To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1‐mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers.Between May 2016 and March 2017, 8 volunteers  and 8 pigs  underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method.P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope . ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA . No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs  and by MOLLI5s(3s)3s for volunteers  but did not increase as measured by SASHA.In pigs, ECV in normal myocardium was not different between radioisotope  and SASHA (21 ± 2%; Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI‐sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence. Extracellular volume fraction (ECV) is affected by disease processes, including diffuse myocardial fibrosis, general edema from myocarditis, or myocardial storage disease, and could potentially be used to identify and grade the severity of these pathologies. Measurements of ECV have historically only been possible using experimental techniques,Cardiovascular MR (CMR) can be used to accurately measure ECV by comparing T1 recovery‐times measured before and after contrast administrationThe major advantage of measuring ECV is that it supplies an absolute, physiological value as opposed to conventional CMR methods which rely on relative differences in signal intensity within the myocardium. This means that ECV measurements could improve the ability to detect diffuse processes affecting the entire myocardium and subtle changes which may not be readily apparent by visual assessment. The usefulness of this method, specifically to differentiate disease from health in unclear cases, is therefore highly dependent upon accurate and precise measurements of normal values, whereas this is of less importance in clear cases of disease. While it is currently known that different T1‐mapping sequences produce different ECV values,99mTc), bound to an extracellular carrier molecule (DTPA). Activity measurements were normalized to the activity of plasma, serving as a 100% ECV calibration point to calculate ECV independently of CMR measurements. Clinical sequences, however, have not been verified against an independent reference standard to date.The first experimental studiesThe aim of this study was, therefore, to verify ECV measurements obtained with clinically applicable T1‐mapping techniques, including SASHA and variants of MOLLI, in a porcine model against a radioisotope‐based reference standard and to relate the results to those obtained by the same pulse sequences in healthy human volunteers.2The data in this study were collected between May 2016 and March 2017. The experimental part of the study was approved by the regional ethics committee for animal experiments (registration number M94‐14), whereas the volunteer part was approved by the regional ethics committee in Lund, Sweden, and written informed consent was acquired from all subjects (registration number 2013/891).2.1Pigs of 40‐50 kg  was administered. Animals were monitored with regards to arterial blood pressure, heart rate, electrocardiogram, pulse‐oximetry, temperature, and arterial blood gas. During the experiments a slow infusion of Ringer's Acetate  was maintained. Nondepolarizing muscle relaxant  was administered as needed to minimize respiratory artefacts during imaging.99mTc‐DTPA was administered intravenously and allowed to circulate for 15 min. The animals were then euthanized by infusion of a saturated potassium chloride (KCl) solution, after which hearts were explanted and sliced into 5‐ to 10‐mm‐thick slices. One 3‐mm‐diameter punch biopsy was taken from each of 16 sectors in 1 basal, 1 mid‐ventricular, and 1 apical slice according to the AHA 17‐segment model,After sedation and preparation, the pigs were transported to the MR department for imaging. Blood was sampled for hematocrit (Hct) at arrival, before, 30 min after, and 60 min after contrast agent‐injection to ensure Hct did not change between pre‐ and postcontrast T1‐map acquisitions.2.2Volunteers with no history of systemic or cardiac disease were included  using an 18‐channel receiver coil optimized for CMR applications (body array and spine array). Three MOLLI2.4Radioactive counts were measured from the punch biopsies taken from the explanted porcine hearts and from plasma as well as whole blood after weighing each sample separately. Visible droplets of blood were gently removed from the biopsies taking care to avoid the effect of capillary action on the myocardium. An automatic gamma counter  was used to measure radioactivity over 5 min, adjusting measures for the half‐time of 99mTc. Samples were corrected for detector dead time and rerun if dead time exceeded 10%. Weighing was performed using calibrated precision scales  with a least measurable weight of 0.097 g at an allowed error of 0.1%. The number of counts in the myocardial biopsies was normalized to their respective weight. The average value of all 16 biopsies were used for each pig. The activity of plasma was used as a reference of 100% ECV. ECV fraction was calculated by dividing the weight‐normalized activity (counts) of the myocardial biopsies with the weight‐normalized activity of plasma:The activity of whole blood was normalized to the activity of plasma to calculate Hct and was compared with directly measured Hct values as an internal quality control. For 1 pig, there was visible hemolysis in the plasma sample. For this pig, the radioactivity in whole blood was divided by 1 minus Hct as given by the laboratory to be used as the plasma reference. ECV fraction for this pig was 21%.An additional experiment was performed to determine whether the time from termination and explantation of the heart was of importance.Immediately after termination with KCl, a chunk of the left ventricular anterolateral wall was excised, from which a sample was put in a test tube and weighed. This procedure was repeated 17 times over the first 10 min and an additional 5 times over the first hour. The radioactivity of the samples was then measured as described above and later normalized to the weights of the samples.2.5CMR images were analyzed using Segment 2.0 R5453 .Late Gd enhancement and contrast‐enhanced bSSFP images were visually assessed to ensure no focal myocardial edema or fibrosis was present in the pigs.2.6P‐value < 0.05 was considered to indicate statistical significance. Results are presented as mean ± standard deviation. T1‐values are presented to the nearest 10 ms to improve readability, reflecting that there is currently no reasonable way of achieving higher precision than that.Statistical analyses were performed using SPSS Statistics Viewer . Linear regression was performed to analyze changes in ECV over time after contrast, both including and excluding data from the first 10 min after contrast injection to account for the time it takes to equilibrate Gd over different compartments.33.1Eight pigs and 8 volunteers were included; see Table 3.2P = 0.150) while MOLLI 5(3b)3, MOLLI 5(3s)3, and MOLLI 5s(3s)3s all showed significantly higher ECV than both radioisotope  and SASHA .ECV results by radioisotope and CMR are shown in Figure P = 0.022, P = 0.033) while MOLLI 5s(3s)3s showed no significant difference from SASHA . No difference in ECV by radioisotope was seen between slice positions .Similar to this, ECV in the myocardium of healthy human volunteers was 26 ± 3% by MOLLI 5(3b)3, 26 ± 3% by MOLLI 5(3s)3, 25 ± 3 by MOLLI 5s(3s)3s and 22 ± 3% for SASHA. There was a statistically significant difference of 4% between MOLLI 5(3b)3 and SASHA as well as between MOLLI 5(3s)3 and SASHA . Native T1‐times of myocardium in pigs were also significantly higher by SASHA than for the MOLLI sequences . A similar pattern was seen in volunteers where SASHA showed statistically higher T1‐times of blood compared with MOLLI sequences  as well as higher T1‐times of myocardium .Example images from the T1‐mapping sequences are shown in Figure 3.42 = 0.42; P < 0.001), MOLLI 5(3s)3 , MOLLI 5s(3s)3s , and SASHA . When excluding data from the first 10 min from the analysis, there was still an increase in ECV over time for pigs using MOLLI 5(3b)3  and MOLLI 5(3s)3 , while no increase over time was