20 μm and length of 3 μm. To investigate the influence of the hysteresis on the carrier mobilities deeper, we calculated the carrier mobilities at different slopes for r‐oxo‐G and r‐oxo‐G/3+8, respectively, .in which 4 for non‐covalent functionalization of r‐oxo‐G also results in p‐doping of the underlying graphene  in Figure 4, compared with the measurements from 3+8. After doping with 4, the transfer curves become unipolar, suggesting a stronger p‐doping character of r‐oxo‐G. Hole mobility (hμ) of the r‐oxo‐G before and after doping decreases from 20.4 cm2 V−1 s−1 to 18.9 cm2 V−1 s−1. The corresponding resistance of the r‐oxo‐G before and after doping decreases from 27.2 to 18.9 kΩ at dsV=10 mV, bgV=0 V with a channel width of 10 μm and length of 4.5 μm. Comparing both FET devices with each other, a stronger decrease in hole mobility can be observed for 3+8. This can be explained by a stronger interaction between 3+8 and r‐oxo‐G compared with 4 and r‐oxo‐G, which leads simultaneously to a stronger p‐doping effect on the underlying graphene for 3+8.We note that the reference experiment using the uncharged compound e Figure  C. TransN‐hetero‐π‐systems, which were used to non‐covalently functionalize graphene forming graphene/molecular hybrid structures. The cationic molecules form a stable molecular layer and interact strongly with graphene. This results in a reversible one‐electron transfer between the molecules and the underlying graphene, which leads to p‐doping of the graphene. The functionalization of graphene and the one‐electron transfer was studied by AFM, XPS, ToF‐SIMS and Raman spectroscopy. The performed measurements did not show any influence of the various counterions. DFT‐calculations confirmed the observed effects from the performed experiments. With the reported wet‐chemical method of graphene functionalization, we were able to fabricate monolayer graphene FET devices. Comparing both FET devices with each other, a stronger decrease in hole mobility can be observed for the tricationic molecules 3+8 compared to the neutral precursor 4. This can be explained by a stronger interaction between 3+8 and r‐oxo‐G compared with 4 and r‐oxo‐G, which leads simultaneously to a stronger p‐doping effect on the underlying graphene for trication 3+8.Through a concise synthetic strategy, we synthesized a series of cationic Both the novel series of compounds as well as the described method help to understand the non‐covalent functionalization of graphene in more detail. In the future, novel sensors based on FET devices can be fabricated for selective sensing, if the analyte interacts with the cationic molecules adsorbed to the surface.The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Both complexes have a deprotonated hydroxyl group at neutral pH and electrode potentials representative of a stabilized trivalent iron center. The r1 relaxivity of the Fe(L1)(OH2) complex is double that of the saturated complex, Fe(L2), at 4.7 T, 37 °C in buffered solutions. However, variable-temperature 17O-NMR experiments show that the inner-sphere water of Fe(L1)(OH2) does not exchange rapidly with bulk water under these conditions. The pendant sulfonate group in Fe(L1)(OH2) confers high solubility to the complex in comparison to Fe(L2) or previously studied analogues with benzyl groups. Dynamic MRI studies of the two complexes showed major differences in their pharmacokinetics clearance rates compared to an analogue containing a benzyl ancillary group. Rapid blood clearance and poor binding to serum albumin identify Fe(L1)(OH2) for development as an extracellular fluid contrast agent. Complexes of Fe(III) that contain a triazacyclononane (TACN) macrocycle, two pendant hydroxyl groups, and a third ancillary pendant show promise as MRI contrast agents. The ancillary group plays an important role in tuning the solution relaxivity of the Fe(III) complex and leads to large changes in MRI contrast enhancement in mice. Two new Fe(III) complexes, one with a third coordinating hydroxypropyl pendant, Fe(L2), and one with an anionic non-coordinating sulfonate group, Fe(L1)(OH Nearly 40% of clinical MRI procedures use a contrast agent to produce enhanced images, and nearly all contrast agents are Gd(III) coordination complexes. Although Gd-based contrast agents are highly successful, there are concerns about potential toxicity and retention from long-term exposure, particularly for patients with renal insufficiency ,4,5,6,7.The Fe(III) complexes that were studied in the early years of MRI contrast agent development were not very effective in comparison to those of Gd(III) . In many6–108 s−1 for Gd(III) or Mn(II) complexes, with optimal rate constants of 107–108 s−1 at moderate field strengths of 3 T Cl for Fe(L1)(OH2) and [Fe(L2)]Cl2 for Fe(L2). The ligands and their protonation states, L1, H-L1 and L2, H-L2, are defined in Key steps in the synthesis of H-L1 and H-L2 are shown in −1∙cm−1 to 3800 M−1∙cm−1 (2) was estimated as 18.1% over 24 h and 53.6% over 72 h based on absorbance changes. For comparison, the dissociation of the Fe(L2) complex in acidic solution (100 mM HCl) was 7.9% over 48 h, and the dissociation of Fe(L3)(H2O) was 14% over 24 h and 38% over 72 h − anion (c-axis. Both monomers have a six-coordinate Fe(III) center with three amine groups and three pendant alcohol groups ° and 39.4(1)°, respectively (The Fe(L2) complex crystallizes in the non-centrosymmetric space group ]− anion . The chll groups . There aectively . Similarectively  .,59.17O-N17O resonance of water and the corresponding transverse relaxivity is low. However, Fe(L1)(OH2) presumably has one bound water ligand, but also shows little resonance broadening at neutral pH (17O resonance peak width of Fe(L3)(OH2) and Fe(L1)(OH2) reaches about 21% and 7%, respectively, of Fe(CDTA) at pH 3 (2), similar to our observations for Fe(L3)(OH2) Cl.+H The H-L1 ligand (0.100 mmol) was dissolved in ethanol (5.00 mL). Then, ferrous chloride tetrahydrate  was dissolved in ethanol (2.00 mL) and was added dropwise to the ligand solution. Fe(L1) complex was isolated as yellow solid  by precipitation with diethyl ether. Fe content was calculated through ICP-MS for [Fe(L1 + H+)Cl]Cl: 11.38%, found: 11.57% ± 0.01%. M: [Fe(L1)]+; LCQ-MS: found m/z 421.2 , m/z 443.2 (M + Na+ − H+), 30%), m/z 841.0 , and m/z 863.0 . FT-ICR-MS: calculated m/z 421.13341, found m/z 421.13273 , calculated m/z 443.11535, found 443.11460 . 