Saccharin is a commonly used artificial sweetener that exhibits both sweetening and sweet inhibition activities. The species‐dependent response towards saccharin and the interaction between saccharin and the sweet taste receptor T1R2/T1R3 remain elusive. In this study we used mismatched chimeras of T1R2 and T1R3 and calcium mobilization functional analysis to reveal a detailed species‐dependent response towards saccharin of human, squirrel monkey, and mouse sweet taste receptors. Our findings, combined with previous results by others, suggest multiple and complex interaction modes between saccharin and the sweet taste receptor, which are helpful guidelines for effective modulation of the sweet taste by sweetener/sweet inhibitors. Saccharin exhibits both sweetening and sweet inhibition activities. Besides the orthosteric binding site in T1R2 for activating the human sweet taste receptor T1R2/T1R3, it appears that there are at least two allosteric inhibitory sites located in T1R2 and T1R3 respectively to inhibit the receptor activity, suggesting multiple and complex interaction modes between saccharin and the heterodimeric sweet taste receptor T1R2/T1R3. CRDcysteine‐rich domainGPCRG protein‐coupled receptorHDheptahelical domainIDintracellular domainSEMstandard error of meanTMtransmembraneVFTMVenus flytrap moduleIt has been well‐known that the sweet taste perception in mammalians is broadly mediated by the sweet taste receptor, which belongs to the family C G protein‐coupled receptors (GPCRs) . The recThe heterodimeric sweet taste receptor T1R2/T1R3 is composed of three domains: a large extracellular domain, which includes a Venus flytrap module (VFTM) and a cysteine‐rich domain (CRD), a heptahelical domain (HD), which includes seven transmembrane helices (TMs 1–7), and an intracellular domain (ID), which interacts with the G protein  and sweet inhibitory (> 3 mm) responses, depending on the concentration of stimulation. Based on the species‐dependent responses towards Na‐saccharin and functional analysis of the human/rat chimeras of sweet taste receptor T1R2/T1R3, it has been suggested that the human T1R3 is the allosteric binding site for inhibition by Na‐saccharin [et al. reported that the extracellular VFTM region of human T1R2 is an orthosteric binding site for the sweetness of saccharin [The artificial sweetener saccharin has been shown to elicit both human sweet sensation  was purchased from Sigma‐Aldrich . Sucralose  was obtained from Tongyuan Sweetener Co. Ltd . Stevioside (purity ≈90%) was obtained from NuSci Institute & Corp . Saccharin  was obtained from Supelco . All other chemicals and reagents were analytical grade and were from Invitrogen .The human, squirrel monkey, and mouse T1R2s and T1R3s (mouse C57BL/6 strain) constructs were generated with the expression vector pcDNA3.1 (Invitrogen) as described previously . The Gα1http://swissmodel.expasy.org/) with the heterodimeric human metabotropic GABA(B) receptor (PDB: 6UO8) as the template. A sequence alignment of the human T1R2 and T1R3 and template sequences was carried out with the ClustalW program [The homology model of full‐length human T1R2/T1R3 was constructed using the Swiss‐Model program , but the responses were inhibited when the concentration of saccharin was above 3 mm. However, mouse receptor showed a dose‐dependent increase of response to saccharin and no inhibition was found at the concentrations of saccharin tested up to 60 mm. These results demonstrated the species‐dependent responses to saccharin for human and mouse but not squirrel monkey sweet taste receptors, while species‐specific inhibition of the response by saccharin at high concentrations (> 3 mm) for human but not mouse receptors.The constructs of sweet taste receptors and Gα16‐gust44 were transfected into the HEK293E cells, and their expression has been demonstrated in our and other previous studies , 13, 14.m saccharin. We selected three sweeteners: sucralose, stevioside, and d‐tryptophan, which can be perceived by all three species. As shown in Fig. m saccharin, whereas the response of mouse T1R2/T1R3 could not be inhibited. The dose–response experiment showed the inhibitory efficiency of the response towards sucralose by saccharin in human, squirrel monkey, and mouse  can inhibit the response of human but not mouse sweet taste receptor T1R2/T1R3 towards sucralose, stevioside, and D‐tryptophan, while the response of mismatched human T1R2 and mouse T1R3 (replacement of mouse T1R2 by human T1R2) towards these sweeteners can be inhibited by saccharin (> 3 mm). These results indicate that saccharin at high concentrations can bind at one or more allosteric sites located in human T1R2 to inhibit the response of human sweet taste receptor towards various sweeteners. However, it was previously described that the human T1R3 is an allosteric binding site of saccharin for inhibiting sweet taste [In this study we reported the detailed species‐dependent responses towards saccharin of human, squirrel monkey, and mouse sweet taste receptors both for sweetening and inhibitory activities, and revealed that the sweet taste receptor T1R2 is a novel allosteric binding site for inhibition by saccharin. As shown in Figs. et taste . Moreoveet taste , 8. Therm), Na‐saccharin preferentially binds into the high‐affinity orthosteric site in T1R2, activating the receptor. When the concentrations increase (>3 mm), the excessive saccharin molecules can bind to allosteric inhibitory sites located in human T1R2, and when more saccharin is added, they can probably bind with both T1R2 and T1R3, giving rise to the inhibited state of the receptor. Interestingly, we have reported that the HD of human T1R2 is an allosteric binding site for the sweet inhibitor amiloride [A two‐state allosteric model was proposed to explain the sweet “water‐taste” that removing the sweet taste inhibitors such as saccharin, acesulfame‐K, and lactisole located at the allosteric binding sites shifts the receptor from a high‐energy inhibited state to the constitutively active state, thus stimulating the sweetness upon water rinsing . Our premiloride . It is mThe authors declare no conflict of interest.The data are available from the corresponding author upon reasonable request.MC and BL conceived and designed the project, XZ and ML acquired the data, MC and BL analyzed and interpreted the data, and BL and MC wrote the article.


The title of Figure 2 should have read “Evaluation of Aortic Arch Anatomy in a Fetus With Suspected Aortic Arch Hypoplasia and Coarctation,” and the titles for Figures 5B, 5C, and 5D should have included “Fetal CMR.” In the Author Contributions section, the authors listed under Supervision should have been Arheden, Liuba, and Hedström. This article has been corrected.1In the Original Investigation titled “Utility of Fetal Cardiovascular Magnetic Resonance for Prenatal Diagnosis of Complex Congenital Heart Defects,”


To determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non‐regional lymph nodes (M1a) in daily clinical practice.The panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa . We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option.Consensus existed for 57% of the items. The panel agreed that prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA‐PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated.The Dutch consensus panel preferred PSMA‐PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high‐level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged. The selected approach combined the elements from the Delphi method, Nominal Group Technique, and consensus development techniques.2.2The panel consisted of representatives from all disciplines involved in the management of M1a PCa: urology (N = 10), medical oncology (N = 7), radiation oncology (N = 7), radiology (N = 4), and nuclear medicine (N = 9). Selection of panelists was based on clinical and scientific expertise in the field of PCa, geographic spread, and availability to participate in all parts of the study.2.3The first step consisted of an explorative survey on multiple statements and questions related to the definition and management of M1a PCa. The compilation of this survey was based on the clinical expertise of the Scientific Committee members and an explorative literature search for English‐language original and review articles published up to April 2020 using the National library of Medicine's PubMed database (H.B.). The search strategy included the following terms: “M1a prostate cancer,” “newly‐diagnosed M1a prostate cancer,” “de novo M1a prostate cancer,” “recurrent M1a prostate cancer,” “newly‐diagnosed low‐volume prostate cancer,” “de novo low‐volume prostate cancer,” “oligometastatic prostate cancer,” “oligorecurrent prostate cancer,”  AND “prostate cancer.” The abstracts of the retrieved records were screened to identify the most relevant articles. Relevant studies mentioned in the reference list of the identified articles were also taken into account. Additionally, meeting abstracts (2019‐2020) reporting on patients with de novo or recurrent M1a disease were included.2.4Definition○Anatomical level for non‐regional LNs for therapeutic decisions○Attribution of inguinal and pararectal LNs to M1a diseaseDiagnosis○Indications/appropriateness of imaging (techniques) to detect/assess metastases○Next steps after suspicion of metastases on imaging○Relevance of specific imaging parametersTreatment de novo M1a PCa○Curative intent of treatment and indications○Endpoints for clinical studies○Potential treatments and relevant parameters for treatment choiceTreatment M1a as recurrent disease○Potential treatments and relevant parameters for treatment choiceAll items included the option “Can't judge.”Panelists were asked to complete the explorative survey and provide suggestions for improvement. These survey results were shared with the panelists after which a video conference took place . Based on the survey results and the panel discussion during the video conference, a second survey with revised statements and questions was compiled and sent out to the panelists 1 week after the video conference. This survey contained six statements , and 15 multiple‐choice questions on the following topics:The complete survey is shown in the supporting information S1.2.5Strong agreement (consensus) and fair agreement were defined as the situation in which ≥ 75% or 50%‐74% of the panelists, respectively, chose the same option. If the option “can't judge” was chosen, the answer was excluded from the agreement calculations.3Consensus existed on 57% of the items (supporting information S2).3.1The TNM classification takes the iliac bifurcation as the anatomical inferior limit for M1a3.268Ga‐ or 18F‐radiolabeled‐PSMA‐PET/CT  was recommended by 97% of panelists, followed by wbMRI and bone scan ± SPECT/CT (both 11%) and conventional CT (5%). More specifically, PSMA‐PET/CT was considered most appropriate for the diagnosis of M1a disease in the initial and recurrent setting by  all panelists  > 20 ng/mL (92%), International Society of Urological Pathology (ISUP) grade ≥ 3 (89%), and ≥ cT3 (72%). Other factors were less chosen: ≥ cT2c (36%), ISUP grade ≥ 2 (3%), and a combination of lower staging factors 17%). As standard for initial metastatic screening of PCa, 7%. As st3.3There was almost consensus 74%) that treatment for de novo M1a may (sometimes) have a curative intent. A solitary LN and LNs below the aorta bifurcation were most frequently mentioned as a potentially curative condition Figure . Metasta% that tr44.1Although the TNM classification defines M1a as LNs outside the true pelvis ,4.2ISUP grade ≥ 3, PSA > 20 ng/mL and ≥ cT3 were considered the most common indications to perform imaging for metastatic screening. This is largely in line with the European Association of Urology (EAU) guidelines recommendations.4.3Opinions on treatment options for de novo M1a PCa  varied considerably and no consensus was obtained on a particular treatment option. Although the imaging modality for this question was unspecified, the majority of panelists may have given their opinion based on M1a disease detected on PSMA‐PET/CT as this imaging modality is widely used in clinical practice in the Netherlands. The expert opinions should be interpreted regardless of the underlying imaging modality. The variation in opinions on treatment options may (partly) be explained by the fact that currently available prospective data focus on low‐volume metastasized disease  which differs from M1a disease.P = .03).For M1a as recurrent disease, ADT alone was considered an option most frequently, followed by deferring treatment and local radiation of the M1a lesion. However, no consensus was obtained on a particular treatment option. The EAU guidelines recommend immediate systemic treatment in both asymptomatic and symptomatic metastatic patients.About two‐thirds of the experts expressed the opinion that de novo M1a disease might be curative, especially when only one solitary LN is involved. Using more sensitive imaging techniques like PSMA‐PET/CT, one might select and treat patients with better prognostic factors. However, the evidence of potential survival benefit is currently lacking. There was no agreement on which endpoint should be used in clinical trials investigating the management of M1a PCa. In the absence of prospective randomized trials, the panel believed that a large national registry is needed to prospectively collect the data of patients treated for M1a PCa.The absence of evidence from high‐quality clinical trials made the use of subjective opinions for many items around M1a management inevitable, which forms the most important limitation of this study. In conclusion, the panelists agreed that PSMA‐PET/CT is the preferred diagnostic modality to detect M1a PCa in both de novo and recurrent setting, but it is currently unknown if improvement in detection leads to better outcomes. Also, no consensus was obtained on the management of M1a PCa in daily practice. This may be a consequence of the scarcity of evidence from clinical studies and the lack of guidance for M1a PCa in the guidelines. In the absence of clinical prospective studies, a large national registry is needed to prospectively collect the data of patients treated for M1a disease.Dr Aluwini reports personal fees from Astellas, during the conduct of the study. Dr Oprea‐Lager reports other  from Astellas, during the conduct of the study; and an unrestricted grant from Janssen, outside the submitted work. Dr de Barros reports other  from Astellas, during the conduct of the study. Dr Mehra reports personal fees from Astellas, during the conduct of the study; grants and personal fees from Astellas, grants and personal fees from Janssen, personal fees from MSD, grants and personal fees from Pfizer, grants from Sanofi, personal fees from BMS, and personal fees from Bayer, outside the submitted work. Dr Stoevelaar reports other , during the conduct of the study. Dr van der Poel reports personal fees and non‐financial support from Astellas, during the conduct of the study.Supplementary MaterialClick here for additional data file.Supplementary MaterialClick here for additional data file.