seen for MOLLI 5s(3s)3s or SASHA .The ECV plotted against time after contrast injection for pigs and volunteers is shown in Figure 2 = 0.09; P = 0.047) and MOLLI 5s(3s)3s  but not for MOLLI 5(3s)3 or SASHA . When excluding data from the first 10 min, there was still an increase in ECV over time for MOLLI 5s(3s)3s  but not for MOLLI 5(3b)3, MOLLI 5(3s)3, or SASHA . No significant change or trend toward an increase or decrease in ECV fraction by radioisotope was seen over the first hour after termination .For volunteers, there was a smaller increase over time for MOLLI 5(3b)3 , respectively, by CMR.Flett et al used histological measurements of collagen fraction to validate the use of an early version of current clinically used T1 sequences.The difference in native T1‐times seen between MOLLI and SASHA corroborates the results from several phantom‐studies showing that MOLLI underestimates T1 slightly while SASHA is more accurate.T1∗‐correction.It should be noted that SASHA is also subject to effects causing underestimation of T1, albeit to a lesser degree than MOLLI, and that the 3‐parameter fitting for SASHA is the least sensitive to magnetization transfer.myocardial postcontrast 500 ms, T1myocardial precontrast 1000 ms, T1Blood postcontrast 300 ms, one finds that the difference between using a T1Blood precontrast of 1600 ms (MOLLI) and of using T1Blood precontrast of 1820 ms (SASHA) is a change in ECV from 25.5% for MOLLI to 24.8% for SASHA.Thus, as per the section above, the higher ECV shown by MOLLI compared with SASHA is driven by lower myocardial postcontrast T1 values, which is incompletely compensated by lower precontrast myocardial T1 values. While precontrast blood T1 was lower for MOLLI compared with SASHA, it would not have a large enough role to explain any significant part of the difference as seen by the following example. Using Equation The current study has implications for development of T1‐mapping techniques for measurement of ECV as well as for interpreting the results of currently used techniques. It can be argued that accuracy is not essential for separating health from disease in individual patients, as long as there are reference values for the particular setup used. However, accurate measurements and an understanding of what affects them are prerequisites for method standardization and for enabling comparison of values between different clinical centers, users, and scanners. Specifically, there is a need to understand the overestimation of ECV seen for MOLLI but not in SASHA and whether it can be corrected for.4.199mTc is a commonly used radioisotope in clinical nuclear medicine due to a practical half‐life of around 6 h and for emitting photons at an energy level that falls within optimal range for gamma counters.4.2Using MOLLI, it is necessary to allow sufficient recovery of magnetization between acquisitions to achieve accurate T1; therefore, the length of the pause between inversions affects the measurements. Thus, heart rate affects the result of MOLLI sequences, where the pause is based on the number of beats but not as much when the number of seconds is used. It also follows that longer T1 needs longer pauses to allow magnetization recovery, which is the basis for using sequences with longer pause precontrast than postcontrast. When time passes after contrast injection, T1 will gradually be prolonged, as Gd is eliminated by the kidneys and T1‐measurements could be affected depending on the length of the pause between inversions. An indication that this could in fact be the case is the increase seen in ECV over time for MOLLI 53b)3 and MOLLI 5(3s)3 for the pigs  and myocardium (right column) before administration of contrast agent and over time after administration. Note the smaller spread in R1 after contrast in the pigs, which could be expected in the controlled experimental setting in young animals of the same weight and age. Note also that there are no obvious consistent differences in slope of the curves between volunteers and pigs. This indicates that there is no major difference in clearance rate of contrast agent between the groupsFIGURE S2 Relationship between extracellular volume fraction (ECV) and heart rate for the different T1‐mapping techniques in human volunteers using data from different time points after contrast, thus the precontrast T1 measurement remains the same. The heart rate in one of the volunteers stood out as being higher than the rest, the data from this volunteer has been marked with a red circle. Results from all volunteers can be seen in the plots. Excluding the outlier resulted in the following nonsignificant slopes MOLLI 5(3b)3: y = 0.00026x+0.26, P = 0.746; MOLLI 5s(3s)3s: y = −0.0012x+0.34, P = 0.141; MOLLI 5(3s)3: y = 0.00020x+0.26; SASHA: y = 0.00056x+0.20, P = 0.479FIGURE S3 Relationships between extracellular volume fraction (ECV) and heart rate for the different T1‐mapping techniques in pigs using data from different time points after contrast, thus the precontrast T1 measurement remains the same. There was no statistically significant correlation between ECV and heart rate for any of the T1 mapping techniquesFIGURE S4 Relationships between native T1 and heart rate for the different T1‐mapping techniques in pigsFIGURE S5 Relationships between native T1 and heart rate for the different T1‐mapping techniques in volunteersFIGURE S6 ECV as measured using postcontrast T1 from different time‐points after administration of contrast showing individual datapointsFIGURE S7 Postcontrast T1 values from porcine experiments for myocardium (2 left‐most columns) and for blood (two right‐most columns) showing data for each experiment individually. Note the consistently lower values of MOLLI sequences compared with SASHA for myocardiumFIGURE S8 Postcontrast T1 values in volunteers for myocardium (2 left‐most columns) and for blood (2 right‐most columns) showing the data for each volunteer individually. Note the similar pattern as in Figure 4 where MOLLI sequences show consistently lower values than SASHA in myocardiumClick here for additional data file.


Herein, a liquid‐phase hot deformation procedure, during which the Bi23 ingots are directly hot deformed with the extrusion of liquid eutectic phase, is performed to enhance the thermoelectric performance of n‐type Bi23 alloys. The deformation‐induced dynamic recrystallization is remarkably suppressed due to the reduction of nucleation sites and the release of deformation stress by liquid phase, contributing to a weakened carrier scattering and enhanced carrier mobility. The liquid eutectic phase also facilitates the rotation of grains and enhanced (000l) texture, further improving carrier mobility. In addition, the dense dislocations and lattice distortion introduced into the matrix reduce the lattice thermal conductivity. As a result, a high zT value of 1.1 at 400 K is obtained, about 75% increment over the normal one‐step hot deformed alloys. This work not only demonstrates a simple and efficient technique for achieving superior n‐type Bi2Te3‐based materials, but also elucidates the important role of liquid eutectic phase in hot deformation.Bismuth‐telluride‐based solid solutions are the best commercial thermoelectric materials near room temperature. For their n‐type polycrystalline compounds, the maximum figures of merit 3.Here, liquid‐phase hot deformation is introduced to n‐type polycrystalline Bi Their conversion efficiency is governed by the dimensionless figure of merit 2Te3‐based alloys exhibit zT ≈ 1 around room temperature.2Te3‐based alloys. For p‐type 2Te3 materials, a peak zT > 1.2 can be readily realized by nanostructuring. Recently, the liquid‐phase sintering (LPS) process, which involves sintering under conditions where solid grains are surrounded by the wetting liquid,2Te3‐based alloys. Nanoscale defects such as dense dislocations[qv: 4e] or Sb‐rich region[qv: 8b] could be introduced during LPS and play important roles in reducing κL. In addition, the texture could be enhanced after LPS,[qv: 8a] which is beneficial for the improvement of carrier mobility µH.As the state‐of‐the‐art TE materials, bismuth‐telluride‐based solid solutions have been the best commercial materials for solid‐state cooling near room temperature. Both p‐ and n‐type zone‐melted (ZM) Bi23 alloys, the LPS process has also been employed to reduce κL via introducing nanostructures into the matrix. Through LPS, a peak zT ≈ 0.98 at 370 K and a peak zT ≈ 0.7 at 398 K have been obtained by Zhang et al. and Ge et al., respectively. However, compared to the p‐type counterparts, zTs in n‐type polycrystalline Bi23 alloys are usually less than 1.0 due to the deteriorated texture and the deviation from the optimal carrier concentration resulting from the pulverization of ingots and donor‐like effect.0.06Bi2Te3.18 alloys via the hydrothermal method combined with SPS and a high zT > 1.1 at 323 K was achieved.2Te3−xSex nanoplates and obtained a zT of 1.23 at 480 K for the sintered sample.For n‐type BiL in n‐type Bi2Te3‐based materials. By applying a twice HD on n‐type ZM Bi2Te2.79Se0.21 ingot, Hu et al. induced multiscale microstructures into the matrix to strongly scatter phonons and obtained a peak zT ≈ 1.2 at 357 K.L from 1.2 to 0.8 W m−1 K−1 and reported on a peak zT ≈ 1.1 at 625 K in the hot deformed Bi1.85In0.15Te2Se alloys.