2[Fe(L2)]Cl. The H-L2 ligand (0.100 mmol) was dissolved in ethanol (5.00 mL). Then, ferrous chloride tetrahydrate  was dissolved in ethanol (2.00 mL) and was added dropwise to the ligand solution. Fe(L2) complex was precipitated as yellow solid . The yellow solid complex was washed with diethyl ether. Fe content was calculated through ICP-MS for [Fe(L2)]Cl2: 13.08%, found: 12.85% ± 0.09%. M: [Fe(L2)]2+; LCQ-MS: found m/z 357.2 , m/z 713.1 , and 735.1 . FT-ICR-MS: calculated m/z 357.17150, found m/z 357.17820 , calculated m/z 713.33517, found m/z 713.33414 , calculated m/z 735.31711, found m/z 735.31576 .217O water solution and studied at variable temperatures (20–80 °C). 1/T2 was calculated by subtracting the full width at half maximum (FWHM) of the 17O resonance with Fe(III) complex from that in the absence of complex /kg. The Fe(III) complex stock solutions were adjusted to pH 7.2 by addition of meglumine and were injected intravenously via tail vein. MR data were recorded continuously for up to 1 h. Distribution studies and clearance kinetics were studied by using MR data acquired over several time points for up to 1 h, and additionally at 4 h and 24 h. For comparison, The Food and Drug Administration (FDA)-approved MRI contrast agent gadopentetate dimeglumine (Gd(DTPA), Magnevist®) and gadoterate meglumine (Gd(DOTA), Dotarem®) were injected at 50.0 μmol [Gd]/kg into separate group of mice and imaged as above. 2-H+][FeCl4]3 were grown through slow evaporation of solvent from a water/methanol mixture. Data were collected on a Bruker SMART APEX II CCD diffractometer. Data reduction was completed using SAINT version 8.40A, and a multi-scan absorption correction was applied using SADABS version 2016 included in the Bruker APEX3 software suite [2). Hydrogen atoms attached to oxygen atoms were located in the difference Fourier synthesis and had their distances restrained using the DFIX command to an effective O–H distance of 0.84 Å retrieved from the lst file. Anomalous scattering was used for absolute structure determination. The twist angles were calculated as torsion angles using the Olex2 software package [Single crystals of [Fe(L2)]re suite . Space-gre suite . The strre suite  using inre suite  using le package . Crystal1 relaxivity in phantoms at 4.7 T that we attribute to second-sphere water interactions, similar to an analogous complex with a benzyl ancillary group. The addition of an alkyl group with anionic sulfonate has the advantage that it produces a hydrophilic Fe(III) complex of high solubility. However, the replacement of a benzyl group with an alkyl group on the TACN macrocycle produces an Fe(III) complex that is less highly stabilized in the trivalent state. The hydrophilic nature of the Fe(L1)(OH2) complex combined with its relatively low binding to serum albumin leads to a complex that behaves as an extracellular fluid contrast agent. In fact, Fe(L1)(OH2) shows a pharmacokinetic profile that is similar to that of Gd(DTPA) or Gd(DOTA). Future research will focus on the molecular properties of Fe(III) macrocyclic complexes that contribute to serum protein binding and will explore factors that modulate biodistribution of the contrast agents.As shown here, Fe(III) macrocyclic complexes are promising for further development as MRI contrast agents. One of the macrocyclic Fe(III) complexes studied here demonstrates promising r


In the present study, well-designed nanohybrids are used to act as effective dual-function adsorbents for removing both anions and heavy metals from natural water, at the same time. In this trend, Zn-Al LDHs and graphene oxide are applied to build up building blocks to produce a series of nanohybrids. These nanohybrids were characterized by X-ray diffraction, thermal analyses, Fourier transform infrared spectroscopy, Raman spectroscopy, and scanning and transmission electron microscopy. These techniques confirmed that the prepared nanohybrids contained nanolayered structures with three–dimensional porous systems. These porous systems were identified by the nitrogen adsorption-desorption isotherms and water purification experiments. The obtained results indicated that these nanohybrids included suitable structures to act as dual function materials. The first function was achieved by removing more than 80% of both cadmium and lead from the natural water. The second function was accomplished by eliminating of 100% of hydrogen phosphate and bromide anions alongside with 80%–91% of sulfate, chloride, and fluoride anions. To conclude, these well-designed nanohybrids convert two-dimensional nanolayered structures to three-dimensional porous networks to work as dual-function materials for removing of heavy metals and different kinds of anions naturally found in the fresh tap water sample with no parameters optimization.  It is well known that the quality of drinking water plays an important role in public health of a community. Therefore, the chemical composition of surface water and groundwater, as sources of fresh water supply, is considered a critical issue for water quality . One of Recently, many beneficial processes such as electrocoagulation, sorption and electrochemical separation have been employed to remove several types of pollutants from aqueous mediums . HoweverTherefore, the current study focuses on designing dual-function materials to be effective for removing both anions and heavy metals at the same time from real water. These materials were built by combining two building blocks together into well-designed nanostructures. Layered double hydroxide (LDH) and graphene sheets are suitable as building blocks for producing the dual-function nanostructures.1−xMIIIx(OH)2]x+(A)n−x/n·mH2O, where MII and MIII are di-valent and tri-valent cations; respectively and An− is the interlayered anion [In one hand, LDHs are inorganic layered materials with a general formula of [MIIed anion ,13. In ted anion . LDHs maed anion . On the ed anion . The comGoh et al.  investigTherefore, the current study aims to prepare a set of dual-function nanohybrids to remove different kinds of inorganic anions and some heavy metals from natural water of the national network of Eastern providence of Saudi Arabia. These nanohybrids are based on the nanolayered structures of Zn-Al LDHs and graphene oxide. This target can be completed through marriage with two building blocks together into well-designed nanostructures. Certainly, layered double hydroxide (LDH) and graphene sheets are suitable for building blocks to produce the dual-function nanohybrids. In this trend, Zn-Al LDHs are prepared and doped by the prepared graphene oxide to build new micro-porous and meso-porous structures through growths of the nanolayers of LDHs on the nanosheets of graphene oxide. In order to maximize the efficiency of these nanohybrids, different percentages of graphene oxide are used to obtain the optimum percentage of graphene oxide for improving the texture of Zn-Al LDHs. Surface properties of the prepared nanohybrids are measured and compared with the pure