Cervical sagittal balance is an important evaluation index of cervical physiological function and surgical efficacy. Subaxial kyphosis after atlantoaxial fusion is negatively associated with worse clinical outcomes and higher incidence of lower cervical disk degeneration.This study aimed to confirm the factors that influence subaxial lordosis loss after posterior atlantoaxial fusion.We performed a retrospective review of all patients following posterior C1–C2 fusion for atlantoaxial dislocation between January 2015 and December 2017. All charts, records, and imaging studies were reviewed for each case, and preoperative, immediate postoperative, and final follow-up plain films were evaluated. Comparing final follow-up and preoperative C2–C7 angle, patients were divided into two groups for further comparison: subaxial lordosis loss group and subaxial lordosis increase group.P < 0.05), but there was no statistical difference in other parameters. Univariate chi-square analysis showed that reduction in subaxial lordosis after posterior atlantoaxial fusion was associated with preoperative C2–C7 angle ≥ 20° . However, Logistic regression analysis showed that the preoperative C2–C7 angle ≥ 20° was not an independent risk factor .A total of 18 patients were included in the review, with an average radiographic follow-up of 8.4 ± 3.7 months (range 6–17 months). Subaxial lordosis loss was observed in 5 cases (27.8%) at the final follow-up, whereas 13 cases had an increase in subaxial lordosis. The cervical sagittal parameters of preoperative and final follow-up between two groups were compared, the preoperative C2–C7 angle of the subaxial lordosis loss group was bigger than the subaxial lordosis increase group (27.6° ± 10.5° vs 10.5° ± 10.5°, Our study demonstrates that subaxial lordosis loss may occur after posterior atlantoaxial fusion, and preoperative C2–C7 angle ≥ 20° was a risk factor of postoperative loss of subaxial lordosis. Atlantoaxial dislocation (AAD) is a rare disorder of the craniocervical junction characterized by C1–C2 instability and loss of normal articulation. It is often associated with complex deformities of the craniovertebral junction and poses a significant risk of neurological deterioration .Posterior atlantoaxial fusion is the main surgical method for the treatment of atlantoaxial dislocation. It has achieved good clinical results and fusion rate . HoweverCervical sagittal balance, an important evaluation index of cervical physiological function and surgical efficacy, has received increasing attention recently . StudiesFollowing institutional review board (IRB) approval, we evaluated the retrospectively collected single-institute database of patients who had posterior atlantoaxial fusion for atlantoaxial dislocation between January 2015 and December 2017. Among those patients, we applied the following inclusion criteria to identify the study cohort: (1) patients diagnosed with atlantoaxial dislocation, (2) patients with Wang classification [Applying these criteria yielded a total of 18 patients that were included in our final analysis. There were 8 males and 10 females with an average age of 49.6 ± 13.7 years (range 25–72 years). Among the patients, 15 had transverse ligament loosen, 2 os odontoideum, and 1 rheumatoid polyarthritis. The study is a retrospective radiographic analysis.Types I and II atlantoaxial dislocation were relatively easily fixed and fused in the reduced position from a posterior approach. Through a midline incision, we exposed the posterior arch of the atlas and the lamina of C2. The vessels and nerve roots of C2 were pulled caudally. The junction between the lateral mass and the inferior arch of C1 was exposed. Then we visualized and palpated the pedicle of C1. A point was opened with a burr. The pedicle of C1 was prepared with a 2.5-mm drill bit. After tapping a 3.5 mm pedicle screw  was inserted into each pedicle. Next, the vessels and nerve roots of C2 were retracted cephalad to expose the superior and internal aspect of the isthmus of C2. The C2 pedicle screw  was drilled, tapped, and inserted using the technique described by Abumi et al. . Two rodRadiologic evaluation included standard lateral view of radiographs in a neutral position, which was taken preoperatively, immediate postoperatively and at final follow-up. For every patient, two senior authors performed the measurements twice independently. Measurements were performed using Cobb’s technique .C0–C2 lordosis was measured as the angle between the McGregor line and lower endplate of C2. The measurement of C1–C2 lordosis was calculated between a line connecting the anterior tubercle to the posterior margin of the C1 spinous process and the inferior end plate of C2. C2–C7 lordosis was defined as the Cobb angle between the lower endplates of C2 and C7. C0–C7 angle was measured as the angle between the McGregor line and lower endplate of C7. The C2–C7 sagittal vertical axis (SVA) was measured as the distance from the posterosuperior corner of C7 and the vertical line from the center of the C2 body. The T1 slope (T1S) was the angle formed by the tangent to the upper endplate of T1 and the horizontal reference line. The neck tilt (NT) was defined as an angle formed by a line drawn in the upper end of the sternum and a line connecting the center of the upper endplate of T1 and the upper end of the sternum. The thoracic inlet angle (TIA) as an angle formed by a line from the center of the T1 upper end plate vertical to the T1 upper end plate and a line connecting the center of the T1 upper end plate and the upper end of the sternum  and subaxial lordosis increase group (n = 13). The subaxial lordosis loss group included the patients whose final follow-up C2–C7 angle was reduced compared with preoperative C2–C7 angle, while the subaxial lordosis increase group included the patients whose final follow-up C2–C7 angle increased.At the last follow-up, patients were divided into two groups for further comparison: subaxial lordosis loss group .The t test was used to compare the pre-operative and final follow-up cervical sagittal parameters, and compare the cervical sagittal parameters between two groups before operation and final follow-up. Binary logistic regression was used for continuous data, and Cochran and Mantel–Haenszel chi-squared tests were used for dichotomous data. Univariate and multivariate logistic regression analyses were used to identify potential risk factors. Multivariate logistic regression was performed using variables with P > 0.05).A total of 18 patients were included in the review, with an average radiographic follow-up of 8.4 ± 3.7 months (range 6–17 months). Overall, subaxial lordosis loss was observed in 5 cases (27.8%) at the final follow-up, whereas 13 cases had an increase in subaxial lordosis. The comparison of the cervical sagittal parameters between pre-operation and final follow-up is shown in Table P < 0.05), but there was no statistical difference in other parameters . However, logistic regression analysis showed that the preoperative C2–C7 angle ≥ 20° was not an independent risk factor . These results are illustrated in Tables The cervical sagittal parameters of preoperative and final follow-up between two groups were compared, the preoperative C2–C7 angle of the subaxial lordosis loss group was bigger than the subaxial lordosis increase group , indicating that there may be other factors affecting the postoperative loss of subaxial lordosis. Limitations of the study include the small sample size, lack of long-term follow-up. Furthermore, whether postoperative pain or muscle stiffness has an impact on the results needs to be further clarified.Toyama et al.  found thIn conclusion, our study demonstrated that subaxial lordosis loss may occur after posterior atlantoaxial fusion, and preoperative C2–C7 angle ≥ 20° was a risk factor of postoperative loss of subaxial lordosis. To avoid postoperative cervical malalignment for patients with atlantoaxial dislocation, more attention should be paid to fully consider the age, etiology and other factors before surgery, determine the appropriate atlantoaxial fixation angle and surgical technique.