µH by texturing in the HD process, peak zTs varying from 1.04 to 1.3 can be realized in different n‐type HD Bi2Te3‐based materials. Note that, most of them with peak zT ≥ 1.1 were obtained by multiple HD. Nevertheless, such an HD procedure is complicated, which includes ingot pulverization by BM, powder sintering by HP or SPS, and repeated hot deformation (up to three times), leads to considerable energy consumption. Meanwhile, the uncontrollable volatilization of Te or Se during multiple high‐temperature processing and the severely increased nH caused by the donor‐like effects during ingot pulverization could also result in poor repeatability in the HD Bi2Te3‐based alloys. Hence, it is necessary to develop a new technique with a simpler and milder process to prepare superior n‐type Bi23 materials.In recent years, the hot deformation (HD) process has been successfully applied to enhance texture as well as reduce κ23 alloys. The lamellate Te‐rich eutectic phase is introduced into the Bi23‐melted ingot. This ingot is then directly hot‐deformed in a larger graphite die at a temperature above the eutectic point. In this case, the Bi23 solid grains are initially surrounded by the liquid eutectic phase and then gradually deformed with the extrusion of liquid. Compared to the multiple HD procedure, the process flow in LPHD technique is much shortened. During one‐step LPHD, the deformation‐induced dynamic recrystallization is remarkably suppressed due to the reduction of nucleation sites at interfaces and the release of deformation stress in the matrix, contributing to a weakened electron scattering and hence an enhanced carrier mobility µH. In addition, the µH is further improved by texturing during LPHD. Meanwhile, a significant reduction of the lattice thermal conductivity is also realized in the LPHD sample as a result of the enhanced phonon scattering by dense dislocations as well as lattice distortion. Finally, a high zT value of 1.1 at 400 K is obtained in the n‐type LPHD Bi23 alloys. These results not only demonstrate a simple and energy‐saving technique for synthesizing high‐performance n‐type Bi2Te3‐based materials, but also emphasize the significance of liquid eutectic phase in tuning materials' microstructures.Herein, we report a novel liquid‐phase hot deformation (LPHD) technique to enhance the TE properties of n‐type Bi2Figure2Te2.7Se0.3 melted ingot (named as M‐0Te) has a pure rhombohedral R3m phase, while the Bi2Te2.7Se0.3 + 16 wt% Te‐melted ingot (named as M‐16Te) has a little Te second phase remaining in the Bi2Te3 matrix. The Te peaks (indicated by the red arrows) are hard to be recognized from the normal XRD patterns but can be clearly identified in the logarithmic XRD intensity versus 2θ patterns.The X‐ray diffraction (XRD) patterns in Figure2Te2.55Se0.33 by energy‐dispersive spectrometer  and then corrected to be Bi2Te2.66Se0.26 by electron probe microanalysis , while the darker phase (with more Te) in Figure 2Te3–Te phase diagram in Figure 2Te3–Te. To verify it, a differential scanning calorimetry (DSC)– thermogravimetric analysis (TGA) test is performed on the M‐16Te, and a distinct endothermic peak at 692.3 K is detected , very close to the eutectic temperature (686 K) in Figure 2Te2.66Se0.26 alloys and eutectic phase of Bi23–Te. Undoubtedly, the Bi23–Te eutectic phase would also exist in our other Bi2Te2.7Se0.3 + x wt% Te‐melted ingots (x from 1 to 32) according to Figure The scanning electron microscopy (SEM) backscattered electron (BSE) image Figure2a and 23 bulk is accompanied by the extrusion of liquid eutectic phase. Hence, this procedure is named as liquid‐phase hot deformation and the picture of extruded eutectic phase is shown in Figure S3 (Supporting Information). For simplicity, the HD Bi2Te2.7Se0.3 sample is named as HD‐0Te and other HD Bi2Te2.7Se0.3 + x wt% Te (x ≥ 1) samples are named as LPHD‐xTe, respectively. The XRD patterns in FigurexTe samples are pure Bi2Te3 phase without any detectable Te second phase remaining. The compositional homogeneity in all samples is confirmed by EDS mapping and a typical result of LPHD‐16Te is shown in Figure S4 (Supporting Information). The real composition of LPHD‐16Te is identified as Bi2Te2.70Se0.27 by EPMA, which has a slightly higher Te and Se contents compared to the Bi2Te2.66Se0.26 melted precursor ingot.Since the HD temperature is above the eutectic point, the deformation of BiF of (000l) plane was calculated using the Lotgering method,Tablex in LPHD‐xTe, F first increases from 0.09 to 0.20 and then slightly decreases to 0.17, indicating an initially enhanced and then weakened texture in the LPHD samples (the nonmonotonic variation of F will be discussed later). A comparison of SEM microstructure between HD‐0Te and LPHD‐16Te is also presented in FigureF results.To evaluate the texture degree, orientation factor nH from 4.1 × 1019 to 5.0–6.4 × 1019 cm−3 after LPHD is shown in Figure2Te2.4Se0.6 alloys.2Te2.66Se0.26 to Bi2Te2.70Se0.27) indicates that a small number of Te and Se atoms in the liquid eutectic phase may diffuse into the Bi23 grains during LPHD and provide electrons (in the formation of TeBi• antisite defects). Nevertheless, when increasing x from 1 to 32, nH has little change, which may be caused by the relatively small equilibrium concentration of TeBi• in n‐type Bi23 alloys. The variation of room temperature carrier mobility µH with x is also presented in Figure µH first increases and then decreases with x, reaching µH ≈ 196 cm−2 V−1 s−1 for the LPHD‐16Te sample (the nonmonotonic variation of µH will be discussed later). Low‐temperature Hall measurement  shows that the intrinsic conduction near room temperature is obvious in the HD‐0Te sample, which will result in an incorrectly calculated µH. Even so, the enhanced µH by LPHD could be verified from the µH data in the extrinsic region (T < 150 K), consistent with the F results in Table 3‐doped Bi2Te2.7Se0.3 HD sample was also prepared, and its carrier transport properties are labeled in Figure µH of LPHD samples is still higher than the HD sample, demonstrating the importance of liquid eutectic phase for enhancing µH during the LPHD process.An increase of µH and orientation factor F between LPHD Bi2Te2.7Se0.3 samples and other reported HD Bi2Te2.7Se0.3 or Bi2Te2.79Se0.21 samples are summarized in Figure S5b (Supporting Information). In the single parabolic band (SPB) model, µH is readily influenced by the reduced Fermi energy η according to the following equationjF(η) is the Fermi integral of order j, µ0 is the nondegenerate mobility and related to the carrier relation time τ0 (affected by the carrier scattering), transport effective mass mI∗, and electron charge e as followingA comparison of Hall mobility In the SPB model, η could be calculated by α according to the following equationµ0 of all samples in Figure S5b (Supporting Information) was calculated according to Equations µ0 at a fixed F. Particularly, although the HD Bi2Te2.79Se0.21 samplesF values, their µ0 is still less than that of the LPHD Bi2Te2.7Se0.3 alloys. It should be noted that at a constant F value, µ0 is only related to τ0 and mI∗, which is