Zn-Al LDHs. The prepared nanohybrids are also characterized by X-ray diffraction, Fourier Transform Infrared Spectroscopy and Raman Spectroscopy. In addition, a morphological study is investigated through scanning electron microscopy and transmission electron microscopy. The prepared nanohybrids are applied to remove monovalent anions such as: fluoride, chloride, and bromide alongside with di-valent and tri-valent anions such as sulfate and hydrogen phosphate from the natural water. In order to indicate the dual-function effect of the prepared nanohybrids, these materials are applied to remove the heavy metals (cadmium and lead) from the same water sample.Hence, based to the best knowledge of the authors, the current work would count as a pioneer study for applying nanohybrids as a dual-function adsorbent for removing different kinds of anions as well as cations such as heavy metals in real fresh water.The nanosheets of graphene were prepared by the electrochemical cell as shown in 3)2∙6H2O with 0.02 mol of aluminum nitrate hexahydrate Al(NO3)3∙9H2O in the presence of 0.05 mol of urea CO(NH2)2. This reaction was achieved in the presence of 0.11 g of the oxidized form of graphene suspended in 750 mL of deionized water. The reaction occurred at 80 °C in the water bath. The grey-white product was precipitated and washed several times by deionized water after 24 h.In order to avoid hydrophobic behavior of the graphene sheets, they were oxidized through the reaction with hydrogen peroxide in ultrasonic bath. A total of 0.6 g of graphene was suspended in 500 mL of water and 100 mL of hydrogen peroxide (30%) for 2 h. The nanohybrid (NH1) was prepared by the reaction of 0.05 mol of zinc nitrate hexahydrate Zn. Transmission Electron Microscopy  was carried out at room temperature with an acceleration voltage of 200 kV. Raman spectra measurements were performed using LabRAM HR Evolution, Horiba-Jobin Yvon Technology, with laser 633 ULF. The grating groove density was 300 grooves/mm. The methods of Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) were adopted to determine the material surface area, pore volume, and pore size distribution. Inductively coupled plasma emission spectroscopy  and ion chromatography  were employed to analyze the concentration of ions in solutions.The crystalline structures of Zn-Al LDH and the new nanocomposites were confirmed by X-ray diffraction ) by a scan rate of 0.5°/min. The functional groups were recorded through Fourier Transform Infrared Spectroscopy (FTIR) over the wave number range 400–4000 cmi and Cf (mg/L) is the initial and final concentrations of ions, respectively.The removal efficiency RE (%) of the samples was investigated at room temperature. Typically, a weight (g) of the sample was stirred in a volume V (L) of fresh tap water  at pH 6 up to 5 h to prepare constant concentrations W/V (10 g/L) of aqueous solutions. In order to study the effect of the adsorbent amount, two other concentrations (20 g/L and 30 g/L) were also used. Before achieving equilibrium, the concentrations of ions in solution were tested every hour. After equilibrium, the suspension was separated by centrifugation, and then the residual concentrations of cations and anions were determined by inductively coupled plasma mission spectroscopy (ICPE) and ion chromatography (IC) as shown in The crystalline structures of the prepared materials were determined by the powder X-ray diffraction technique as shown in The nanolayered structure of the prepared Zn-Al LDH was confirmed by the X-ray diffraction pattern shown in The X-ray diffraction patterns of the prepared nanohybrids NH1, NH2 and NH3 are displayed in By decreasing the content of graphene oxide to 2.5%, Due to continuous reduction of the graphene oxide content to 1.3%, three series of layered structures were observed in the X-ray diffraction of the nanohybrid NH3 as shown in The current data represented that graphene oxide played an important role for building up the nanolayered structure of the prepared nanohybrids. The nanohybrids NH1 and NH2 obtained one kind of nanolayered structure while three kinds of nanolayered structures were observed for the nanohybrid NH3. In order to explain this finding, we will discuss the dispersion of the nanosheets of graphene oxide during the growth process of LDH nanolayers. In the case of the nanohybrids NH1 and NH2, the high percentages of graphene oxide exist as groups when building up their nanolayered structures because of their aggregation behavior. It caused formation of one kind of combination between LDH layers with the nanosheets of graphene oxide. For the nanohybrid NH3, the low percentage of graphene oxide gave high dispersion in the medium. Therefore, their nanosheets exist as a single, few and/or groups. During growth of the nanolayers of LDH, three different kinds of interactions occurred with the nanosheets of graphene oxide while producing three different kinds of nanolayered structures. This description was confirmed by analyzing TEM images and surface measurement (will be discussed later).Another effect was observed for graphene oxide on the crystal size of the LDH layers because of the considerable broadened diffraction peaks of the prepared nanohybrids. Thus, the Debye–Scherer equation was applied to calculate the crystals size of the nanohybrids NH1, NH2 and NH3. According to the peaks of the planes 003, 006 and 009, the mean crystal size of the nanohybrid NH1 was calculated to be 17.0 nm. In case of both NH2 and NH3, they became 26.0 nm and 15.0 nm, respectively. However, the calculations of the pure Zn-Al LDHs showed that its crystal size was 74.40 nm. It highlighted that the presence of graphene sheets played vital role for production platelets of LDHs in the nano scale, which is in agreement with our previous studies for producing nanolayers of LDHs using carbon nanotubes .It is known that graphene consists of a two-dimensional structure. Therefore, SEM images of the prepared graphene exhibited plate-like morphology as shown in SEM images in By decreasing the content of graphene oxide, SEM images of the nanohybrid NH2 revealed very small aggregates looking like nanoflowers as shown in Energy-dispersive X-ray spectrometry (EDX) analysis indicated local data of the different elements in the outermost layers of the platelet of the nanohybrids. Zinc, aluminum, carbon and oxygen were clearly identified in the nanohybrids NH1 and NH3. It is known that graphene is a single layer of graphite. Consequently, TEM images of the prepared graphene revealed individual and multi-layers in the nano scale as shown in Due to the combination of graphene oxide with LDH, new structures of nanohybrids were released as presented in −1 reference