NORD (NO relaxation delay) NMR spectroscopy is introduced. The idea is to design concatenated experiments in a way that the magnetization used in the first relaxes toward equilibrium during the second and vice versa, thus saving instrument time. Applications include complete well‐resolved 1H‐1H and 1H‐13C one‐bond and long‐range correlation maps of an 80 mM solution of a trisaccharide recorded in less than two minutes and hydrocortisone with extensive spectral overlap.The novel concept of  NORD (NO relaxation delay) NMR spectroscopy is introduced and combined with concatenation of experiments in a way making relaxation delays unnecessary and thus enhancing overall sensitivity. Alternatively, an initial excitation angle larger than π/2 aligns the saved magnetization along the −z axis, so that the spin echo π pulse turns it to the +z axis as desired. Such ideas were used in the early days of 13C editingThis concept is in principle also applicable to complex NMR pulse sequences consisting of several pulses and delays, but it is in general not straightforward to “save” some of the initial magnetization for succeeding repetitions of the pulse sequence. An exception is where a spin echo with an excitation and a refocusing pulse is involved. If a smaller than π/2 flip angle is used for excitation the “saved” magnetization will be inverted by the refocusing pulse, so an additional π pulse is needed at the end to align the saved magnetization with the positive NORD, NO Relaxation Delay. The idea is to have a pulse sequence containing for example, two modules representing individual experiments and laying out the overall pulse sequence such that the pool of magnetization used in the first module relaxes toward equilibrium during execution of the second and vice versa. In that way, there is no need for the usual recovery delay and instrument time can be saved.This Communication demonstrates how the concept of the Ernst angle can be implemented in an efficient pulse sequence for heteronuclear correlation and implements that solution into a new concept dubbed Clearly, if the modules of the overall pulse sequence affect different spin isotopes, the solution is trivial, so the interesting case is where the modules involve the same spin isotopes, and also in a way that excludes discrimination of spins based on selective pulses.The current work builds on recent papers on concatenated pulse sequences consisting of modules arranged so that they share a common and necessary recovery delay.1H magnetization not attached (the I pool) or attached (the IS pool) to 13C, respectively, and the BANGO pulse sequence elementTwo different pools of magnetization are involved in the experiments, namely π-βI2xI-12JIS-πxI,S-12JIS-π-βI2xII pool by a flip angle βIand inverts the IS pool by a π rotation. (Superscript on the pulse angle parentheses indicates I or S spin rf channel and subscript indicates phase.) The 1H π pulse later in the HMBC or SEA XLOC modules realigns the IS pool with the +z axis, and when βIis set in the range π2<βI<πthat is also the case for the “saved” I pool magnetization.excites the IS pool. In their original forms they saturate both the I and the IS pool and thus make a recovery delay necessary before the next scan. Hence a modification that more or less leaves the I pool invariant and saves some of the IS pool magnetization is needed for NORD.This is all pretty straightforward but the challenge arises with the succeeding 2BOB or H2OBC module using the 1H channel the element π2x-T2-πx-T2-π2ywhere T is set for homonuclear coherence transfer according to pertinent JHH (15–25 ms). Right before the second π/2pulse the relevant product operators are in phase magnetization, Iy, in both pools and singly antiphase magnetization, -2I1xI2z, in the IS pool.The initial part of 2BOB/H2OBC pulse sequences contains on the π/2ypulse is perfect in the IS pool, because it leaves Iyinvariant to yield one‐bond correlation peaks and transforms -2I1xI2zinto 2I1zI2xrepresenting two‐bond correlation. However, to save some magnetization for the next scan a compromise pulse phase different from yis needed to turn a fraction of Iyinto -Iz. That would also work for Iyin the I pool but for these more slowly relaxing spins it is highly beneficial to avoid the phase compromise.Disregarding NORD, the π/2excitation pulse in 2BOB/H2OBC by a BIG‐BIRD version out of the following subclass:The BIG‐BIRD pulse sequence elementπ/2yand a π/2vrotation in the I and IS pools, respectively, as can be verified by a vector model analysis. The one‐ and two‐bond correlation peak intensities are proportional to cosvwhilst the saved IS pool magnetization is proportional tosinv. The saved I pool magnetization is not compromised for any setting of v, because all in‐phase magnetization (now present as Ix) is converted to -Izby the last π/2yIpulse.It acts as a 1H spectra of the methyl group in sodium acetate with about 2/3 13C enrichment. The central 1H{12C} resonance is clearly unaffected by the setting of the angle v. In contrast, the doublet of methyl protons attached to 13C shows an increasing phase shift as vis decremented from 900 to 00 ending up with a π/2phase difference between the I and IS pools of magnetizations. It is a curious fact that the flip angle and the phase of the first pulse in the applied BIG‐BIRD element are always identical.Figure 1). The experiment performed without recovery delay between scans included only 1 scan per t1 increment. To enhance resolution the non‐uniform sampling strategy[t1 dimension. The resulting H2OBC and HMBC spectra acquired in record time of 1 min 48 s are shown in Figure 1H and 13C assignment according to the “assignment walk” shown in the H2OBC spectrum. The sequential order of the sugar residues is verified by the interglycosidic three‐bond 1H‐13C connectivities observed and indicated in the HMBC spectrum in Figure The proposed NORD strategy has been implemented in the two‐module BANGO HMBC‐H2OBC experiment  and tested on a trisaccharide . A shorter constant‐time delay in the H2OBC module will raise the HMBC enhancements.Compared to separate HMBC and H2OBC experiments the NORD approach applied to 1 [1] across the spectra and it is an option to attempt evening out such variations by appending an isotropic mixingDMSO) exhibiting several overlapping resonances in both the proton and the carbon spectrum.NORD SEA XLOC‐HMBC‐2BOB was tested on hydrocortisone (2 and 2B CH2) are color coded and overlaid in Figure 1H and protonated 13C, including the completely overlapped ones, as for example, C14‐(H14/H15a), C8‐(H8/H7a), C7‐(H7a/H8), and C15‐(H15a/H14) framed in boxes . The “assignment walks” are indicated by arrows in the spectra. Moreover, the assignment of all quaternary carbons including two‐ and three‐bond distinction is achieved by analysis of HMBC and SEA XLOC spectra obtained in the same concatenated NORD experiment, which thereby completes the assignment of all proton and carbon resonances in hydrocortisone. These HMBC and SEA XLOC spectra with two‐ and three‐bond distinction are included in ESI .These overlaps are largely resolved by 2BOB editing into four subspectra, that is, separate one‐ and two‐bond spectra each edited according the number of attached protons being odd or even. These spectra of hydrocortisone  NMR spectroscopy has been introduced in combination with concatenation of two or three experiments delivering complete heteronuclear correlation maps within minutes for small molecules. Future perspectives include concatenation of other and possibly more experiments allowing longer time for spin system recovery. That can well require development of other building blocks than BANGO and BIG‐BIRD used in this paper. Finally, it remains to be seen to what extent current and future complex NMR experiments in general can be designed or modified according to the NORD principle to exploit the concept of the Ernst angle. Where it is possible, there is potential for sensitivity gain and reduction in instrument time.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.


Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in France in 1992 as a 3 + 1 scheme at 2, 3, and 4 months (primary vaccination) with a booster at the age of 16–18 months. The vaccination was simplified in 2013 to a 2 + 1 scheme at 2 and 4 months (primary immunization) and a booster at the age of 11 months. The coverage was 95.4% in France at 24 months in 2017. During the period 2017–2019 the number of Hib invasive infections increased with several cases of vaccine failure.n = 130) and  was used.The numbers and proportions of Hib invasive isolates during the period 2017–2019 were compared and vaccine failure cases were explored. A seroprevalence study was performed by measuring anti-polyribosyl-ribitol phosphate (PRP) IgG concentrations by ELISA among children < 5 years of age at the time of sampling covering the periods of the 3 + 1 or 2 + 1 schemes of Hib vaccination. A collection of residual 232 sera was tested (group 3 + 1 Anti-PRP IgG concentrations were significantly higher in toddlers of 2 years (median 2.9 μg/ml) in the 3 + 1 group while these concentrations showed a median of 0.58 μg/ml among children in 2 + 1 group. The proportion of children of 2 years of age who achieved 1 μg/ml threshold (56%) was higher in the 3 + 1 group than that observed in the 2 + 1 group (25%). All the detected cases of vaccine failure received the 2 + 1 scheme and anti-PRP IgG levels were less than 1 μg/ml at the admission. However, these levels increased significantly 1 month after the admission suggesting a secondary immune response to the Hib infection.The simplification of the vaccination to a 2 + 1 scheme seems to reduce the level of anti PRP IgG. Hib antibodies wane rapidly after the 11 months booster and may not be enough to ensure long term protection. Surveillance of cases and monitoring of titres need to be continued to inform future vaccination policy. Haemophilus influenzae (Hi) is a Gram negative bacterium that can be capsulated or non-capsulated. The structure of the capsule polysaccharides allows dividing the capsulated isolates into six distinct serotypes (Hi a to f) while non-capsulated isolates correspond to non-typeable isolates (NTHi). Hi is a commensal resident of the respiratory and the genital mucosa. Asymptomatic carriage of Hi in healthy children under 5 years is common (27.7%) varying between 73.2% in winter and 26.8% in summer [Haemophilus influenzae b, and hepatitis B). In 2017, the vaccine coverage was estimated at 95.4% at the age of 24 months (https://www.santepubliquefrance.fr/determinants-de-sante/vaccination/donnees. Accessed 14/03/2020).n summer . Hi isols common 7.7% varys common 7.7% varyNeisseria meningitidis serogroup C as protective titres fell to 36% 18 months after vaccination [Streptococcus pneumoniae [. For example, after primary vaccination at 2, 3, and 4 months of age, antibody levels that were measured at 8, and 11 months declined for serotype 4 below the seroprotection level of 0.35 μg/ml [In France, in 2017, NTHi represented 75% of invasive Hi isolates while Hif and Hib represented 10 and 7% respectively. However, 50% of the Hib cases were among children < 5 years old and represented 13% of Hi cases among children < 5 years . The prohttps://pubmlst.org/hinfluenzae/ through filtering by country (France) and serotype (b) to allow retrieving of WGS sequences in FASTA formats as well as the ENA accession numbers.Surveillance of IHiD was previously reported with a case definition that relies on the detection of Hi in sterile sites. Typing of the isolates is performed at the National Reference Centre for meningococci and Haemophilus influenzae (NRCMHi) that has all permissions to access the samples and the data. Full typing of isolates including whole genome sequencing (WGS) was performed as previously described . MultiloHaemophilus influenzae b IgG ELISA).The anti PRP IgG were determined using the Kit according to the instruction of the supplier . ELISA titres were compared using the Medians values in the different subgroups and the percentages of subjects achieving the threshold of 0.15 μg/mL and 1 μg/mL. Geometric means of IgG concentrations as well as lower and upper 95% confidence intervals were also calculated for cases of vaccine failure. Data were analysed using the Chi-squared test and Mann-Whitney test was used for nonparametric test. A n = 501) of invasive isolates of Hi is depicted in Fig. n = 20; 4%), serotype b , serotype c ; serotype d , serotype e  and serotype f . The majority of the isolates  were non-typeable. The number of cases due to serotype b isolates increased to reach 25 cases in 2019 with a total number of 56 Hib invasive isolates during this 3-years period. Most of these Hib isolates  were among children under 5 years of age  among children under 5 years old during the 2017–2019 period. However, Hif and non-typeable invasive isolates were more frequently observed among subjects of 5 years of age and older n = 29 out of 49 (59.2%) and n = 302 out of 365 (82.7%) respectively. Whole genome sequence (WGS) data were available for 55 of the 56 Hib isolates (98.2%) and showed that most of these isolates belonged to the ST-6 (n = 32) and 21 other isolates differed by 1, 2 or three loci from ST-6  and proportion (66.1%) of Hib cases among children under 5 years of age during the period 2017–2019 was unexpected. We checked the vaccination status of Hib cases. There were 24 children who were vaccinated completely (n = 9) or partially (n = 15 with one or two doses) while the remaining 13 did not receive any dose. There was no geographical clustering of vaccine failure cases. The clinical presentations were mainly meningitis (n = 16) followed by bacteraemia (n = 7) and one case of epiglottitis. All the 24 vaccinated cases were vaccinated according to the new schedule 2 + 1 that was implemented in 2013 in France. They were non premature with no known immunodeficiency. These cases were distributed during this period as 2 cases in 2017 and 11 cases in each 2018 and 2019. We next explored the levels of anti-PRP IgG among the completely vaccinated children and obtained sera at the admission from the 6 corresponding vaccine failures with a complete 2 + 1 scheme.The high number (P = 0.01), indicated a significant secondary immune response 1 month post infection. All these data suggest that the vaccine failures are most likely due to decline of IgG titres after the third dose at the age of 11 months.The levels of anti-PRP IgG were lower than 1 μg/ml among all the 6 vaccine failure cases (complete 2 + 1 scheme) with median and geometric mean of anti-PRP IgG concentration of 0.43 μg/ml and 0.40 μg/ml (95% CI 0.16–0.98) Respectively  was composed of children borne before 2013 and named “3 + 1 group” as this schedule was used before 2013. The second group (n = 102) contained the children borne since 2013 and corresponded to the “2 + 1 group”. Each group was further divided into 6 subgroups according to age at the time of sampling: < 6 months, 6–11 months, 1 year, 2 years, 3 years and 4 years of age   were also lower for the 2 + 1 group compared to those of the 3 + 1 group. This was also observed when the threshold was 1 μg/ml of anti-PRP IgG (the putative threshold for long-term protection from invasive Hib disease) and particularly for children of 2 years of age (56% versus 25%)  of anti-PRP IgG are used to correlate anti-PRP IgG with protection against Hib disease. These thresholds were reported to be correlated with short and long term protections respectively . HoweverMeasuring antibody avidity and the isotype of these antibodies can also add to the understanding of these cases and to refine the hypothesis .The simplification of anti-Hib vaccination in France in 2013 to a 2 + 1 scheme seems to be associated with lower levels of anti PRP IgG. Hib antibodies also wane rapidly after the 11 months booster and may not be enough to ensure long term protection. Seroprevalence studies as performed in this work are required to inform the decision making in choosing vaccination polices.