described in Equation mI∗ among these samples could be ignored. Therefore, the remarkably enhanced µ0 by LPHD should arise from the increased carrier relation time τ0, which indicates a reduced carrier scattering in the LPHD samples.In order to exclude the effect of η on carrier mobility, the nondegenerate mobility FigureTo verify this conjecture, further microstructural investigations on our HD‐0Te and LPHD‐16Te samples was carried out by electron backscattered diffraction (EBSD). The results are shown in µH. The improved µH also results from strongly texturing during LPHD. In Figure l) preferred orientation, and it is easy to find that the LPHD sample has more enhanced (000l) texture. This is further demonstrated by the pole figure (POF) and inverse pole figure (IPF) results in Figurel) texture.Figure2Te3 alloys, more highlighted regions located at the top of ODF sections (Φ = 0) indicate stronger texture along the (000l) direction. More detailed ODF analysis can be found in Figure S7 (Supporting Information).In contrast, the LPHD‐16Te sample has more bar‐shaped grains with a relatively homogeneous distribution of grain size, as shown in Figure µH. The former could be well illustrated based on the dynamic recrystallization theory. In a normal hot deformation process, dynamic recrystallization takes place during straining as long as the temperature is heated above half of the melting point of samples. The recrystallized grains are produced by nucleation and growth of crystallites in the vicinity of grain boundaries and the driving force is the stored energy induced by the plastic deformation. Hence, HD‐induced recrystallized grains could be readily found in the HD‐0Te sample . Due to the enhanced σ, κe roughly increases with x in the LPHD‐xTe samples. Figure L calculated by κ – κe. An obvious decrease of room temperature κL is observed in the LPHD samples. In particular, the minimal room temperature κL ≈ 0.43 W m−1 K−1 is achieved at x = 24, almost 50% reduction than that of HD SbI3‐doped sample. As mentioned above, compared to the HD‐0Te sample, although coarse grains are refined in the LPHD‐16Te sample, the number of fine recrystallized grains is also remarkably decreased, contributing to a reduced total grain boundary length in the LPHD‐16Te sample. In this case, low‐frequency phonon scattering by grain boundary should be weakened in the LPHD sample. Therefore, the reduction of κL by LPHD must come from other reasons.The total thermal conductivity κ of HD‐0Te and LPHD‐L in Bi2Te2.7Se0.3 alloys, further microstructure observation is conducted by a transmission electron microscope (TEM), and the results are shown in FigureL. In contrast, for LPHD sample, although the deformation‐induced dislocations and lattice distortion are considerably decreased by the extrusion of liquid eutectic phase, these defects can always remain in the matrix due to the remarkable suppression of recrystallization. As a result, strong scattering of phonons is realized in the LPHD samples, contributing to a remarkable reduction of κL.In order to clearly illustrate the influence of LPHD on the κzTs, for all HD and LPHD Bi2Te2.7Se0.3 samples are presented in Figurex from 0 to 32, the maximum zT first increases and then decreases. The highest zT value around 1.1 at 400 K is obtained for the LPHD‐16Te sample, about 75% increment over the HD SbI3‐doped one, even though both of them have the same nH ≈ 5.0 × 1019 cm−3. As aforementioned, liquid‐phase hot deformation could effectively suppress the dynamic recrystallization and enhance the texture, both resulting in a remarkable enhancement of carrier mobility. Meanwhile, dense dislocations and lattice distortion are also introduced into the LPHD samples, contributing to an obvious reduction of κL and further enhancement of zT. A comparison of maximum zT values among LPHD‐16Te sample and other reported Bi2Te3−xSex alloys is presented in Figure zT could be obtained by LPHD technique. Although zTs in some multiple HD alloys are slightly higher than zT in the LPHD sample, the process flow of one‐step LPHD technique is much shorter, which makes it a more efficient and energy‐saving route for large‐scale production of superior n‐type Bi23 materials.The dimensionless figures of merit, 323 alloys. The Te‐rich eutectic phase is introduced into the Bi23 ingot at the melting stage and plays important roles in subsequent hot deformation stage. First, the nucleation sites and stored energy for dynamic recrystallization are both reduced due to the wetting and extrusion of liquid eutectic phase, leading to a decrease of recrystallized grains and hence weakened carrier scattering, which is beneficial for an enhanced carrier mobility. Second, grain rotation along the (000l) plane becomes easier with the help of liquid phase, contributing to a stronger texture and further boosted µH. Third, lattice thermal conductivity is also simultaneously decreased by the dense dislocations and lattice distortion introduced during LPHD. All these effects contribute to a high zT ≈ 1.1 at 400 K in the n‐type LPHD Bi23 alloys. This work demonstrates a simple technique for achieving superior n‐type Bi2Te3‐based materials, which is much more efficient and energy saving compared to the multiple HD process.Here, a liquid‐phase hot deformation procedure is successfully performed to enhance the thermoelectric performance of n‐type Bi42Te2.7Se0.3 + x wt% Te  and sealed into φ 12.7 mm quartz tubes evacuated to 10−3 Pa. The mixtures were subsequently melted at 1173 K for 10 h in a furnace and rocked every 2 h to ensure the composition homogeneity. The quartz tubes were sufficiently rocked before taken out from the furnace and then cooled in the air. The conical bottom part of the obtained ingot was cut off and the remained φ 12.7 mm cylindrical ingot was directly hot‐deformed in a larger φ 20 mm graphite die at 773 K for 30 min with 80 MPa uniaxial pressure. The HD direction was parallel to the axial direction of the cylinder. Finally, disk‐shaped HD samples with high densities  were required.Bi (5 N), Te (5 N), Se (5 N) element chunks were weighted according to the stoichiometric Bi−1 under Ar atmosphere.The phase structures of all samples were evaluated by the XRD on a Rigaku D/MAX‐2550P diffractometer. The freshly fractured surfaces of bulk samples and the microstructure of melted ingots were observed by SEM (Hitachi S‐3700N) equipped with an EDS. The chemical compositions were investigated by EDS and checked by EPMA  using a wavelength dispersive spectroscope (WDS). The TEM observation was performed on FEI TF20 microscopes, and the TEM samples were prepared by the dual‐beam FIB equipment . The samples for EBSD measurement were first grinded and then mechanically polished by diamond paste (3 in roughness) for about 15 min and finally fine polished by oxide polishing suspension solution for 30 min with an applied load of 60 N. The EBSD analysis was performed on a dual‐beam focused ion beam  using a Hikari S/N 1040 camera (TSL/EDAX). EBSD data acquisition and analysis were performed by the OIM Data Collection software and OIM Analysis 7 software, respectively. The DSC and TGA analyses were simultaneously carried out on a TA Instrument SDT Q600 thermal analyzer with a heating rate of 10 K minDρCP, where ρ is the density estimated by an ordinary dimension‐and‐weight method, CP is the specific heat calculated by the Dulong–Petit law, and D is the thermal diffusivity measured by a laser flash method on a Netzsch LFA 467 instrument with a Pyroceram standard. The samples for D measurement were prepared using the same method with Xie et al.RH from 10 to 300 K were measured on a Mini Cryogen Free Measurement System . Then the Hall carrier concentration nH and Hall mobility µH were calculated via nH = 1/eRH and µH = σRH, respectively. In particular, all thermoelectric properties were measured along the in‐plane direction of samples.The electrical conductivity σ and Seebeck coefficient α were measured on a commercial Linseis LSR‐3 system using a differential voltage/temperature technique and a DC four‐probe method. The thermal conductivity κ was calculated by using κ = The authors declare no conflict of interest.SupplementaryClick here for additional data file.