to the structural defects and disorder graphitic carbon while, the second band recorded at 1600 cm−1 represented order graphitic carbon by confirming the existence of the hybrid sp2 atoms of carbon in graphene layers. By forming the nanohybrids based on the prepared graphene oxide, the main bands of graphene oxide were slightly shifted to lower wavenumbers for the nanohybrids NH1, NH2 and NH3. In case of the nanohybrid NH1, −1 and 1586 cm−1 by considering the presence of graphene sheets in the matrix of the layered structure of NH1. The observed shift for these bands indicates the strong interaction between the sheets of graphene oxide and the nanolayers of the LDH. New bands were observed at 1043 cm−1 and 516 cm−1. The new bands were due to M–O–C and M–O–M  [Raman spectroscopy is considered a well-known technique for exploring graphitic materials. l atoms) . It indil atoms) . The Fourier Transform infrared (FT-IR) spectroscopy was applied to compare between the function groups of the prepared LDH and the nanohybrids. The concentrations of some selected anions and heavy metals of interest for water quality were analyzed in a fresh sample of tap water from the domestic water network. The results of the analyzed sample were reported in −, HPO42−, F−, Cl− and SO42− as well as two heavy metals, (Cd and Pb). The behavior of these different anions to be adsorbed to the different materials prepared is illustrated in − and HPO42−. The removal efficiency (RE) of 100% was achieved with all types of nanohybrids NH1, NH2 and NH3. In contrast, adsorption by the parent structures of LDH was reported to be approximately 5% and 70% to HPO42− and Br−; respectively. The second attitude was noticed for both SO42− and Cl− ions. Their adsorption was poor (20%–30%) by the parent structure LDH, but gradually improved relative to increasing the amount of GO in structures prepared as well as increasing the W/V factor. However, the maximum RE% for SO42− and Cl− ions was calculated as ~80% for NH1 (W/V = 30 g/L). The obtained results by the current study showed enlargement in the removal percentage of the mentioned anions in comparison to the results concluded by Hatami et al. [The five different materials, previously mentioned, were examined for the water purification experiment GO, LDH, NH3, NH2, and NH1(a) with W/V = 10 g/L, while NH1(b) and NH1(c) were tested with W/V= 20 g/L and 30 g/L; respectively. Additionally, five anions were tested in a water sample for the following adsorption experiments: Bri et al.  who testLastly, the RE% for fluoride was 70% and 78% for GO and ZnAl-LDH (pristine structures) respectively, while it achieved up to 91% by the NH1 structure (W/V = 30 g/L). This result is higher than what was reported by Elhalil et al.  who mentHence, one can conclude that occurrence of GO alongside with LDH enhanced the removal efficiency of the tested anions naturally found in tap water. Moreover, it was observed that the modified materials NH1, NH2 and NH3 (same W/V =10 g/L) showed almost the same RE% for all anions studied. However, the nanohybrid NH1 with (W/V = 30 g/L) is highly recommended for the best anion removal from real water samples. The removal efficiency of two important heavy metals related to the water quality issue (Pb & Cd) was tested by applying all structures prepared as shown in The obtained results are in agreement with both Huang et al.  as well To sum up, the present effort would be recognized as a pioneer application for removal of both anions and heavy metals naturally found in a tap water sample by the prepared nanohybrids without experimental optimization. These results concluded that the prepared nanohybrids could work as dual function materials for elimination of different anions from the natural water as well as heavy metals at the same time.The current study applied the sheets of graphene oxide and the nanolayers of Zn-Al LDHs to produce well-designed nanohybrids to act as dual-effect adsorbents for removing different anions and two heavy metals from natural water. In this trend, these nanohybrids caused complete removal for sulfate and chloride anions. In addition, they removed the majority of fluoride, bromide and phosphate anions from the natural water. At the same time, these nanohybrids showed another positive effect for removal some heavy metals (cadmium and lead). It confirmed that the prepared nanohybrids can be used as dual-function nanohybrid materials for water purification. This dual-effect of the nanohybrids could be explained by creating new porous structures inside the materials prepared. In order to explain the behavior of the prepared nanohybrids toward removal of anions and heavy metals from natural water, the surface area and the porous structure of the nanohybrids NH1, NH2 and NH3 were studied and compared with the parent materials using Brunauer–Emmett–Teller (BET)  and Barr2/g as reported in 2/g. In the same trend, the surface area of both NH2 and NH3 became 61.50 m2/g and 60.3 m2/g, respectively. It means that the high efficiency of the nano hybrids can be due to the growth of the surface area. The porous structures of the nanohybrids were better than that of LDH because of new pores with a bigger size being created. The data in 3/g to the range of 0.08–0.290 cm3/g after combinating with graphene oxide. These pores were more suitable for trapping the different kinds of anions and heavy metals at the same time. These porous structures of the nanohybrids could be obtained by the nanolayers of LDH interacting with the nanosheets of graphene oxide, which act as a substrate for building the nanohybrids. According to our results, we conclude that the advantage of the dual-effect property of these nanohybrids enhanced the removal process of the different kinds of anions and the heavy metals from water in one stage only. It is likely the first time effective materials for eliminating of mono-valent, di-valent, and tri-valent anions were prepared alongside heavy metals in one step.The prepared nanohybrids represented high efficiency for removing five anions and two heavy metals even though the sizes of these species are different. This behavior was due to the sharp increasing of the surface area of the nanohybrids in comparison to pure LDH. The surface area of the pure LDH was 5.60 m