OMHPs) is essential for their use in optoelectronic applications. Moreover, increasing the emission intensity, particularly for blue emission, is considerably a challenge. Here, intriguing pressure‐induced emission (PIE) is successfully achieved from an initially nonluminous 0D OMHP [(C6H11NH3)4BiBr6]Br·CH3CN (4BiBr7Cy) upon compression. The emission intensity increases significantly, even reaching high‐efficiency blue luminescence, as the external pressure is increased to 4.9 GPa. Analyses of the in situ high‐pressure experiments and first‐principle calculations indicate that the observed PIE can be attributed to the enhanced exciton binding energy associated with [BiBr6]3– octahedron distortion under pressure. This study of 4BiBr7Cy sheds light on the relationship between the structure and optical properties of OMHPs. The results may improve potential applications of such materials in the fields of pressure sensing and trademark security.Understanding the structure–property relationships in Zero‐dimensional (0D) organic–inorganic metal halide perovskites ( 6H11NH3)4BiBr6]Br·CH3CN (4BiBr7Cy). This research provides a new research approach for the acquisition of the high efficiency blue emitting materials.The deformation of bismuth bromide octahedra stimulated by lattice shrinkage enhances exciton–phonon coupling, resulting in bright blue emission at pressure of 4.9 GPa or low temperature for the Zero‐dimensional (0D) organic–inorganic metal halide perovskite [(C For Zero‐dimensional (0D) OMHPs, individual metal halide octahedral anions are completely surrounded and isolated by organic cations. Because of the strong spatial confinement of isolated metal halides, the emissions of 0D OMHPs feature broadband spectra, large Stokes shifts, and high photoluminescence (PL) quantum efficiencies. These remarkable features make them excellent candidates for use as solid‐state phosphors. Therefore, the recent studies have favored 0D OMHPs. However, a large Stokes shift is the main reason for the lack of blue luminescence in 0D OMHPs. Thus, developing an effective strategy to achieve high‐efficiency blue luminescence with 0D OMHPs remains a pressing challenge.Organic–inorganic metal halide perovskites . In particular, Zhang et al. found that when (C6H5C2H4NH3)2PbBr4 was subjected to enhanced pressure, the blue emission of the free‐exciton state weakened or disappeared, and the red emission of the self‐trapping exciton state appeared or increased. Therefore, overcoming large structural distortion under pressure is a considerable challenge.Pressure, as an independent thermodynamic parameter, has been the focus of achieving efficient blue luminescence for 0D tructure.5 ReceOMHPs. It has been reported that heavy ns2 electron structure atoms (such as lead and bismuth) cause a small Stokes shift due to the strong spin–orbit coupling perturbations in metal halide crystals. However, the use of lead ions may restrict large‐scale manufacturing due to its toxicity and possible bioaccumulation. Bi3+ has the same 6S26P0 electronic structure as Pb2+ and a similar ionic radius, and Bi‐based halide perovskites exhibit lower toxicity and better chemical stability than lead. Thus, Bi3+ is an excellent candidate for use in lead‐free low‐toxicity perovskite materials. In addition, rigidifying the chemical environment around metal halide anions in crystals is also an efficient method for reducing the Stokes shift of 0D organic–inorganic hybrid materials.Consequently, decreasing the Stokes shift is the key to achieving blue luminescence for 0D crystals.8 HoweOMHPs [(C6H11NH3)4BiBr6]Br·CH3CN (4BiBr7Cy). The organic cation C6H11NH3+ confines the bismuth bromide octahedron in a relatively rigid hydrogen bond network. 4BiBr7Cy exhibits an unexpected pressure‐induced emission (PIE) at room temperature (RT) when the intrinsically nonemitting crystals are compressed to 4.9 GPa. The pressure‐dependent absorption spectra, angle‐dispersive synchrotron X‐ray diffraction (ADXRD) patterns, and Raman spectra combined with temperature‐dependent emissions and single‐crystal X‐ray diffraction (SCXRD) results, and theoretical calculations indicate that the attracting blue emission resulted from the exciton transitions with the enhanced exciton binding energy that are triggered by the minor distortion of the [BiBr6]3– octahedron under pressure. The results demonstrate that lead‐free metal halides are promising for high‐efficiency blue luminescence and that pressure‐controlled emission can overcome the limits of conventional synthetic chemistry.Herein, we perform a systematic high‐pressure study of a 0D 24BiBr7Cy was determined by SCXRD . As depicted in Figure 3+ cation occupies the center of the octahedron, and six bromide ions are located at the vertices. The [BiBr6]3– octahedra are periodically embedded in the crystal lattice together with the organic cations C6H11NH3+ to from bulk materials, thus creating an 0D OMHP structure at the molecular level. Hydrogen bond interactions among the various components are not neglected in 4BiBr7Cy . As shown in Figure 6]3– octahedra connect to the surrounding organic cation C6H11NH3+ through strong N‐H···Br hydrogen bonds. Acetonitrile molecules are also linked by hydrogen bonds with the [BiBr6]3– octahedron . The purity of Cy4BiBr7 was confirmed by the well‐overlapped powder X‐ray diffraction (PXRD) patterns between the as‐synthesized samples and the simulated single‐crystal data .The precise structure of4BiBr7Cy initially did not exhibit a PL response to external pressure and showed bright blue emission as the pressure increased. As shown in Figure 4BiBr7Cy exhibits an apparent enhancement. Note that the corresponding PL intensity shows a remarkable increase with increasing pressure, eventually reaching a maximum at a pressure of 4.9 GPa. Upon further compression, the PL intensity gradually decreased and was reached when the pressure approached 13.0 GPa. This interesting PIE phenomenon can also be demonstrated from the changes in the PL photograph under laser irradiation at 355 nm. It is obvious that when the pressure increases to a certain value, the pressure‐dependent PL photographs clearly turn bright, as shown in Figure 4BiBr7Cy crystals also gradually display blue PL as the temperature decreases under ambient conditions .Unexpectedly, s Figure . This bl4BiBr7Cy upon compression are shown in Figure 4BiBr7Cy crystals are colorless under ambient light and ambient conditions and have an absorption edge located at ≈400 nm . It is found that the absorption spectra of Cy4BiBr7 are greatly stable up to 13.0 GPa. With the increase in external pressure, the absorption spectra underwent a successive redshift, indicating the band gap narrowing of 4BiBr7Cy with the pressure changes. This band gap engineering as a function of pressure should be highly related to the octahedral motif changes with increasing pressure.The absorption spectra of in situ high‐pressure ADXRD up to ≈20.13 GPa. The evolutionary information for the structure of 4BiBr7Cy upon compression is shown in Figure θ = 2.6° corresponding to the Bragg (001) reflection, and the others have labeled shown in Figure S8, Supporting Information. As the pressure increased, all Bragg diffraction peaks monotonically shifted toward higher diffraction angles, which resulted from the pressure‐induced lattice contraction. Moreover, no new peaks appeared upon compression, indicating that 4BiBr7Cy did not experience any structural phase transition. And ADXRD results analysis also revealed that4BiBr7Cy possesses the same space symmetry at ambient conditions and 20.13 GPa  was associated with the [BiBr6]3– octahedra, and this movement originated from the distortion of the [BiBr6]3– octahedron . As the pressure increased, the vibrational mode of Alg in [BiBr6]3– octahedra showed a normal movement in the direction of a high Raman shift, which was attributed to the reduction of interatomic distance. As the progressive deteriorated crystallinity under higher pressure, the vibrational intensity of A1g mode weakened until disappeared. The peak around 1334.71 cm–1 at ambient pressure can be attributed to the vibration modes of C6H11NH3+ cation. With increasing pressure, the vibrational modes of C6H11– show a monotonic blue‐shift. However, the vibrational modes of –NH3+ hardly shifted with pressure . We speculate that this was due to the pressure‐induced lattice shrinkage limiting the atomic vibration and concurrently increasing the interreaction between the C6H11NH3+ cation and the [BiBr6]3– anion. It was worthy to note that the ADXRD and Raman peaks returned to the initial positions upon the complete release of pressure, indicating the pressure‐dependent reversibility of4BiBr7Cy.To investigate the relationship between the optical properties and structural evolution upon compression, we performed a Figure . The Ramrmation).13 As 6H11NH3+ cation changes, as shown in Figure  Both blue‐shifts and red‐shifts were observed in characteristic modes . The volume of the lattice underwent considerable shrinkage, leading to strenuous repulsion between the [BiBr6]3– octahedron and the electron waves on the H atoms in the cyclohexyl group. Hence, the frequency of C—H stretching in C6H11– increased. However, both the N—H stretching and bending modes in the NH3+ experienced red‐shift as pressure increased. This reverse change trend for N—H modes relative to the C—H and C—N modes can be attributed to the cationic charge on NH3+. The pressure‐induced lattice shrinkage further enhanced the electrostatic attraction between the cationic charge in NH3+ and their neighboring anionic charge on the [BiBr6]3– anion.To further investigate the behavior of the organic and its interplay with the inorganic moiety, we carried out high‐pressure infrared absorption spectrum (IR) experiments at RT to provide information about the C4BiBr7Cy at different pressures . The variations in cell parameters and cell volume of 4BiBr7Cy upon compression are displayed in Figure 4BiBr7Cy were greatly reduced below 5.0 GPa. Above 5.0 GPa, the rate of reduction slows down. Notably, cell parameters and cell volume of4BiBr7Cy were continuously compressed without collapses, which confirmed that 4BiBr7Cy did not undergo phase transition within the detection pressure range. More importantly, such structural evolutions correspond to the trend in the experimental measurements of emission enhancement.Rietveld refinements of the ADXRD patterns can obtain the unit cell parameters ofPIE of 4BiBr7Cy and the lattice shrinkage. Moreover, the low‐temperature SCXRD data under ambient conditions verified that lattice shrinkage induced the blue emission of 4BiBr7Cy . As shown in Figure 6]3– octahedron changed with shrinkage of the lattice. The larger values of ∆d (Bi—Br bond length distortion) and δ2  at low temperatures than RT intuitively reflected this change (see Supporting Information for details). We found that the bismuth bromide octahedron in 4BiBr7Cy has a lesser structural distortion than other 0D OMHPs . This may be used to explain the small Stokes shift blue emission of 4BiBr7Cy at low temperature or high pressure. It should be noted that there was also no phase change between low temperatures and RT . In metal halide perovskites, the distortion of the metal halide octahedron can improve exciton–phonon coupling, thereby activating PL. Thus, the abovementioned PIE of 4BiBr7Cy at RT should originate from the slight distortion of the [BiBr6]3– octahedron upon compression.Through the above analysis, we can guess that there was relevance between the 4BiBr7Cy. The [BiBr6]3– octahedra were separated to form 0D structure  mainly encompassed the d orbitals of Bi and p orbitals of Br, and the conduction band minimum (CBM) was contributed by the d orbitals of Bi and p orbitals of the two Br atoms in each [BiBr6]3– octahedron  calculations were performed to investigate the structural, electronic, and spectral properties of e Figure  that coue Figure . This ann Figure . Upon con Figure . Anothere Figure .PIE of 4BiBr7Cy. Incident photons are absorbed by promoting electrons from the GS into higher energy excited states, including the FC state and FE state (Figure Based on the above results, we propose that the changes in the electronic properties are responsible for the e Figure . Under ae Figure .34BiBr7Cy crystal with a lead‐free 0D OMHP structure. Notably, by applying mild pressures, we were able to make originally nonluminescent crystals emit a bright blue color. Specifically, the pressure deformed the bismuth bromide octahedron, resulting in enhanced electron–phonon coupling. In situ high‐pressure ADXRD and Raman spectra, as well as the DFT results, further corroborate this PIE mechanism. Furthermore, the variable‐temperature SCXRD analysis supported this finding. Our work verifies the possibility of PL engineering in 0D lead‐free OMHPs with enhanced functionality through high‐pressure structural modulation. Additionally, our study provides a new avenue for exploiting high‐efficiency blue luminescence materials.In conclusion, we have designed and synthesized a The authors declare no conflict of interest.Supporting InformationClick here for additional data file.