Besides exploring reactivity trends and comparing them to aliphatic C–X activation, we aim at uncovering the physical factors behind the activity and selectivity. Our results show that barriers for arylic C–X activation are lower than those for the corresponding aliphatic C–X bonds. However, trends along bonds or upon variation of ligands are similar. Thus, bond activation barriers increase along C–Cl < C–H < C–C and along Pd < Pd(PH3) or Pd(PH2C2H4PH2) < Pd(PH3)2. Activation strain analyses in conjunction with quantitative molecular orbital theory trace these trends to the rigidity and bonding capability of the various C–X bonds, model catalysts, and ligands.We have quantum chemically explored arylic carbon–substituent bond activation via oxidative insertion of a palladium catalyst in C An important class of catalytic processes is constituted by transition-metal-catalyzed cross-coupling reactions which furnish new carbon–carbon bonds  by oxidative addition to a transition metal complex. This reaction step plays an essential role in the selectivity and efficiency of the overall catalytic cycle. The oxidative addition can in principle proceed via various reaction mechanisms, for instance, the concerted pathway. This pathway is an associative substitution reaction in which R–X binds first as a σ complex and then undergoes R–X bond breaking as a result of strong back donation from the metal d orbitals into the σ*R–X orbital. Another possible pathway proceeds analogously to the well-known bimolecular nucleophilic substitution. A direct nucleophilic attack of the metal center at the more electropositive atom of the R–X bond by donating the catalyst’s d electrons into the substrate’s σ* orbital, forming an [M–R]+ species and an X− leaving group.Catalysis plays a key role in many industrial processes, as well as in the synthesis of various biologically active compoundsnds Fig. 4,5. The 19. Earlier theoretical studies have investigated the oxidative insertion of numerous d10 transition-metal catalysts into various aliphatic C–X bonds17. Additionally, several concepts were introduced on how bond-activation barriers of d10-metal complexes depend on and can be tweaked through, the electronic and steric properties of the metal center and the ligands of the catalyst complex17. Furthermore, previous studies have shown that solvation does not alter the trends in oxidative-insertion reactivity and selectivity along various aliphatic bonds and model catalysts compared to the gas phase19.Due to the importance of the oxidative addition, extensive experimental and theoretical research has been committed to this reaction step3), Pd(PH3)2, and Pd(PH2C2H4PH2)  program. Reactivity trends have been analyzed using the activation strain model (ASM) in conjunction with quantitative canonical (Kohn-Sham) molecular orbital theory and a matching canonical energy decomposition analysis (EDA) that quantifies the various features in the bonding mechanism. First, we compare the behavior and trends found for the arylic C–X activation with the previously studied aliphatic C–X bonds17. In the second part, we examine the activation of the C–H bond of benzene, the C–Cl bond of chlorobenzene, and the exocyclic C–C bond of toluene by a bare palladium atom. At last, we investigate the effect of introducing various phosphine ligands on the different reaction pathways.Herein, we quantum chemically explore and analyze reactivity and selectivity trends in arylic carbon–substituent bond activation of C–H, C–Cl, and C–C bonds in benzene, chlorobenzene, and toluene to palladium catalysts Pd, Pd-induced C–H bond activation. In that case, arylic C–H activation proceeds via a slightly higher barrier than aliphatic (methane) C–H activation, 17.1 and 15.7 kcal mol−1, respectively. Secondly, the trends in reaction barrier, for a given palladium catalyst, along the three C–X bonds is similar for the arylic and aliphatic C–X bonds and decreases in the order C–C > C–H > C–Cl17. Thus, the activation of the ethane and toluene C–C bonds by a palladium catalyst occur with the highest barriers, contrarily, the activation of the chloromethane and chlorobenzene C–Cl bonds have the lowest barriers.Our ZORA-BLYP/TZ2P results are collected in Table 3), to two phosphines ((PH3)2), to the chelating 1,2-ethanediyldiphosphine (PH2C2H4PH2). These phosphine ligands have both σ-donor and π-acceptor properties. Coordinating these ligands to the catalyst increases the reaction barriers of all arylic C–X bond activations , and Pd(PH3)2. However, when we coordinate a chelating ligand to the catalyst, i.e., Pd(PH2C2H4PH2), the reaction barrier drops to 13.6 kcal mol−1, that is, below the barriers for Pd(PH3) and Pd(PH3)2. In the case of C–Cl and C–C bond activation, the barriers for the chelate complex Pd(PH2C2H4PH2) also drop below the one of Pd(PH3)2 but not below that for Pd(PH3). Thus, the trend in barriers is: Pd < Pd(PH3) or Pd(PH2C2H4PH2) < Pd(PH3)2.Furthermore, we have examined the effect of various phosphine ligands on the reactivity of the catalyst, by changing the catalyst from bare palladium to a palladium metal center with ligands varying from one phosphine  for arylic C–H, C–Cl, and C–C activation by a bare Pd atom are all more stable than their aliphatic counterparts Table . The hig3 ligand to Pd destabilizes the RC by 5 kcal mol−1, whereas, adding a second phosphine ligand reduces this RC’s stability with another 14 kcal mol−1. The substantial reduction of RC stability, when going from a monoligated to a bisligated palladium-phosphine catalyst, is due to the loss of the energetically favorable η2 interaction between the catalyst and the phenyl ring of the substrate as the steric crowding around the metal center increases. Going from Pd(PH3)2 to Pd(PH2C2H4PH2), the RC becomes more stable as there is again sufficient room for entering into a favorable η2 interaction between palladium and the substrate’s π system at C1 and C2. A similar trend in reactant complex stability is found for the activation of the arylic C–H and C–C bonds.The introduction of ligands coordinated to the palladium catalyst has the effect of weakening reactant complexes and pushing up reaction barriers Table . In the 40. This model is based on the idea that the energy of a reacting system, that is, the reaction potential energy surface, is described with respect to, and understood in terms of the properties of, the original reactants. It considers their rigidity and the extent to which the reactants must deform during the reaction plus their capability to interact as the reaction proceeds. Thus, we decompose the total energy, ΔE(ζ), into the strain and interaction energy, i.e., ΔEstrain(ζ) and ΔEint(ζ), and projected these values onto the bond stretch of the activated C–X bond  is the energy that is necessary to deform the reactants from their equilibrium structure to the geometry they adopt in the reaction system at point ζ of the reaction coordinate. On the other hand, the interaction energy ΔEint(ζ) accounts for all the chemical interactions that occur between the deformed fragments during the reaction.In this equation, the strain energy ΔOur activation strain analyses reveal that the higher reaction barrier of the activation of the aliphatic C–X bond  scheme44:To clarify the difference in interaction energy, we have further decomposed ΔVelstat is the classical electrostatic interaction between the unperturbed charge distributions of the (deformed) reactants which is usually attractive. The Pauli repulsion ΔEPauli comprises the destabilizing interaction between occupied orbitals  due to the Pauli principle and is responsible for any steric repulsion. The orbital interaction energy ΔEoi accounts for polarization and charge transfer, amongst others, HOMO–LUMO interactions.Herein, ΔEoi and the electrostatic attraction ∆Velstat are more stabilizing for the arylic C–X activation processes  in early stages of C–X activation and the empty 5 s orbital of the palladium catalyst, associated with HOMO–LUMO energy gaps between 5.5 and 3.5 eV. When the reaction proceeds further towards the transition state, the backbonding interaction between the catalyst 4d and substrate σ*C–X orbital becomes the most important mechanism.The characteristic difference in orbital interactions at the beginning of the oxidative addition reactions  can be ascribed to differences in the bonding mechanisms between the catalyst and substrate along the reaction coordinate. The catalyst–substrate interaction for all three aliphatic reactant complexes are dominated by the donor–acceptor interaction between the filled σAt variance, for the arylic reactant complexes, the foremost donor–acceptor interaction in the reactant complex is between the filled palladium 4d orbitals and the low lying empty π* orbital of the phenyl ring, which goes with a smaller HOMO–LUMO gap of 2.7–3.3 eV and thus a more stabilizing orbital interaction. Proceeding further along the reaction coordinate, the bonding mechanism changes, from solely metal–substrate 4d → π* “backbonding” to