Search of new strategies for the inhibition of respiratory viruses is one of the urgent health challenges worldwide, as most of the current therapeutic agents and treatments are inefficient. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused a pandemic and has taken lives of approximately two million people to date. Even though various vaccines are currently under development, virus, and especially its spike glycoprotein can mutate, which highlights a need for a broad‐spectrum inhibitor. In this work, inhibition of SARS‐CoV‐2 by graphene platforms with precise dual sulfate/alkyl functionalities is investigated. A series of graphene derivatives with different lengths of aliphatic chains is synthesized and is investigated for their ability to inhibit SARS‐CoV‐2 and feline coronavirus. Graphene derivatives with long alkyl chains (>C9) inhibit coronavirus replication by virtue of disrupting viral envelope. The ability of these graphene platforms to rupture viruses is visualized by atomic force microscopy and cryogenic electron microscopy. A large concentration window (10 to 100‐fold) where graphene platforms display strongly antiviral activity against native SARS‐CoV‐2 without significant toxicity against human cells is found. In this concentration range, the synthesized graphene platforms inhibit the infection of enveloped viruses efficiently, opening new therapeutic and metaphylactic avenues against SARS‐CoV‐2. Present work shows that both electrostatic and hydrophobic interactions play a key role at the graphene/coronavirus interfaces and such materials can efficiently protect cells from coronavirus infections. While electrostatic interactions are responsible for the capturing of viruses, hydrophobic long alkyl chains can disrupt the envelop of the captured virions via hydrophobic interactions leading to a dual effect. SARS‐CoV‐2 belongs to the beta‐coronavirus genus. All coronaviruses have a lipid envelope with a capsid, which encapsulates the helical nucleocapsid with the RNA genome. The most prominent viral envelope component is the spike glycoprotein (S), which interacts with the angiotensin‐converting enzyme 2 (ACE2) on the surface of host cells and initiates virus entry, the first step of the SARS‐CoV‐2 infection cycle. Moreover, the polybasic cleavage site of S is found to play a crucial role in the binding between the virus and ACE2. Numerous efforts have been devoted to development of vaccines that generate neutralizing antibodies toward S to block viral interaction with ACE2. Similarly, the isolation and production of neutralizing antibodies targeting S promote the therapeutic treatment of SARS‐CoV‐2 infections, underscoring the importance of S as a target to block infection. However, it is also noticed that SARS‐CoV‐2 can mutate and it is conceivable that only small mutation of S by could render previously neutralizing antibodies ineffective. Therefore, it is essential to consider a new target instead of the S to develop materials for a broad‐spectrum inhibition of coronaviruses.SARS‐CoV‐2 poses a major threat to the public health worldwide, as it causes a respiratory disease named COVID‐19. Since the first case report in December 2019, a pandemic ensued with approximately one million deaths within the first nine months.1 SARS Hence, it is necessary to find a less toxic alternative for SARS‐CoV‐2 inhibition. Earlier reports have pointed out that negatively charged amphiphilic structures show broad‐spectrum inhibitory activity via the interaction with the viral envelope, including but not limited to herpes simplex virus (HSV), respiratory syncytial virus, human metapneumovirus, hepatitis C virus, ZIKA virus, etc. Surprisingly, in these studies with a fine tuning of charges and hydrophobicity, these compounds show low cytotoxicity but high virus inhibitory activity. The reason for such an observation could be due to the fast curing of membrane damages by self‐repairing mechanisms. Therefore, it is believed that the concept of envelope rupturing can be used to develop a robust SARS‐CoV‐2 inhibitor.Irreversible rupturing of the lipid viral envelope is a potential new approach for SARS‐CoV‐2 inhibition. Most of the surface‐active reagents, e.g., sodium dodecyl sulfonate, exhibit strong interactions with cellular membranes and can also rupture viral envelopes leading to inactivation of the virus, a so‐called virucidal compound. However, since they also act against the cellular membranes, they are highly toxic and can only be used for ex vivo disinfection of surfaces and hands.17 Hen Modified graphene nanoplatforms have shown significant inhibition of various pathogens due to their high binding affinity for bacteria and viruses. Even though the possible mechanisms of the interactions between graphene derivatives and pathogens are still a controversial topic, there are several suggested pathways for the antipathogenic action of these nanomaterials. Graphene materials are able to capture the pathogens by interactions with specific antibodies or ligands, electrostatic interactions, trapping or wrapping. Furthermore, graphene sheets can destroy the pathogens by hydrophobic or mechanical interactions. The versatility of nanoplatforms has been shown by their inhibition of various viruses, exemplified by designed inhibitors for HSV, African swine fever virus, alpha HSV, pseudorabies virus, and other viruses. In previous studies, graphene‐based compounds have been active against viruses mostly via a “binding and wrapping mechanism,” and have been virustatic inhibitors. Consequently, the virus is only temporarily inhibited from the interaction with host cells and the virus can escape from the inhibitor.Graphene, as a flexible 2D nanomaterial, is a promising candidate for the development of virus inhibitors due to the facilitated multivalent interactions at the functionalized interface.23 ModHerein, we report the development of graphene‐based virucidal compounds that rupture the envelopes of coronaviruses thus inhibiting viral infection irreversibly. The surface of graphene is functionalized with polyglycerol sulfate (PGS) and aliphatic chains of different length. In this study, we have investigated thoroughly how various sulfated graphene‐based materials interact with the virions of feline coronavirus (FCoV) and SARS‐CoV‐2 to explore the potential of designing virucidal graphene‐based inhibitors. A series of graphene platforms with PGS and alkyl amines of various chain lengths to surface of graphene is synthesized and compared for their inhibitory effect on coronaviruses. Functionalized graphene platforms that bear alkyl chains shorter than 10 carbon atoms show moderate infection inhibition without significant toxicity for cells. However, materials with longer aliphatic chains (>9 carbon atoms) indicate stronger inhibition and virion disruption of both coronaviruses, authentic SARS‐CoV‐2 and FCoV, but also exhibit higher toxicity for eukaryotic cells. Our results demonstrate a key role of electrostatics, i.e., polyglycerol sulfate coverage for virus capturing and a strong correlation between the length of alkyl chains and virucidal activity of such functionalized