The method allowed to determine the Collision Cross Sections (CCSs), which were used to assess the size changes experienced by the host upon encapsulation of the guest molecules. When fullerenes were used as guests, the host is expanded ΔCCS 13 Å2 and 23 Å2, for C60 or C70, respectively. The metallorectangle [1]4+ was also used for the encapsulation of a series of polycyclic aromatic hydrocarbons (PAHs) and naphthalenetetracarboxylic diimide (NTCDI), to form complexes of formula [(NTCDI)2(PAH)@1]4+. For these host:guest adducts, the ESI IM‐MS studies revealed that [1]4+ is expanded by 47–49 Å2.. The energy‐minimized structures of [1]4+, [C60@1]4+, [C70@1]4+, [(NTCDI)2(corannulene)@1]4+ in the gas phase were obtained by DFT calculations.IntroductionThe encapsulation of the tetracationic palladium metallosquare with four pyrene‐bis‐imidazolylidene ligands [ We present an ion‐mobility mass spectrometry (IM‐MS) study on the encapsulation characteristics of a shape‐adaptable organometallic metallocage, and demonstrate that IM‐MS in combination with DFT calculations constitutes a reliable approach to quantify distortions experienced by the host upon guest encapsulation. Described by Koshland in 1958,Ion mobility MS separates gas‐phase ions  by allowing them to drift under the influence of an electric field against a buffer gas. The drift times measured in IM‐MS depend on the ion collision cross sections (CCS) and can be ultimately correlated to ion size and shape. Examples of the use of the IM‐MS technique have been reported for supramolecular coordination complexes (SCCs) supported by N‐, O‐ donor, Werner‐type ligands, and include topological characterization studies1](BF4)4 in Scheme 60 or C70).1]4+ was then used for the encapsulation of series of three‐stacked heteroguests,1](BF4)4 upon the encapsulation of fullerenes (C60 and C70), and three‐stacked planar heteroguests. We consider that the shape adaptability, robustness, solubility in ESI‐compatible solvents and its intrinsic 4+ charge, make [1](BF4)4 an optimum candidate for investigating its guest‐induced distortions by ESI IM‐MS.Supramolecular organometallic complexes (SOCs)1](BF4)4 in acetonitrile shows the base peak at m/z 766.4, assigned to [1]4+. A lower intensity peak at m/z 1050.6 due to [1 + BF4]3+ is also observed. Lower nuclearity species were not detected neither as a result of gas‐phase fragmentation of [1]4+ upon ESI, nor via its degradation in solution when the ESI mass spectrum was recorded after several days. This observation indicates that [1]4+ is stable at the μM‐concentrations used in the ESI experiment. The ESI IM mass spectrum of [1]4+ (see SI) is identical to that found by single‐stage ESI‐MS. The experimental isotopic pattern of [1]4+ perfectly matches the simulation, thus the presence of isobaric [Pd2L2]2+ or [Pd3L3]3+ species formed by heating or fragmentation upon IM conditions can be discarded.The ESI mass spectrum of 1 μM solutions of [60 or C70) could be readily performed by sonication of [1](BF4)4 and the corresponding fullerene to yield [C60@1](BF4)4 and [C70@1](BF4)4.60@1]4+ (m/z 946.4) and [C70@1]4+ (m/z 976.4) together with that of [1]4+ (m/z 766.4) are shown in Figure As we showed previously, the encapsulation of fullerenes (Cation of (BF4)4 an1]4+ and the fullerene adducts, indicate that the [fullerene@1]4+ complexes are truly capsular assemblies in the gas‐phase, and that [1]4+ and [fullerene@1]4+ share similar topology. Nevertheless, a small increase in the drift time (tD) is observed upon fullerene encapsulation  < [C60@1]4+ (720 Å2) < [C70@1]4+ (730 Å2).4− revealed a similar trend as that found for the quadruply‐charged analogues  stacks (see Scheme 2(PAH)@1]4+ complexes  were formed by the direct mixing of the components. Herein, we also performed experiments using phenanthrene, anthracene, perylene and corannulene, to widen the scope of the study. Complexation‐induced 1H chemical shift changes were observed in the NMR spectra, consistent with the encapsulation occurring in solution . In all cases, the ESI mass spectra displayed prominent supramolecular peaks assigned to [(NTCDI)2(PAH)@1]4+. However, switching to the IM‐MS mode resulted in a dramatic reduction of the peak abundances of these supramolecular aggregates, which became barely detectable, in most cases. This observation is strongly suggestive of a labile nature of the [(NTCDI)2(PAH)@1]4+ complexes, compared to those of the fullerenes, for which both single‐stage and ESI IM mass spectra were identical. Similar conclusions can be drawn from gas‐phase fragmentation studies of the isolated [(NTCDI)2(PAH)@1]4+ and [(fullerene)@1]4+ ions by collision‐induced dissociation (CID) experiments. The fullerene‐encapsulated ions [(fullerene)@1]4+ remained largely unchanged under CID conditions. Conversely, the series of [(NTCDI)2(PAH)@1]4+ cages dissociated similarly and produced characteristic fragment ions due to eliminations of the guests under identical conditions . Energy resolved CID experiments (see breakdown graphs in SI) indicate that guest eliminations occur simultaneously.We showed recently that metallosquare 4+ is eff2(PAH)@1]4+ aggregates below their dissociation threshold. Figure 2(PAH)@1]4+ assemblies, exemplified for the case of [(NTCDI)2(triphenylene)@1]4+.Fragmentation or isomerization of fragile molecules due to heating within the TWIM‐MS drift tube is a well‐documented phenomenon.2(PAH)@1]4+ cationic assemblies was studied by ESI IM‐MS. Again, a common feature inferred from the ion mobility ATDs shown in Figure 2 range. These similarities indicate that the π‐donor PAH guests, while sandwiched between the two π‐acceptor NTCDI molecules, are embedded within the cavity of [1]4+ and show overall similar dimensions of the supramolecular assembly.Under the optimized conditions, the whole series of quaternary [(NTCDI)1]4+, the 1H NMR spectrum displayed broad signals, which indicated labile encapsulation . However, ESI‐IM‐MS provided convincing evidence that the host‐guest [(NTCDI)2(corannulene)@1]4+ was formed, and its composition and topology could be assessed by comparing with the series of planar π‐donors. Although the incorporation of this curved PAH could be expected to expand the volume of the metallosquare host, the observed CCS value of 746 Å2 was practically identical to the values obtained for the other [(NTCDI)2(PAH)@1]4+ species in Figure The complexation of corannulene is singular because its bowl‐shaped nature renders a less effective interaction with planar polyaromatic donors, such as NTCDI.1]4+ with the whole series of encapsulated guests, we performed DFT (MN15‐L/Def2SVP) calculations of [1]4+, [C60@1]4+ and [C70@1]4+ in gas phase. Due to its intriguing nature, we also calculated the structure of [(NTCDI)2(corannulene)@1]4+. To simplify the calculations and to avoid considering a large number of conformational isomers, we substituted the nBu groups bound to the nitrogen atoms of the imidazolylidenes by methyl groups. Figure 1′]4+ denotes the modified host, possessing all NMe groups.In order to attain an accurate picture of the distortions suffered by [1′]4+ in the gas phase displays a distorted arrangement from an ideal square. Shrinkage from opposite corners of the square leads to a rhombohedral‐shaped molecule 4, which showed an almost perfect square‐shaped geometry for [1]4+. The difference can be ascribed mainly to the presence of three molecules of solvent (DMF) and three counter‐anions (BF4−) in the interior of the cavity of the supramolecular host in the solid‐state structure, which are obviously absent in the gas‐phase cation. The encapsulation of C60 and C70 does not leave room within the cavity for compression and consequently, the gas‐phase structures are rather similar to those found in the solid‐state, although both show a rhombohedral shape. For the case of [C70@1′]4+, the C70 molecule displays its longer axis parallel to the C2 axis of the molecule, therefore minimizing the steric congestion in the cage. The structure of [(NTCDI)2(corannulene)@1′]4+ shows that the corannulene guest is sandwiched between the two NTCDI molecules. The latter are significantly bent, most likely for maximizing the π‐stacking interaction with the bowl‐shaped guest. Interestingly, the centroid of the corannulene molecule is off the axis defined by the centroids of the opposite pyrene moieties of the cage, which also contain the centroids of the NTCDI guests 2(corannulene)@1′]4+ were calculated using Trajectory Methods (TM), implemented in the IMoS software.1′]4+ cation and its respective host:guest adducts display predicted CCS values 2(corannulene)@1′]4+) that are consistently smaller than the experimental ones. This is a consequence of the use of the small NMe instead of NBu groups in the calculated structures. The structural differences are linearly correlated as illustrated in Figure The DFT‐optimized structures were used as inputs for CCS predictions, and then these were compared with the experimental data obtained by IM‐MS. The CCS values for [1]4+, which is able to expand by ΔCCS 37–39 Å2 from its empty form to accommodate the three guests in [(NTCDI)2(PAH)@1]4+. Equally interesting is the evidence that ESI IM‐MS may also be useful for detecting distortions experienced by guests upon encapsulation, as we showed for the case of the flattening of corannulene. This result is remarkable, especially if we take into account that the flattening of corannulene upon encapsulation inside a molecular host has been observed experimentally very few times,[1]4+ constitutes an excellent prototype for this type of studies, due to the high stability conferred by the di‐NHC linkers, the large binding affinities with three‐ and two‐dimensional hosts, and the intrinsic 4+ charge of all the resulting host‐guest complexes. We expect that this study will inspire researchers in the field of supramolecular organometallic chemistry to incorporate the use of the IM‐MS technique to facilitate the study of structural properties such as breathable motions or guest‐induced distortions of the metallosupramolecular assemblies.Our results demonstrate that IM‐MS in combination with DFT modeling and CCS predictions is a reliable tool for assessing guest‐induced host distortions on the basis of their CCS values. The CCS data also serve to illuminate the exceptional size adaptability of [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.