a “forward” donation from the occupied aromatic π orbitals into the empty metal 5s.C–X orbital, just as in the case of the aliphatic C–X activation. Importantly, the σ*C–X acceptor orbital of the aliphatic C–X bond is at higher energy than that of the arylic C–X bond. Consequently, the HOMO–LUMO gap associated with the metal 4d to substrate σ*C–X interaction is larger in the case of the aliphatic C–X bond which therefore experiences a less stabilizing catalyst–substrate interaction and thus arrives at a higher barrier in the bond activation reaction.As soon as the reaction approaches the transition state, the orbital-interaction mechanism becomes, in all cases, predominantly backbonding from catalyst 4d to substrate σ*17. The low barrier for C–Cl activation is simply the result of the relative weakness of this bond. We compute homolytic bond dissociation energies for our arylic C–C and C–H bonds  that are significantly higher than that for the arylic C–Cl bond . This results in a significantly lower strain curve and thus a lower barrier for the activation of the arylic C–Cl bond.Our activation strain analyses clearly reveal the physical factors that determine the trend of a decreasing barrier along the activation of arylic C–C, C–H, and C–Cl see Fig. . These tEint. The physical origin consists of the same two factors as those found for the corresponding aliphatic C–H and C–C bonds17: (i) the methyl C–H bonds shield the C–C bond which first has to stretch before the metal can approach sufficiently closely for its dπ orbital to overlap with the σ*C–C; and (ii) the C–C bond also has to stretch in order to move the two nodal surfaces that the σ*C–C orbital has on the carbon nuclei, out of the way of the metal dπ lobes before a favorable 〈dπ|σ*C–C〉 overlap can occur. This is schematically illustrated in Fig. π|σ*C–X〉 overlaps is shown in Fig. π|σ*C–H〉 overlap as opposed to the more abrupt rise of 〈dπ|σ*C–C> after a stretch of approximately 0.3 Å.The fact that arylic C–C activation goes with a higher barrier than arylic C–H activation can be traced to a delay, along the reaction coordinate, in building up stabilizing interaction ∆3), Pd(PH3)2, and Pd(PH2C2H4PH2) , and Pd(PH3)2, and then decrease again from Pd(PH3)2 to Pd(PH2C2H4PH2) 2 complex, the palladium center has become sterically more congested. Now, it has to bend its two ligands away by up to approximately 100° to avoid steric (Pauli) repulsion with, in order to make room for, the incoming substrate. This bending goes with a substantial enhancement of the unfavorable strain curve ∆Estrain which further raises the reaction barrier provided by the total energy profile ∆E .That changes as soon as the second phosphine ligand is introduced: In the linear dsee Fig.  Note tha2C2H4PH2), the coordinating sites are pulled towards each other by the short dimethylene bridge which causes the catalyst complex to be pre-distorted. Consequently, substantially less additional bending is required for coordinating the substrate. This has a major effect on the strain curve ∆Estrain which drops markedly  proceeds with a lower activation barrier than Pd(PH3)2. Yet, the TS of the former more exothermic reaction is located a later, more product-like point along the reaction coordinate, instead of at an earlier, more reactant-like point. The reason is that the electron-donating capability of the bisligated catalyst suddenly improves, relative to that of Pd(PH3), only after the P–Pd–P angle starts bending. The effect of this phenomenon is that the resulting hybrid d orbitals are pushed up in energy and oriented more towards the substrate σ*C–X orbital, resulting in a better overlap. Thus, as we proceed along the reaction coordinate for oxidative addition to the bisligated metal complex, the interaction curve becomes steeper. This enhanced steepness pulls the TS ‘to the left’, that is, to an earlier reactant-like geometry.Finally, we wish to point out an interesting detail. Going from the monoligated to the bisligated catalyst, one can observe anti-Hammond behavior see Fig. 16. Thus,3) or Pd(PH2C2H4PH2) < Pd(PH3)2. This follows from our quantum chemical exploration of arylic carbon–substituent bond activation via oxidative insertion of a palladium catalyst in C6H5X + PdLn model systems 2, PH2C2H4PH2) using relativistic density functional theory.We find that arylic C–X bond activation proceeds consistently via lower reaction barriers than the corresponding processes for aliphatic C–X bonds. However, trends along bonds or upon variation of ligands are similar. Thus, bond activation barriers increase along C–Cl < C–H < C–C and also along Pd < Pd software24. The numerical integration is executed with Becke’s fuzzy cell integration scheme25. The molecular orbitals (MO) are expanded in a large uncontracted set of Slater-type orbitals (STOs). The used basis set, denoted TZ2P, is of triple-ζ quality for all atoms and has been improved by two sets of polarization functions26. The polarization functions are 2p and 3d on H, 3d and 4 f on C, P, Cl, and 5 p and 4 f on Pd. The molecular density was fitted by the Zlm fitting scheme27. The frozen core approximation has been employed using the following frozen shells: 1 s for C, [He]2p for Cl, and [Ar]3d for Pd.All calculations are based on Density Functional Theory (DFT)28. In the latter, the exchange is described by Slater’s Xα potential with nonlocal corrections due to Becke added self-consistently31, whereas correlation is treated using the gradient-corrected functional of Lee, Yang, and Parr32, added again in a self-consistent fashion. Scalar relativistic effects are accounted for using the zeroth-order regular approximation (ZORA)34. This approach was extensively tested against ab initio reference benchmarks from hierarchical series up till CCSD(T)37.Equilibrium structures and transition state geometries have been computed using analytical gradient techniques and the BLYP functional47, to be  minima (zero imaginary frequencies) or transition states (one imaginary frequency). The character of the normal mode associated with the imaginary frequency has been analyzed to ensure it resembles the reaction under consideration. To obtain the potential energy surface (PES) of the chemical process, intrinsic reaction coordinate (IRC) calculations have been performed49. The potential energy surfaces are analyzed using the PyFrag program50. Optimized structures were illustrated using CYLview51.All stationary points have been verified, through vibrational analysisSupplementary Information


Burkholderia species such as B. mallei and B. pseudomallei are bacterial pathogens causing fatal infections in humans and animals (glanders and melioidosis), yet knowledge on their virulence factors is limited. While pathogenic effects have been linked to a highly conserved gene locus  in the B. mallei group, the metabolite associated to the encoded polyketide synthase, burkholderic acid , could not explain the observed phenotypes. By metabolic profiling and molecular network analyses of the model organism B. thailandensis, the primary products of the cryptic pathway were identified as unusual cyclopropanol‐substituted polyketides. First, sulfomalleicyprols were identified as inactive precursors of burkholderic acid. Furthermore, a highly reactive upstream metabolite, malleicyprol, was discovered and obtained in two stabilized forms. Cell‐based assays and a nematode infection model showed that the rare natural product confers cytotoxicity and virulence. Virulence factor: The true effector molecules of a disease‐determining biosynthetic gene cluster from diverse pathogenic bacteria were discovered. Polyketides equipped with a cyclopropanol warhead show high chemical reactivity and strong potency in a eukaryotic infection model Caenorhabditis elegans. The chemical relationships between all the complex polyketides were decrypted. Infections with B. mallei, transmitted from horses, lead to glanders, a highly contagious zoonotic disease which shows up to 95 % mortality when untreated, and even 50 % when treated with antibiotics.B. pseudomallei may infect various cell types and evade the immune system, causing melioidosis.B. pseudomallei typically last longer than five months.B. mallei and B. pseudomallei have been classified as potential biological warfare agents.Burkholderia lethal factor 1 (BLF1),bur/mal gene locus m/z value of 1  for the loss of the respective m/z values compared to the overexpression strain. Through this approach we found two chromatographic peaks that correspond to an m/z of 387 in the negative ion mode in culture extracts from the overexpression strain, while the production of the same metabolites (2 and 3) was abolished in our inactivation mutant. Thus, we concluded that 2 and 3 were congeners of 1. Notably, the production of the more nonpolar congener (3) was suppressed when B. thailandensis E264 Pbur was grown at a constant pH of 6.5 in a bioreactor. By optimization of purification protocols, we succeeded in obtaining both compounds in pure form .To identify congeners of 18H28O7S for both compounds. Compared to 1 (C18H26O4), 2 and 3 lack one double‐bond equivalent, but are equipped with an additional sulfur atom and three additional oxygen atoms. The predicted sum formula was in full agreement with 1H and 13C NMR data for both compounds. Through a comparison of the chemical shifts, and COSY and HMBC correlations of 2 with the data for 1,2 showed the same acyl side chain as 1, consisting of an α,β‐unsaturated Michael acceptor system. HMBC correlations of an ester carbon center, resonating at δ=177.8 ppm, to three COSY‐correlated methine protons indicated a γ‐lactone substructure that accounts for one of the two remaining double‐bond equivalents. While 1 has a propionyl side chain, the corresponding spin system was absent in 2. Furthermore, the 13C spectrum of 2 showed two CH2 groups shifted to an unusual high field at δ=10.5 and 12.1 ppm, typical for cyclopropyl moieties.