graphene‐based materials against coronaviruses.Figure x; x is the number of carbon atoms in aliphatic chains) were produced by our recently reported methods  . Each step of functionalization was proven using X‐ray photoelectron spectroscopy (XPS) due to the change in the elemental ratios both in survey and highly resolved C1s spectra . Afterward, alkyl amines with various length of chains were attached to the triazine functional groups of G‐PGS and graphene materials with dual alkyl amine/polyglycerol sulfate functionalities (G‐PGS‐Cx) were produced  proved successful attachment of polyglycerol and alkyl amines to graphene surface. To explore the impact of the length of aliphatic chains on the antiviral activity of graphene platforms, alkyl amines with a different number of carbon atoms  were conjugated to the surface of G‐PGS. The charge of the various graphene derivatives was not affected due to the attachment of alkyl chains  in comparison with G‐PGS (3.8 nm), according to the height and lateral size histograms of corresponding materials .In order to construct a platform for synergistic electrostatic and hydrophobic interactions with SARS‐CoV‐2 Figure 1a, graphs Figure .[23, ns Table –e, conju−1 considerably, the samples with shorter aliphatic chains (<10) did not show significant toxicity against the investigated cells lines , lung bronchial epithelial cells (HBE) and kidney Vero E6 cells was investigated by assessing the cells viability with the colorimetric assay Cell Counting Kit‐8 (CCK‐8). While samples with long aliphatic chains ≥10) reduced the cell viability at 50 µg mL0 reduceds  and G‐PGS‐C10 (9.8 ± 10.2 µg mL−1) . Therefore, material with the aliphatic chain length consisting of 11 carbon atoms showed the optimum values for the virus inhibition.Next, we studied inhibitory effects of the functionalized graphene platforms with FCoV, a coronavirus strain infecting cats. Though the S of FCoV and SARS‐CoV‐2 are slightly different, their envelope structures are similar, qualifying FCoV to be a surrogate to SARS‐CoV‐2 for inhibition studies. Plaque reduction assay showed dose‐dependent inhibition efficiency for the incubated compounds Figure 2a. In li1) Table . G‐PGS‐C−1) to quantitate virus replication  of 0.1, a procedure we refer to as pre‐infection treatment. After 24 h of infection, the cells were stained by anti‐FCoV antibodies to determine infection Figure –e. The nn Figure . Without−1, corresponding to an inhibitory effect higher than 99.9%. The cells also survived from the treatment, as the number of cells was not decreased, indicated by Hoechst 32 253 staining  were first incubated with the compounds a 1000 times higher concentration than their IC50 values for 1 h. After dilution to a concentration 10‐times lower than their IC50, the number of active virions was determined by plaque assay  were virustatic, the platforms with aliphatic chains ≥ 10  were virucidal. G‐PGS‐C11 was considered as the best material with two orders of magnitudes of virus titer reduction. The results of the plaque reduction assay and the virucidal assays showed that aliphatic chains more than 9 carbon atoms on the surface of graphene were necessary for virus membrane rupture  conditions, we used cryogenic transmission electron microscopy (cryo‐EM). Purified FCoV virions were incubated with G‐PGS‐C6 (virustatic) and G‐PGS‐C11  for 1 h and fixed by 2.5% formaldehyde. The samples were then cryofixated by plunge freezing and microscopically analyzed in a 200 kV TEM under low‐dose conditions Figure . Pristin and aliphatic chains interacted with the viral envelope  and FCoV IC50 for G‐PGS‐C11 were 42.6 ± 30.1 and 4.7 ± 0.7 µg mLmembrane.20 TheFigure −1, with a selectivity index (ratio of CC50 to IC50) of 86. Although G‐PGS‐C11 showed toxicity at high concentrations, the potent inhibition of SARS‐CoV‐2 at doses much lower than its CC50 value may allow safe antiviral treatment with this inhibitor. For example, G‐PGS‐C11 showed clear virus inhibition at 50 µg mL−1, a concentration where this compound did not show significant cellular toxicity. As shown in the image of the plaque reduction assays of Figure Finally, the inhibitory effect of the functionalized graphene platforms on authentic SARS‐CoV‐2 was studied using a plaque reduction assay Figure 4a,b. SimWe successfully synthesized graphene platforms with defined dual polyglycerol sulfate/aliphatic chains functionalities for SARS‐CoV‐2 binding and disintegration. In contrast with previously reported virustatic graphene‐based inhibitors, the synthesized inhibitors in this study were found to be virucidal. Virions bound to the functionalized graphene sheets by multivalent electrostatic interactions with the negatively charged PGS were disintegrated by the alkyl chains. Disruption of coronavirus envelopes occurred with elongation of aliphatic chains from G‐PGS‐C9 to G‐PGS‐C10 and showed the strongest inhibition and virucidality against feline coronavirus with G‐PGS‐C11. Therefore, alkyl chains should be long enough to exert efficient disintegration of the viral envelope. To rupture the envelop of the virus, the negatively charged PGS branches first interacted with the positively charged patches of the virion, then the aliphatic chains ruptured the membrane of the viral envelop. Graphene acted as a 2D platform to facilitate the interactions with virus particles. G‐PGS‐C11 displayed the most efficient antiviral properties against authentic SARS‐CoV‐2 without showing significant toxicity against eukaryotic host cells. The observed post‐treated effect and selectivity index of 86 opens the door for potential therapeutic applications.The compounds were 10‐fold diluted in Dulbecco's Modified Eagle's Medium (DMEM) and incubated with FCoV‐containing solutions with ≈100 PFU for 1 h at 37 °C. Afterward, the number of active virions was determined by plating the virus/compound mixture on a confluent monolayer of CRFK cells. Virus adsorption was allowed for 1 h before the supernatant was aspirated and replaced by a semi‐solid overlay of 1.3% methylcellulose (viscosity 400 cP). The overlay was removed after 48 h; cells were fixed with 4% formalin and stained with FCoV‐specific antibodies  to visualize plaques. The plaque reduction ratio was determined as following−1) were incubated with FCoV suspension containing ≈1 × 105 PFU for 1 h at 37 °C. Afterward, the mixture was diluted in DMEM medium 10‐foldly 5 times to an endpoint of no active virions. The number of active virions was determined by plaque assay and virus titers were calculated back by the respective dilutions.The functionalized graphene platforms  was propagated in Vero E6 cells and titrated via plaque assay.52 TheThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.