To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps.Antibodies to the SARS‐CoV‐2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2‐blocking antibodies (ACE2‐blocking Abs), antibodies to the receptor‐binding domain (RBD) of  variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort.p < .0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2 compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the hemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6%–90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo interferon (IFN)γ ELISpot responses above the positive threshold. The ACE2‐blocking antibodies  and ex vivo IFNγ responses  at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose.All individuals (100%) had SARS‐CoV‐2‐specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2‐blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2‐blocking Abs  had higher antibody and T cell responses, 6 months post first dose of the AZD1222 vaccine, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose. However, after it was rolled out to the public, due to the delay in obtaining the second dose, most individuals received their second dose 20 weeks after obtaining their first dose. We showed that at ≥16 weeks postimmunization with a single dose of AZD1222, 93.7% of those >70 years had SARS‐CoV‐2‐specific antibodies, although ACE2 receptor‐blocking antibodies  was significantly less in those >60 years of age.Currently, many studies have shown that there is waning of immunity with many of the COVID‐19 vaccines following the second dose.2n = 88) in the community (cohort 2), who received their first dose between February 15 to March 4, 2021 and the second dose between June 1 to August 4, 2021 were included in the study 6 weeks after their second dose . Enrolling both cohorts 12 weeks post second dose was difficult due to the planned rollout of booster doses in Sri Lanka since October 2021.Three hundred and thirty‐six health care workers (HCWs) (cohort 1) who received their first dose of AZD1222/Covishield vaccine between January 29 to  February 5, 2021 and their second dose between  April 23 to May 5 were included in the study  3 months after receiving the second dose of the vaccine (6 months after the first dose). To compare the influence of the gap between the two doses on the immunogenicity of the vaccine, another cohort of individuals  were detected by using the Wantai SARS‐CoV‐2 Ab ELISA , which detects antibodies to the receptor‐binding domain (RBD) of the spike protein. The assay was carried out according to the manufacturer's instructions and the antibody index (an indirect measure of the antibody titer) was calculated by dividing the absorbance of each sample by the cutoff value, according to the manufacturer's instructions.2.2The surrogate virus neutralization test (sVNT), which has been shown to correlate with the presence of neutralizing antibodies was used to measure ACE2R‐Abs as previously described according to the manufacturer's instructions (Genscript Biotech).2.3The HAT was carried out as previously described using the B.1.1.7 (N501Y), B.1.351 , and B.1.617.2 versions of the IH4‐RBD reagents,2.4Qualitative detection of antibodies to SARS‐CoV‐2 nucleocapsid (N) antigen in human serum was performed using Elecsys® Anti‐SARS‐CoV‐2 electrochemiluminescence immunoassay  in Cobas e 411 analyzer (Roche Diagnostics). A cutoff index (COI) ≥ 1.0 was interpreted as reactive and COI < 1.00 was considered nonreactive as per the kit guidelines.2.52. The cells were removed, and the plates developed with a second biotinylated antibody to human IFNγ and washed a further six times. The plates were developed with streptavidin‐alkaline phosphatase (Mabtech AB) and colorimetric substrate, the spots were enumerated using an automated ELISpot reader (AID Germany). Background  was subtracted and data were expressed as the number of spot‐forming units (SFU) per 106 PBMCs. A positive response was defined as mean ± 2 SD of the background responses.Ex vivo IFNγ ELISpot assays were carried out using freshly isolated peripheral blood mononuclear cells (PBMC) obtained from 57 individuals. Individuals for T cell assays were recruited from those in whom these assays had been carried out at 1 month following the first dose of the vaccine.2.6χ2 Association tests were performed at a confidence level of 95% using the R software to identify the statistically significant associations of the age categories and the sex of the individuals with seropositivity. Kruskal–Wallis test was used to determine the differences between the levels of antibodies between different age groups. Spearman's correlation coefficient was used to determine the correlation between antibody, T cell responses, and the age of an individual.The 95% confidence intervals for seropositivity for each age category were calculated using the R software (version 4.0.3) and R‐studio (version 1.4.1106). Pearson 33.1n = 297). There was no significant difference (p = .79) between the antibody titers in the three different age groups  in this cohort 1 , all of the 336 (100%) of the HCWs (cohort 1) had SARS‐CoV‐2‐specific total antibodies . Antibodies to the N protein were tested in both cohorts (cohort 1 and cohort 2) to determine if they had been infected during the 6 months since obtaining the first dose and 39/336 (11.6%) were excluded from further analysis due to the presence of antibodies to the N protein. Therefore, further analysis was carried out in those who were not found to have the natural infection during this period   between the antibody titers in the three different age groups  in cohort 2. In both cohorts, there was no significant difference (p = .96–.99) in the seropositivity rates or the antibody levels (indicated by antibody indices) in those with comorbidities compared to those who did not have comorbidities.The second cohort was recruited at 6 weeks since receiving the second dose (6–7 months after the first dose) and the mean gap between the two doses in this cohort was 21.14 weeks (SD ± 1.95 weeks). Of this cohort, 11/88 (12.5%) had antibodies to the N protein and were considered as having been infected with the SARS‐CoV‐2 virus. All of the 77 individuals (100%) of this cohort (cohort 2) also had SARS‐CoV‐2‐specific total antibodies. There was no significant difference between the antibody titers in cohort 1 compared to cohort 2  Figure . As seen3.2n = 69) and cohort 2 (n = 70). In cohort 1 (those with a 12‐week gap between the two doses), 65/69 (94.2%) gave a positive result for the presence of ACE2‐blocking Abs, while 68/70 (97.1%) in cohort 2 gave a positive response. The positivity rates were found to be significantly different, higher in cohort 1 than cohort 2  and cohort 2 had significantly higher titers  compared to cohort 1    Figure  or cohor) Figure .3.3n = 69) and in cohort 2 (n = 70). These are the same individuals in whom ACE2 receptor‐blocking antibodies were measured. The proportion of individuals who gave a positive result for the WT and the VOCs is shown in Table p = .068), 40–59 years (p = .658), and the >60 year age group (p = .251) , and the VOCs B.1.1.7, B.1.351, and B.1.617.2 in cohort 1  Figure . The low) Figure .p = .006), B.1.1.7 (p = .04), B.1.351 (p = .0006), and B.1.617.2 (p = .0005) were significantly higher in those in cohort 1 compared to cohort 2  and in cohort 2 (n = 29). In cohort 1, the positive threshold was set at 110 SFU/1 million PBMCs and accordingly, 17/57 (29.8%) gave a positive response. In cohort 2, the threshold for a positive response was set at 272 SFU/1 million cells. Accordingly, 17/29 (58.6%) gave a positive response. The frequency of ex vivo IFNγ ELISpot responses were significantly higher for the S1 pool of overlapping peptides (p = .009) and the S2 pool of overlapping peptides (p = .0006) in cohort 2 compared to cohort 1  than for the S2 pool of overlapping peptides  in cohort 1. In cohort 2, although the responses to the S1 pool was higher  than those for S2 , this was not significant (p = .06).The responses to the S1 pool of overlapping peptides  were significantly higher (3.5p < .0001) , while there was no significant difference in those in the 20–39 age group and >60 age group, in the levels from 12 weeks post first vaccine and 12 weeks post second vaccine . In the >60 age group, although the levels at 12 weeks post second dose was significantly higher than that of 4 weeks post first dose (p = .049), the levels were still lower.The kinetics of antibodies and T cell responses could only be studied in cohort 1, as we had data at baseline, 4 weeks after the first dose, 12 weeks after the first dose, and 12 weeks after the second dose (6 months after the first dose) only for cohort 1. Only 171 individuals (N antibody negative) were included in the analysis for kinetics of the SARS‐CoV‐2 total antibodies as all four time points were available only in these individuals. Of the 171 individuals, 73 were in the 29–39 age group, 87 in the 40–59 age group, and 11 in the >60 age group. The SARS‐CoV‐2 total antibodies were significantly higher from the time from obtaining the second dose to 12 weeks later  Figure . Howevere Figure . In the p < .0001) at 12 weeks post second dose compared to 12 weeks post first dose , but not in the other two age groups. The antibodies to the RBD of the WT was also assessed over time in this cohort (n = 40), and there was no significant difference (p = .59) in the antibody titers to the RBD of the WT, assessed by the hemagglutination assay from 12 weeks post second dose compared to 12 weeks post first dose , in cohort 1 for all four time points. Using the Friedman test we found that the ACE2‐Ab levels were significantly higher  in responses 12 weeks post second dose compared to 12 weeks post first dose . While the ex vivo spike protein‐specific (overlapping peptide) responses increased with time, there was no significant difference . However, in further analysis, this correlation was only seen in the 20–39 age group , whereas no significant correlation was seen in other age groups. However, no such correlation was seen in the total antibodies at ≥16 weeks post first dose and 6 weeks post second dose in cohort 2 .In cohort 1, the antibody levels at 12 weeks post single dose significantly correlated with the SARS‐CoV‐2 total antibodies at 12 weeks post second dose  the ACE2‐blocking Abs at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose. A significant correlation was seen in cohort 2  as well in antibody levels at ≥16 weeks post first dose and 6 weeks post second dose. The ex vivo IFNγ ELISpot responses showed the strongest correlation in cohort 1 in 12 weeks post first dose and 12 weeks post second dose . Data were not available to carry out this analysis for cohort 2.In cohort 1 . In contrast, we showed that 12 weeks after the second dose of Sinopharm/BBIBP‐CorV, only 60.9% of individuals had ACE2‐blocking Abs, with median titers of 35.6%.In summary, we have investigated the immune responses following two dosing schedules of the AZD1222 in Sri Lankan individuals. We found that those who had a wider dosing gap had higher antibody and T cell responses, 6 months post first dose of the vaccine when compared to those with a 12‐week dosing gap. It would be important to assess the significance of these differences in immune responses based on the dosing gap on vaccine efficacy.Supporting information.Click here for additional data file.