δ=54.0 ppm) completed the cyclopropanol substructure, which was linked to the γ‐lactone, according to HMBC correlations.HRMS data indicated a molecular formula of C3 group, which could either be a sulfite or a sulfonic acid. Owing to the instability of sulfite monoesters, a sulfonic acid would be the more likely candidate. We validated this structure proposal by comparison of the chemical shifts of the respective sulfonate‐substituted carbon atom in 2 and its attached proton with the chemical shifts of model compounds  all showing highly similar shifts at the respective atoms. Taken together, 2 represents an unprecedented cyclopropanol‐containing sulfonic acid that was named sulfomalleicyprol  we noticed a shift of the keto moiety resonating at δ=196.0 ppm in 2 to a value of δ=168.8 in 3, indicative of an ester moiety. Additionally, we detected a second proton in the α‐position to the lactone carbonyl group, whereas the other parts of 3 showed largely similar shifts compared to the NMR data of 2. Based on these data, we concluded that the acyl chain was not connected to the lactone ring (as in 2 and 1), but linked to the cyclopropyl moiety by an ester bond. COSY and HMBC data fully supported the proposed structure of 3, which was named iso‐sulfomalleicyprol  we tested whether 3 could be formed from 2 in vitro under basic conditions, as in cultures growing in shaking flasks (pH 8.2 after 48 h growth in LB medium). By LC‐HRMS monitoring we found that 3 originates from 2 when treated with phosphate buffer (pH 8.1) or K2CO3 solution .The structures of fer pH 8. or K2CO3fer pH 8. or K2CO3fer pH 8. or K2CO32 and 1 it appeared plausible that yet another, cryptic precursor could represent the true virulence factor. Therefore, we revisited the extracts of the bur overexpression mutant. To exclude the possibility that potential congeners of 1 were overlooked in our molecular network we performed a complementary approach using an all‐ion fragmentation (AIF) experiment in LC‐HRMS with Pbur extracts. The AIF data were screened employing the extracted ion chromatogram (EIC) for high‐resolution m/z values of previously identified MS fragments from 1, 2, and 3. By this approach we identified a parent mass of m/z 611.3589 (negative ion mode) through its sole dominating fragment ion with m/z 305.1758 . Subsequently, we isolated the corresponding compounds as two diastereomers by an optimized purification protocol . The deduced molecular formula of C36H52O8 from 13C and HRMS data for 4 hinted towards a dimeric structure comprising two burkholderic acid‐like subunits (C18H26O4). HMBC and COSY correlations confirmed 4 to be an adduct consisting of two connected γ‐lactones, each linked to an acyl chain. Two additional olefinic carbon atoms resonating at δ=157.5 and 132.0 ppm indicated a third α,β‐unsaturated double bond. HMBC correlations to a quaternary carbon center at δ=167.9 ppm located this double bond within one of the γ‐lactones, whereas the second γ‐lactone was saturated. The remaining four methylene carbon atoms shifted to high field  and two quaternary carbon atoms (δ=56.8 and 56.5 ppm) made up two cyclopropanol rings, each connected to one of the γ‐lactones. Thus, we elucidated structure 4 as a dimeric, cyclopropanol‐substituted congener of 1 named bis‐malleicyprol .In light of the similarly low bioactivities of 4 to various reaction conditions and monitored product formation by LC‐HRMS. Incubation of 4 with Na2SO3 yielded the previously isolated sulfonic acid 2  and iso‐malleicyprol (6).To establish a chemical correlation between the thus far isolated congeners we subjected 5/6 and 4 allowed us to study the cumulated biological activity of all three species. Cytotoxic and antiproliferative assays with purified 4 a on various cell lines showed a dramatically increased molar activity, over two orders of magnitude (110‐fold) higher than 1, originally assigned to the bur/mal assembly line  when added to the growth medium (as high as 100 μg mL−1). In stark contrast, when treated with 4 a (50 μg mL−1), no viable nematodes were observed in the corresponding survival assays  residues  should be addressed to the authors.SupplementaryClick here for additional data file.SupplementaryClick here for additional data file.SupplementaryClick here for additional data file.


Samples were characterized using SEM and EDS and the average atomic number ratios of Ca/Fe were calculated. Inhibition effects followed the trend: PESA > PAA > PASP > HPMA and PESA > PASP > HPMA > PAA for Fe3O4 and Fe2O3, respectively. Molecular dynamics simulations based on the adsorption model of the scale inhibitor on the surface and calculations of the adsorption energy between the scale inhibitor molecule and the surface revealed that the relatively high scale inhibitory effect is due to low adsorption energy between the inhibitor molecule and the surface. Density Functional Theory (DFT) calculations of the model after adsorption revealed that the relatively low adsorption energy depends on the number of H-O bonds formed as well as those with higher Mulliken population values between the scale inhibitor and the surface.This study presents the inhibitory effects of four scale inhibitors, including polyacrylic acid (PAA), hydrolyzed polymaleic anhydride (HPMA), polyepoxysuccinic acid (PESA) and polyaspartic acid (PASP), on the adsorption of CaCO As gas field sewage pipes are usually made of carbon steel, its surface readily oxidizes to Fe3O4 and Fe2O3 upon contact with sewage; Fe3O4 and Fe2O3 are the key oxidation products where scaling takes place.Water produced from gas fields is a common byproduct in natural gas production. Typically, it is discharged into a post-treatment facility via sewage pipe after being separated from natural gas. Since the water produced contains a variety of ions, insoluble solid particles readily form via chemical reactions and adhere to the inner walls of the sewage pipe with CaCO3 scale in gas fields is to add a chemical scale inhibitor . Therefore, phosphorus-free scale inhibitors such as polyacrylic acid (PAA), hydrolyzed polymaleic anhydride (HPMA), polyepoxysuccinic acid (PESA) and polyaspartic acid (PASP) have been widely used. PAA can make the shape of CaCO3 in solution irregular4 and inhibits the preferential growth surface of CaCO3 crystals4. The effectiveness of CaCO3 inhibition is proportional to the concentration of PAA4. Meanwhile, the presence of PAA reduces the amount of CaCO3 precipitation on the rotating disk electrode by 70%5. HPMA inhibits the production of CaCO3 in solution, damages the regular shape of CaCO36 and inhibits the preferential growth surface of CaCO3 crystals. Indeed, inhibition by HPMA is more effective than PAA4. PESA can also inhibit the formation of CaCO3 and damage the shape of CaCO3 in solution7. Molecular dynamics simulations suggest that PESA can adsorb on the preferential growth surface of CaCO3 crystals to inhibit their growth8. By comparing the scale inhibition efficiency, it was determined the inhibition efficiency of PESA on CaCO3 in solution was higher than that of HPMA and PAA9. PASP can also inhibit the formation of CaCO3 in solution and damage the shape of CaCO311. However, the inhibition effect of PASP in solution is inferior to that of PESA12.The main treatment method for CaCO3 in solution, while the effects of surface inhibition of CaCO3, especially on surfaces of Fe3O4 and Fe2O3, are not fully understood. In this study, we present an experimental simulation of surface CaCO3 scaling on Fe3O4 and Fe2O3 surfaces. The Ca/Fe ratios in different cases were obtained and compared with each other to evaluate the inhibition effects of the four inhibitors. We then established models of the scale inhibitor molecules with both the Fe3O4 and Fe2O3 surfaces using the Materials Studio.Previous studies have focused on the inhibition effect of scale inhibitors on CaCO3O4 and Fe2O3 surfaces were calculated using DFT and the results indicated that the adsorption energy difference between the inhibitors and the surface are attributed to differences in quantity and Mulliken population value of chemical