To the best of the knowledge, for the first time, macroscale superlubricity on macroscale surfaces under ambient conditions is reported. The mechanism of macroscale superlubricity is due to the combination of exfoliated graphene flakes and the swinging and sliding of the GCS, which is demonstrated by the experimental measurements, ab initio, and molecular dynamics simulations. These findings help to bridge macroscale superlubricity to real world applications, potentially dramatically contributing to energy savings and reducing the emission of carbon dioxide to the environment.Friction and wear remain the primary modes for energy dissipation in moving mechanical components. Superlubricity is highly desirable for energy saving and environmental benefits. Macroscale superlubricity was previously performed under special environments or on curved nanoscale surfaces. Nevertheless, macroscale superlubricity has not yet been demonstrated under ambient conditions on macroscale surfaces, except in humid air produced by purging water vapor into a tribometer chamber. In this study, a tribological system is fabricated using a graphene‐coated plate (GCP), graphene‐coated microsphere (GCS), and graphene‐coated ball (GCB). The friction coefficient of 0.006 is achieved in air under 35 mN at a sliding speed of 0.2 mm s A tribological system is developed using a graphene‐coated ball, graphene‐coated microspheres, and a graphene‐coated plate. Macroscale superlubricity is realized using the developed system on macroscale surfaces under ambient conditions. The fundamental mechanisms of macroscale superlubricity are elucidated by ab initio and molecular dynamics simulations. This was originally proposed by Hirano and Shinjo in 1990.2), argon (Ar), reactive hydrogen (H2), and humid air.−1.2) environment between the diamond‐like carbon and graphene films, through the formation of nanoscrolls of graphene flakes wrapping the nanodiamond particles during the sliding.Mechanical friction dissipates about one third to one half of the energy in the world, and around 80% of machine component wear.Graphene was found in 2004 with an atomic layer of graphite.2) surfaces, absent from the catalysts and post‐transfer techniques. PECVD dissociates methane (CH4) at 900 °C by radiofrequency power, forming the carbon (C) source of graphene. This does not need the metallic catalysts or conductive substrates as those used in traditional CVD. The fundamental mechanisms of macroscale superlubricity were elucidated by ab initio and molecular dynamics (MD) simulations.In this study, macroscale superlubricity was performed under ambient conditions on macroscale surfaces, which was conducted on a newly developed tribological system coated by multilayer graphene (MLG). The MLG were deposited by plasma enhanced CVD (PECVD) powered by radiofrequency at 900 °C on quartz and silica  as the carrier and protective gas. MLG coated microspheres (GCSs) conducted by PECVD are dispersed between the graphene‐coated ball (GCB) and graphene‐coated plate (GCP)  Figure c,d. The ) Figure .Figure2. GCP, GCS, and GCB were coated with MLG by PECVD simultaneously in a tube furnace, without metal catalysts and post‐transfer treatment, reducing effectively the fabrication processes and contaminations induced by traditional CVD techniques.2 or dust particles induced during preparation processes by the vendor. Raman spectra of GCP, GCS and GCB are drawn in Figure −1 correspond to D, G, and 2D peaks, respectively.2g phonon at the Brillouin zone center. The 2D peak is the second order of the D peak, which stems from a process where momentum conservation is satisfied by two phonons with opposite wave vectors. It is always present without the requirement of defects for its activation.IG/I2D), indicates a MLG structure on the coated surfaces,2 substrates. Under the same growth processes, the gain size is less than 160 nm on curved and rough surfaces.After graphene deposition, all the surfaces turn dark Figure2d–f, cFigure−1. The resolution and accuracy of the developed tribometer was 0.01 mN, and the maximum load was 1 N. In Figure −1. The dynamic videos of macroscale superlubricity under 35 mN at 0.1 and 0.5 Hz are displayed in Movies S1 and S2 in the Supporting Information, respectively. In Figure −1 for 1200 s under ambient conditions on macroscale surfaces. To identify the function of the MS, the friction coefficient of GCP/MS/GCP is shown in Figure S1 in the Supporting Information. Under 30 mN at 0.1 Hz, the average friction coefficient of GCP/MS/GCP is 0.017, and the friction coefficient decreases first from 0.04 to 0.016 under 50 mN at 0.1 Hz, then increasing sharply to 0.7. The experiments demonstrate that the MLG on curved and flat surfaces plays the decisive role for the robust macroscale superlubricity under ambient conditions.FigureFigure3. Wear rate, Ws is calculatedV, N, and S are the wear volume, normal load and sliding distance, respectively. The wear rate calculated is 4.3 × 10−4 mm3 N−1 m−1. It is difficult to identify the wear area without the marking shown with a red dotted circle in Figure −1 in Figure alculatedWs=  VNSalculatedWs=  VNSFigureE0 per atom increases monotonically from 0 to 8°  and the plate (p). The elastic modulus and Poisson's ratio are 73.3 GPar calculated is 331, 351, 370, 387, 402, and 417 nm under normal loads of 25, 30, 35, 40, 45, and 50 mN, respectively. This confirms that the adding of MLGCMS could reduce the contact area. The maximum calculated aspect contact pressures are 1.32, 1.41, 1.48, 1.55, 1.61, and 1.66 GPa for a GCS under loads of 25, 30, 35, 40, 45, and 50 mN, respectively. These pressures are higher than 1 GPa calculated in microscale superlubricity.Lateral force, describedE∗=  1  −3−1 for 1200 s. After sliding, the defects on the wear areas of GCB and wear tracks of GCP are improved by adding GMS, as confirmed by Raman spectra. The wear on GCB and GCP in the macroscale superlubricity system is the lowest, which is difficult to discern compared with other systems under the same sliding conditions. Ab initio and MD simulations were employed to elucidate the mechanism of superlubricity, according to the experimental conditions observed for macroscale superlubricity. It was found that the swinging and sliding of GCS plays a crucial role for the realization of superlubricity. Our results pave a way for the design and fabrication of high‐performance devices with macroscale superlubricity, as well as for energy savings and reduction of emissions to the environment.In summary, the GCB/GCS/GCP tribological system was fabricated simultaneously in a tube furnace by PECVD, in which there are no metal catalysts and post‐transfer process. Macroscale superlubricity was realized on a flat quartz plate coated by MLG under ambient conditions, in which the normal load varies from 25 to 50 mN at a sliding speed of 0.2 mm s4Ra, root mean square (rms), and peak‐to‐valley (PV) values were 0.87 ± 0.03, 1.09 ± 0.04, and 9.13 ± 0.65 respectively on the polished surface, as illustrated in Figure S9a in the Supporting Information. After deposition with MLG, the surface roughness was improved for Ra, rms and PV to 0.76 ± 0.04, 0.96 ± 0.05, and 8.90 ± 0.59, correspondingly . The error bars for surface roughness were due to the five measurements on the polished surfaces prior to and after growth of graphene.Quartz plates had a length of 15 mm, a width of 15 mm, and a thickness of 2 mm. Prior to deposition, all the quartz plates were machined in a polisher  by lapping, mechanical polishing (MP), and chemical mechanical polishing (CMP) sequentially. During lapping and polishing, the polishing pressure and rotation speed were 40.6 kPa and 80 rpm, respectively. The machining time was 3, 10, and 25 min for lapping, MP and CMP, respectively. Abrasive papers with a mesh size of 3000, polyurethane, and nubuck were used as the lapping, MP and CMP pads, respectively. Deionized water was the lapping solution. MP slurry consisted of 2 wt% alumina, 0.1 wt% sorbitol, and deionized water. CMP slurry was made from the MP slurry through adding citric acid to a pH value of 5.4. The developed machining processes and slurries for the quartz plates were efficient and environment‐friendly, respectively. Surface roughness 2 powder or MS  were made of quartz, and the diameter of balls was 4 mm. Balls and polished plates were ultrasonically cleaned in alcohol for 10 min, and then dried by compressed air. Balls, plates and powder were put in a tube furnace of PECVD  simultaneously to deposit graphene films. Prior to deposition, the tube furnace was evacuated for 8 min to a vacuum of 5 Pa. Then, the tube furnace was heated, and the temperature was increased to 900 °C within 50 min with a flux of H2 at 20 standard cubic centimeter per minute (sccm). When the tube furnace was at 900 °C, the temperature was kept constant for 10 min with a flux of H2 at 20 sccm. During the deposition of graphene films, the power of the plasma was 250 W, and the flux of CH4 and H2 was 16 and 20 sccm, respectively. The deposition time was 30 min. To ensure the uniformity of graphene on the SiO2 powders, the temperature and pressure of CH4 and H2 were kept constant at 900 °C, 16 and 20 sccm during the deposition, which was significant for the uniformity of deposited graphene. In addition, prior to deposition, the SiO2 powders were ultrasonically dispersed in alcohol and sprayed on the quartz plate. The dispersed SiO2 powders were heated at 60 °C for 5 min, and then they were put in the tube furnace of PECVD for deposition. After deposition, the PECVD system was turned off, and the temperature was allowed to naturally reduce to room temperature. Prior to and after deposition, photographs of balls, plates and powder were taken by a camera . Wear tracks and coated MLG were characterized and measured by a field emission SEM , confocal Raman microscope , TEM  and laser scanning confocal microscope . TEM samples of the MLGCB were prepared by focused ion beam technique . MLGCMS were ultrasonically dispersed in alcohol for 1 min, and then picked up by a Cu grid used for preparation of TEM specimens. TEM samples of the GCP were prepared manually. First, two GCP specimens were glued face‐to‐face, cut by an ultrasonic cutter to a disc of 3 mm in diameter , lapped by a disc grinder system , polished by a waterproof abrasive paper with a mesh size of 2000, thinned at the central area by a dimple grinder to a thickness of ranging from 10 to 30 µm , and finally thinned by a precision ion polishing system . Surface roughness was measured by a non‐contact surface profilometer .The balls  and SiOTribological tests were performed on a developed homemade tribometer.−5 eV, and a k‐point grid of 21 × 21 × 1 was employed to calculate the electronic structure. The cutoff energy of a plane wave was 500 eV. During the calculation of energy, the top layer of graphene was rotated for 40° from the initial equilibrium position, and the atoms were migrated stepwise for 40 steps until reaching the final positions.Ab initio calculations were carried out in the Vienna ab initio simulation package (VASP) using the projector augmented wave (PAW) method.r is the distance between pairs atoms.C‐Si, σC‐Si, and rC‐Si were 0.0096 eV, 3.0 Å, and 10 Å, respectively.−1. When touching the GNC, the downward movement of GCP was stopped. During sliding, the normal load was applied and consistently kept at 500 nN on the top GCP, NC and bottom GCP. Sliding was performed on the length direction of the GCP, and the speed and distance were 5 m s−1 and 5 nm, respectively.The GCP/GNC/GCP tribological performance was conducted by MD simulations. Both plate and NC were set as rigid bodies composed of a silicon single crystal. The two plates and NC were wrapped with four‐layer graphene to perform the superlubricity analysis, which was consistent with the macroscale superlubricity from the experiments. One‐layer graphene was fixed on the plate to simulate the coated MLG on the quartz plate during the experiments. Two‐layer atoms were fixed on two edges of the four‐layer graphene wrapped on two plates. For the four‐layer graphene wrapped on the NC, two‐layer atoms were fixed along the horizontal diameter. Each plate had a length of 44 nm, a width of 6.4 nm, and a thickness of 2 nm. The diameter of the NC was 6 nm. The four‐layer graphene on the plate had a length of 40 nm and a width of 6.4 nm. As the length of graphene was over six times that of the diameter of the NC, the boundary effect was effectively suppressed. The four‐layer graphene had a thickness of 1.035 nm, and the interlayer distance was 0.3445 nm. The interactions of C—C, Si—Si, and C—Si covalent bonds were simulated by the adaptive intermolecular reactive empirical bond order (AIREBO), Tersoff and 6–12 Lennard‐Jones (LJ) potentials, respectively.. The Ball, NS and plate were made of amorphous SiO2,2 were calculated by AIREBO and Tersoff potentials, respectively.2 interaction, and ε = 0.0024 eV, σ = 0.34 nm for graphene layers. The scratching simulations of GCB/GCP and GCB/GNS/GCP systems were performed with LAMMPS code, and visualized by AtomEye.To investigate the tribological properties with and without GNS, MD models were constructed on GCB/GCP and GCB/GNS/GCPThe authors declare no conflict of interest.Z.Y.Z. and Y.F.D. contributed equally to this work. Z.Y.Z. and D.M.G. conceived the projects. Z.Y.Z. wrote the paper. All authors commented on the manuscript prior to submission. Y.F.D. designed and performed the experiments of macroscale superlubricity. S.L.H. and S.Z.L. conducted the molecular dynamics simulations. L.L.C. and K.K.C. carried out the ab initio simulations. W.X.X. carried out the chemical mechanical polishing experiments. Z.Y.Z., Y.F.D., F.N.M., C.C.Z., Y.L., C.‐T.L., and I.P.P. analyzed the mechanisms of macroscale superlubricity. All authors discussed the results and commented on the manuscript.Supporting InformationClick here for additional data file.Supplemental Movie 1Click here for additional data file.Supplemental Movie 2Click here for additional data file.Supplemental Movie 3Click here for additional data file.Supplemental Movie 4Click here for additional data file.Supplemental Movie 5Click here for additional data file.Supplemental Movie 6Click here for additional data file.Supplemental Movie 7Click here for additional data file.