Cases in which cations, anions, or both are incorporated into the final products are also included. The purpose of this Review is to raise caution about the chemical reactivity of ionic liquids and deep eutectic solvents and to establish a guide for their proper use.Ionic liquids and deep eutectic solvents are of growing interest as solvents for the resource‐efficient synthesis of inorganic materials. This Review covers chemical reactions of various deep eutectic solvents and types of ionic liquids, including metal‐containing ionic liquids, [BF The chemical reactivity of ionic liquids and deep eutectic solvents can intentionally be exploited as a synthetic tool to prepare inorganic materials that are difficult or even impossible to obtain by traditional synthetic routes. This Review summarizes recent developments in inorganic syntheses that take advantage of reactions with ionic liquids or deep eutectic solvents. For example, ILs can facilitate the dissolution of versatile precursors, including both inorganic and organic compounds, which is fundamental for the synthesis of most materials.15, 16In 2003, the concept “deep eutectic solvent” was first coined by Abbott et al.Tonset) derived from the ramped temperature in thermogravimetric analysis.[The thermal and chemical stabilities of ILs are usually highlighted as advantageous for inorganic synthesis. Previous investigations have indicated that the actual degradation temperature of ILs is overestimated by the onset decomposition temperature Tonset der2]− anions could be used as the flux medium for the direct recycling of spent cathode materials or as effective structure‐directing templates for the synthesis of advanced catalysts and anode materials because of their good thermal and chemical stability.[2]−‐containing imidazolium ILs can be readily reused and recycled after the reaction, thus providing new strategies for designing sustainable ILs for advanced inorganic synthesis.ILs are readily accessible as inert reaction media for inorganic synthesis. Dai and co‐workers demonstrated that several imidazolium ILs containing 2[CuCl4] under solvothermal conditions.Dai and co‐workers reported that hierarchical ZnO structures with diverse morphologies were obtained under an ionothermal synthesis when employing the Zn‐containing IL Zn(L)2[Cu2Cl6] by a solvothermal method.+ prefers to adsorb onto the (001) facets of CuS. On the other hand, the assembly of CuS microspheres is influenced by the alkyl chain of the Cu‐IL. A tight hierarchical CuS structure is the preferred form when a short‐chain IL is used. ZnS quantum dots were prepared using the Zn‐containing IL [CnMIm][ZnCl3]  as a precursor, template, and solvent.2 microspheres wrapped by N‐doped reduced graphene oxide were synthesized from the Fe‐based IL [C12MMIm][ FeCl4].Zheng and co‐workers demonstrated that three‐dimensional (3D) hierarchical CuS microspheres assembled from nanosheets were produced from the Cu‐containing IL precursor [BMIm]ning IL CnMIm− or [PF6]−) ILs can be used as fluorine sources, thereby opening a safe pathway to prepare metal fluorides with novel morphologies and functions. The hydrolysis of the [BF4]− anion occurs in the presence of a small amount of residual water in the IL or the water of crystallization in metal salts upon heating, thereby forming BF3⋅H2O and F−. The reaction of fluoride ions with metal ions under the given conditions contributes to the in situ crystallization of metal fluorides.6]− may also decompose to release F− under specific conditions.Inorganic metal fluorides are well‐studied for their applications in photonics, catalysis, biosensing, lubricants, electrochemical energy storage, and high‐temperature superconductor devices.66, 672 by using Mn(CH3COO)2⋅4 H2O as a manganese source and [BMIm][BF4] as a fluorine source 3⋅9 H2O and [BMIm][BF4] as the precursors  with particle sizes of a few tens of nanometers  display superior upconversion properties.Rare‐earth fluorides are an interesting family of compounds because of their optical properties, and their syntheses in ILs have been widely investigated. Yan and co‐workers reported that novel spherical NaYF5:Ce,Tb,Eu(Sm) sub‐microspheres with tunable sizes and morphologies could be synthesized from IL/ethylene glycol dual‐solvent systems  could be obtained by the microwave‐induced decomposition of their metal amidinate complexes [M{MeC(N(iPr)2)}n] (M(amd)n; M=MnII, FeII, CoII, PrIII, GdIII, ErIII) and triseuropium(III) (Eu(dpm)3) in [BMIm][BF4].[n and Eu(dpm)3 are suspended in dried [BMIm][BF4] under argon. An increased temperature drives the decomposition of M(amd)n/Eu(dpm)3 to release the metal species and the hydrolysis/decomposition of the [BF4]− anion to release F−. The reaction of metal species with F− results in the formation of metal fluorides.Janiak and co‐workers reported that a variety of transition‐metal and rare‐earth metal fluoride nanoparticles (MF4]− anions can be utilized in the presence of moisture or heat as a boron precursor in the reaction. Turbostratic boron nitride nanoflakes (t‐BN) were obtained on using [BMMIm][BF4] as the boron source.4] IL for the formation of the flake‐like t‐BN.Interestingly, it is found that the degraded components of  H5This section covers reactions of imidazolium or phosphonium salts with chalcogens  to generate the corresponding imidazole‐2‐chalcogenones or trialkylphosphane chalcogenides, respectively. The reaction mechanisms are also discussed. The utilization of chalcogenones or trialkylphosphane chalcogenides as chalcogen sources for the synthesis of metal chalcogenides is also summarized in this section.It has been recognized that the C2‐position of the 1,3‐dialkylimidazolium cation contains an acidic proton. Deprotonation of this position leads to the formation of a stable carbene, which is often used as an intermediate in organic synthesis.−, [HSO4]−, [SCN]−, [NTf2]−, and [BF4]−) imidazolium ILs were tested, no reactions with the chalcogens were observed. In these cases, ultrasound irradiation or strong bases are usually required. Ansell et al. demonstrated that [MMIm]I can readily react with elemental S to yield 1,3‐dimethylimidazole‐2‐thione in the presence of K2CO3 in methanol.2CO3” method has since been utilized to prepare a variety of chalcogenones, including 1,3‐dialkylimidazole‐2‐thione/selone, as a novel Se source.2(OCH3)]− ion) shows similar reactivity as the commonly used Na2SeO3 system. However, precipitates form in some systems from the reaction of Na2SeO3 with metal ions. The use of the [SeO2(OCH3)]− anion avoids this precipitation problem, because of its weaker polarizing capability, and the metal ions exist as free ions in the solutions. Moreover, particle growth is influenced by the adsorption of the [BMIm]+ cation on the formed crystal surfaces, leading to nanoparticles with diverse shapes. As a consequence of these distinct characteristics of this Se‐containing IL precursor, various metal selenides with special morphologies, including CuSe nanoflakes,x2−Se nanocrystals,2]− anion, and these were used as both the reaction media and Se reagents for the preparation of ZnSe nanoparticles under irradiation with microwaves at 220 or 250 °C.2+ ions leads to an interaction and the formation of an intramolecular coordinative Zn−Se bond. The decomposition of these NHC(Se)‐Zn complexes under microwave heating yields the corresponding ZnSe nanoparticles. Furthermore, the same group reported the synthesis of a variety of metal selenide  nanoparticles by decomposing the corresponding metal‐Se‐based molecular complexes in ILs.[SCN] can serve as both the solvent and sulfur source for the preparation of CdS nanocomposites.6ILs allow the creation of several types of open‐framework materials such as zeolites or metal‐organic frameworks (MOFs) as well as polyanionic/polycationic compounds. In many reactions, the IL cation or anion, as the counterion, is incorporated into the final structures as a result of the charge of the framework. In this section, reactions of ILs whose cations, anions, or both are incorporated into the final products are summarized.6.116MIm]Cl as the solvent, template, and chloride source.16MIm]+ cation with its long alkyl chain tends to adsorb on the (001) plane of BiOCl, and crystal growth along the c‐axis direction is inhibited, which leads to the formation of thin BiOCl nanoflakes. The obtained BiOCl nanoplates show potential applications for the removal of heavy metal ions in the field of wastewater treatment.As new types of halide sources, halide‐based ILs exhibit distinctive features compared to the commonly used halide sources. Zheng and co‐workers reported that various BiOCl nanostructures, such as ultrathin BiOCl nanoflakes, curved nanoplates, and nanoplate arrays, could be successfully prepared using [C4B7O12Cl can be obtained in [P66614]Cl in the presence of lithium acetate dehydrate and boric acid at a temperature of 200 °C for 48 h.4] tetrahedra and [BO3] triangles, forms interpenetrating channels, within which Li+ and Cl− are trapped —Sr2B5O9Cl nanorods, Sr2B5O9Br nanoneedles, and Ba2B5O9Cl nanosheets—were synthesized by the reaction of acetates A(OAc)2 and boric acid B(OH)3 in a mixture of [P66614]X and LiNTf2.4] tetrahedra and [BO3] triangles form the anionic [B5O9]3− framework with large channels. Halide anions, from the phosphonium halide ILs, and metal cations are trapped in these channels. Investigations further show that the reactivity of [P66614]X is promoted by adding the metal salt LiNTf2 to the reaction system, as it weakens the cation–anion interactions of the ILs. However, microcrystalline Pb2B5O9X , with an average diameter of 1 μm, was obtained in [P66614]X without adding LiNTf2.2+ and X− are incorporated into the channels of Pb2B5O9X compounds. These borate halides show efficient second harmonic generation, even as microcrystalline powders.Ruck and co‐workers investigated the ionothermal synthesis of several borate halide compounds using quaternary phosphonium halide ILs as both the solvent and halide source. The Li‐ion‐conductive polycrystalline Lid Figure . Similar6.24/2] and [AlO4/2]− tetrahedra linked through bridging oxygen atoms. Thus, the overall framework bears a negative charge caused by the negatively charged [AlO4/2]− units. A wide range of cations, such as Na+, K+, Ca2+, Mg2+, and others, can be accommodated in the zeolite cavities as counterions to balance the anionic charge. If a zeolite is prepared in an IL, the organic cations are incorporated into the zeolite channels to balance the charge and also act as structural templates.Zeolites are a family of porous materials that are widely applied in adsorption and catalysis.+ cations are present in the pores, balancing the negative framework charges as well as templating the formation of the zeolite structure.The first IL‐based synthesis of zeolites in ILs was reported by Morris and co‐workers in 2004.2PO4] (MIm=N‐methylimidazolium) for the ionothermal synthesis of crystalline metal phosphates .[2PO4] provides the phosphorus source to build the framework unit without phosphoric acid, as well as being a template and solvent. The obtained aluminum phosphate has a 2D structure with 8‐membered‐ring windows and the beryllium phosphate contains extra‐large 24‐membered‐ring channels. The [MIm]+ cations are located within the large channels in the case of beryllium phosphate or within the interlayer region in the case of aluminum phosphate.Since then, various framework types have been successfully obtained for aluminophosphates, including AEL,129 LTA,0.65Br0.35 for the first ionothermal synthesis of siliceous zeolites.4F within the pentasil units. The [BMIm]+ cations are incorporated inside the pores to balance the negative charge of the fluoride.Despite much success in the ionothermal synthesis of aluminophosphates, the application of ILs in the preparation of silica‐based zeolites still faces a major obstacle because silica is poorly soluble in ILs. Morris and co‐workers designed a task‐specific IL [BMIm]OH2]) used for the fabrication of porous transition‐metal oxides can be easily extracted and removed by organic solvents. Based on this [BMIm][NTf2] templating method, well‐defined nanoporous TiNb2O7 and mesoporous MnCeOx have been synthesized that exhibit superior performance for fast‐rechargeable lithium‐ion batteries and high activity for the selective oxidation of hydrocarbons at low temperature (100–120 °C), respectively.The IL‐templating effects were also used by Dai and co‐workers to synthesize porous transition‐metal oxides.30, 316.3MOFs, as a group of porous crystalline materials consisting of metal ions (clusters) coordinated to organic ligands, have received much research interest in many applications  because of their diverse structures, high porosity, and controllable chemical structures.3)2⋅4 H2O with H3btc using [EMIm]Br as a reaction medium. The framework is composed of Cd2 units with six btc ligands coordinated to each Cd2 moiety, while each btc is linked by three Cd2 units. This leads to the formation of an anionic [Cd(btc)]− framework. The [EMIm]+ cations are located in the void space of the framework.3btc is reacted with other metal precursors (e.g. Mn(OAc)2⋅4 H2O, Ni(OAc)2⋅4 H2O, or Co(OAc)2⋅4 H2O) in [CnMIm]X  the corresponding anionic frameworks ([Mn(btc)]−, [Ni3(btc)2(OAc)2]2−, or [Co3(btc)2(OAc)2]2−) are obtained, with 1‐alkyl‐3‐methylimidazolium cations within the channels.[BF4], [Cd3F(ina)32(4‐pic)2][BF4]2⋅⋅2 H2O, and [Cd3F(ina)33][BF4]2⋅⋅2 H2O  were prepared in [BMIm][BF4].4]− anion serves as a charge‐balancing unit located in the voids of the frameworks. However, the F− ions formed by in situ hydrolysis of the [BF4]− anion are trapped within the MOF framework through the formation of a [Cd3F]5+ unit. Thus, the [BMIm][BF4] IL serves as solvent, fluoride source, and structure‐directing agent.The anions of an IL can also be incorporated in the voids of the MOF as charge‐compensating species. Huang and co‐workers reported that three Cd2(btc)(OH)Br] in [PMIm]Br and [BMIm][Zn2(btc)(OH)I] in [BMIm]I by using Zn(NO3)2⋅6 H2O and H3btc as starting materials., through an ionothermal synthesis using a mixture of [DMPyr]Br and [BMPyr][OTf] 3][Ge4Se10] with SnCl4⋅5 H2O in tetrafluoridoborate ILs  in the presence of DMMP .x36−Gex24+Se132]24− (x=0 or 3.5) with an outer diameter of 2.83 nm and an inner diameter of 1.16 nm. The IL cations [BMMIm]+ and [BMIm]+ serve as counterions that surround the anions and partially penetrate them. This research further shows that the addition of a small amount of an amine promotes phase formation and phase selectivity of the products.In another case reported by Dehnen and co‐workers, two polyanionic compounds [BMMIm]3).Polycationic compounds are commonly carried out in Lewis‐acidic ILs, which usually combine alkylimidazolium halides with more than equimolar amounts of aluminum or gallium trihalides  + Figure .2[Al2Cl7] and (CuBi8)[AlCl4]3 were accessed by reacting stoichiometric amounts of Bi, BiCl3, with CuCl in the IL [BMIm]Cl⋅4 AlCl3 at 180 °C; (CuBi8)3+ is the first intermetallic bismuth polycation with a 3d metal atom.4]− or/and the [Al2Cl7]− ion becomes part of the final product to balance the (CuBi8)3+ cluster cation. Moreover, one of the chloride ions of the [AlCl4]− group coordinates to the copper atom, thereby completing its 18‐electron count. Further investigations have shown that the (CuBi8)3+ cluster cannot be obtained either in molten AlCl3 or in ILs containing deficient/excess AlCl3, thus showing the indispensable role of the IL and a suitable Lewis acid content.In another synthesis, the two compounds 3⋅3 NH4) was produced in a ChCl/urea eutectic mixture  as the reaction media for the ionothermal synthesis of new zeolites.To date, the 1:2 mixture of choline chloride and urea  is the most widely investigated DES in the literature. Investigations have shown that heating at 125–225 °C usually leads to decomposition of the urea in ChCl/urea, thereby resulting in the reactivity of ChCl/urea at high temperatures.e Figure .[6] Th4  frameworks can also be successfully synthesized using various DESs.[Metal phosphate MPOous DESs.176 The 3CoClP4O16][C5H13NOH]2, SIZ‐13). The choline cations fill the interlayer space without significant chemical modification. However, the chloride ions from choline chloride are incorporated into the structure of SIZ‐13 through the formation of covalent Co−Cl bonds. Such metal–chlorine bonds have not been found in the hydrothermal synthesis because of their sensitivity to hydrolysis, but the water in DESs tends to be less reactive because of strong interactions with anions of the DESs.Cl2 crystals with an open structure can be obtained when the Ni2+:ChCl/urea solution is heated in a sealed vessel 6]Cl2 precursor. When the Ni2+:ChCl/urea solution is thermally treated under an open system, however, the ammonia released from the urea is removed from the reaction solution, which leads to the formation of the flower‐like α‐Ni(OH)2 when a small amount of water is added to the solution under heating .In addition to the well‐studied ChCl/urea‐based DES, other types of DESs may also be used as reactive reagents for the formation of inorganic materials. A family of binary metal sulfides, such as Bi3)3⋅9 H2O as a starting material in a ChCl/glycerol (1:2) DES  composite shows high activity for the hydrogen evolution reaction. This strategy based on phosphonium ILs provides a remarkable advantage for the efficient synthesis of metal phosphides. Ruck and co‐workers reported the synthesis of copper‐deficient Cux3−P (0.1<x<0.7) from elemental precursors in halide ILs (e.g. [P66614]Cl).− or [PF6]− anions gives a fluorine source for the synthesis of metal fluorides, thereby avoiding the use of toxic and harmful HF, NaF, or NH4F. The C2‐position of the 1,3‐dialkylimidazolium cation shows reactivity towards chalcogens  for the formation of the corresponding imidazole‐2‐chalcogenones, especially in the presence of a base. In addition, phosphonium ILs can react with chalcogens at high temperatures to generate the corresponding trialkylphosphane chalcogenides. These formed imidazole‐2‐chalcogenones or trialkylphosphane chalcogenides can be further applied as chalcogen sources for the preparation of metal chalcogenides. When some porous materials such as zeolites, MOFs, and polycationic/polyanionic compounds are synthesized by an ionothermal approach, either the cation or anion of the IL can be incorporated in the channels of the products to balance the charged frameworks and can also serve as structural templates. In the case of DESs, one or more of their components may decompose to form in situ templates for the formation of metal phosphate frameworks or act as reactive species for the synthesis of functional nanoparticles .Metal‐containing ILs represent a promising class of metal sources. The IL properties can be tailored by varying the ligand structures and the incorporated metal ions, which enables the formation of inorganic nanoparticles with diverse sizes and morphologies. Basic ILs are usually employed to replace the traditional bases, such as NaOH, KOH, or NaThe chemical reactivity of ILs and DESs in inorganic synthesis should not be underestimated. Furthermore, the reactive properties of the ILs and DESs in the reactions can be used as a synthetic tool to prepare inorganic materials that are difficult or even impossible to obtain by traditional synthetic routes. In this regard, it is important to have an in‐depth understanding of the interaction of ILs or DESs with reactants and solutes, and thus fully understand the reaction mechanism for the directed use of ILs and DESs for the preparation of inorganic materials.The authors declare no conflict of interest.Tao Zhang obtained his PhD in inorganic chemistry from the Technische Universität Dresden in 2018 under the supervision of Prof. Michael Ruck. He then joined to the Institute of Process Engineering, Chinese Academy of Sciences in 2019 as an Associate Professor. His research interests are concerned with the synthesis of functional materials in ionic liquids.Thomas Doert received his PhD from the University of Düsseldorf in 1994 with Prof. Peter Böttcher. He then moved to the Technische Universität Dresden, where he is now Adjunct Professor. He was visiting scientist at Stockholm University as well as Guest Professor at Strasbourg University and Shanghai University of Engineering Science. His research interests cover crystallographic aspects of solid‐state chemistry, solid‐state chemistry of chalcogenides, layered materials, and frustrated magnets.Hui Wang is a professor at the Institute of Process Engineering of the Chinese Academy of Sciences. She received her PhD from the University of the Chinese Academy of Sciences in 2010 with Prof. Zengxi Li. In the same year, she joined Professor Robin D. Rogers’ Group at the University of Alabama as a postdoctoral research fellow. In 2015, she moved to the Institute of Process Engineering, Beijing. Her research interests focus on the properties of ionic liquids and the applications of ionic liquids in green chemical processes.Suojiang Zhang received his PhD from Zhejiang University in 1994 with Prof. Shijun Han. He has been a professor at the Institute of Process Engineering of the Chinese Academy of Sciences since 2001, and was elected as a member of the Chinese Academy of Sciences in 2015. He is currently Director General of the Institute of Process Engineering and Fellow of the Royal Society of Chemistry. His research interests focus on the designed synthesis of ionic liquids and their applications in green chemistry and green process engineering.Michael Ruck received his PhD from the University of Stuttgart in 1991 with Prof. Arndt Simon. After his habilitation at the University of Karlsruhe in 1997, he was a Heisenberg fellow of the German Science Foundation. Since 2000 he has been Full Professor of Inorganic Chemistry at the Technische Universität Dresden, where he has served as Dean of the Faculty of Science and Vice Rector. He has repeatedly been appointed a Fellow of the Max Planck Society and awarded the Steinhofer Research Award and the Will Kleber Commemorative Coin. His research interests include solid‐state chemistry and sustainable material syntheses.