bonds.The adsorption energies between the scale inhibitor and the surface were calculated and the results indicated that differences in the effects of the scale inhibitor in the scale inhibition process are attributed to the differences in the adsorption energy of the scale inhibitor molecules adsorbed on the surface. Finally, the number of chemical bonds and the Mulliken population values of inhibitor bonds with the Fe3 cubes, immersed in ultra-pure water (UP water) at 51 °C (the station sewage temperature) for several days until the surfaces were completely/mostly black (Fe3O4) or orange (Fe2O3), and then dried.The No. 20 carbon steel used in this study  was cut into 50 × 25 × 2 mm2 and NaHCO3  were purchased from Sichuan Kelong Company. Each group involved 0.933 g CaCl2 and 0.959 g NaHCO3 . The concentrations of Ca2+ and HCO3− were obtained from water quality testing of the sewage in the station pipe.The CaClThe concentrations of PAA, HPMA, PESA and PASP were 50% and purchased from Shandong Kerry Company. Each scale inhibitor was diluted to 1 g/L. Experimentally, 10 mL inhibitor solution was poured into the solution so that the concentration of the scale inhibitor in the test solution was 10 mg/L.2 and NaHCO3 were added to generate CaCO3.UP water was added to a beaker with an additional 30 mL UP water to compensate for evaporation loss . The water was heated to 51 °C on a stirring hotplate; CaCl2, NaHCO3 and scale inhibitor added in each group were:2 + NaHCO3 + 1 L UP water;CaCl2 + NaHCO3 + 0.99 L UP water + 10 mL PAA;CaCl2 + NaHCO3 + 0.99 L UP water + 10 mL HPMA;CaCl2 + NaHCO3 + 0.99 L UP water + 10 mL PESA;CaCl2 + NaHCO3 + 0.99 L UP water + 10 mL PASP;CaClThe quantities of CaCl2 and NaHCO3 addition; a hanging piece of carbon steel (size 5 × 3) was added to the beaker 30 min after the addition of the scale inhibitor. The experiment lasted for 24 h. After 24 h, the hanging pieces were dried and purged. Trials involving hanging pieces of both Fe3O4 and Fe2O3 were repeated three times for each surface. The experimental set-up is shown in Fig. For Groups 2–5, the scale inhibitor was added 30 min after CaCl15. The Castep module was used to calculate the bond number and the Mulliken population value between the scale inhibitor molecule and the surface, and its functionality is GGA and PBE17.In this study, the Amorphous Cell, Discover, Forcite, and Caste modules in Materials Studio 7.0 software were used. The Amorphous Cell module was used to create a mixed layer of water molecules and scale inhibitor molecules. The Discover module was used to minimize energy while the Forcite module was used to run molecular dynamics simulation programs using the COMPASS force field20 of Fe3O4 crystals and the (104) surface of Fe2O3 crystals were examined as adsorption surfaces23. The initial molecular models of the Fe3O4 and Fe2O3 crystals were imported from a software database; the designated surface was cut to obtain the required adsorption surface. The a, b and c values of the (111) surface model of the established Fe3O4 crystal were 10.28 Å, 11.87 Å and 42.53 Å, respectively; the a, b and c values of the (104) surface model of the Fe2O3 crystal were 7.41 Å, 10.08 Å and 42.7 Å, respectively. All atoms on the surface were set in a fixed state. The surface model established is shown in Fig. In this study, the (111) surface24. The initial adsorption models of all inhibitors on both surfaces are shown in Fig. The four scale inhibitor molecules were manually drawn see Fig. . Since a−7. The Forcite module was used for molecular dynamics simulation. The NVT ensemble was used, the temperature was 324 K , the number of steps calculated was 20,000,000 and Berendsen was selected as Themostat. The adsorption models of the scale inhibitor molecule on the (111) surface of Fe3O4 and the (104) surface of Fe2O3 from molecular dynamics calculations are shown in Fig. After establishing the initial adsorption models, the energy was minimized using the discover module. Smart minimizer, which includes Steepest descent, Conjugate gradient and Newton, was selected as the energy minimization method in the module. The convergence of all methods was set at 10 K i.e., 1 °C, the2 dimension were selected and simultaneously detected by SEM  and EDS (magnification 1500x). The SEM images of Fe3O4 and Fe2O3 steel hanging pieces are shown in Figs A single hanging piece was set on a microscope carrier and two random points on the solution surface side of the 50 × 25 mm3 covered almost the entire surface of the hanging piece in the absence of scale inhibitors, while a large number of “ditches” and “holes” were observed in the presence of scale inhibitors, indicating a reduced CaCO3 surface coverage.As shown in Figs The mass ratios and quantitative ratios of Ca and Fe on the detection points of the hanging pieces were obtained by EDS and are shown in Tables Tables 3 increased and the scale inhibition effect degraded as the Ca/Fe ratio increased. As shown in Table Since the areas of all detection points are identical, the area occupied by CaCO3O4 increase in the following manner PESA < PAA < PASP < HPMA, indicating that inhibition of CaCO3 scale on the Fe3O4 surface follows the same sequence. The Ca/Fe ratios of the four scale inhibitors on the surface of Fe2O3 follow the sequence of PESA < PASP < HPMA < PAA.In addition, the Ca/Fe ratios are different for different inhibitors. Indeed, the Ca/Fe ratios of the four inhibitors on the surface of Fe3 surface adsorption by scale inhibitors is that active sites on the surface prefer occupation by the inhibitor molecules relative to CaCO3. The adsorption energy between the inhibitor molecules and the surface is calculated by26:Esurf and Einhi refer to the model energy in the presence of surface or scale inhibitor molecules, respectively. The adsorption energies between the four inhibitor molecules and the surfaces are shown in Table The inhibition of CaCOE values in Table E follows the sequence of PESA < PAA < PASP < HPMA, indicating the adsorption strength of the inhibitors on the Fe3O4 surface increases PESA > PAA > PASP > HPMA. For Fe2O3, the ΔE increased in the following manner, PESA < PASP < HPMA < PAA which means the inhibitor adsorption strength on the Fe2O3 surface decreased in the following manner PESA > PASP > HPMA > PAA. As the adsorption strength increased, the stability of adsorption of the inhibitor on the surface increased. As a result, active sites on the surface are not easily occupied by CaCO3, enhancing scale inhibition. Therefore, the adsorption effects of the four inhibitors on the surfaces of Fe3O4 and Fe2O3 depend on the adsorption energy between the inhibitor and the surface.All Δ3O4 and inhibitors PASP and PAA were similar, as were the Ca/Fe ratios and inhibition effects. For the Fe2O3 surface, the PSAP and PESA adsorption energies were significantly lower than the adsorption energies of HPMA and PAA so the inhibitory effects and Ca/Fe ratios of PSAP and PESA were markedly lower for the Fe2O3 surface.As shown in Tables As the bonds between the inhibitor molecule and the surface increased and the bonding Mulliken population value increased, the binding affinity of the scale inhibitor molecule and the surface increased so the adsorption energy decreased. Therefore, the difference in adsorption energy between the inhibitor and the surface can be attributed to the number of bonds between the inhibitor molecule and the surface as well as the bonding Mulliken population value. The bonding between each inhibitor and the surfaces is shown in Table As shown in Table 3O4 surface, three H-O bonds formed between PESA and Fe3O4 with Mulliken population values >0.1. Indeed, PESA was superior to the other three samples in terms of both the total number of H-O bonds and bonds with Mulliken population values >0.1. Hence, the adsorption strength of PESA on the Fe3O4 surface was the highest among all samples. PSAP and PAA each formed two H-O bonds with Fe3O4 and both had one bond with a Mulliken population value <0.1. Therefore, the adsorption of PAA and PASP on Fe3O4 surface was slightly weaker than PESA. The Mulliken population values of the two H-O bonds between PAA and Fe3O4 were slightly higher than the two H-O bonds between PASP and Fe3O4; therefore, the adsorption strength of PAA on Fe3O4 was slightly higher than PASP. However, only one H–O bond was generated between HPMA and Fe3O4 and its Mulliken population value was below 0.1. Hence, the adsorption strength of HPMA on Fe3O4 was the lowest among all inhibitor molecules. In summary, the adsorption strengths of scale inhibitors on Fe3O4 surface follow the sequence of PESA > PAA > PASP > HPMA, which is consistent with the sequence of adsorption energy.Upon inhibitor adsorption on the Fe2O3, 6 H-O bonds were generated between PESA and Fe2O3; four of them had Mulliken population values above 0.1. Indeed, PESA was superior to the other three samples in terms of both the total number of H-O bonds and bonds with Mulliken population values >0.1. Hence, the adsorption strength of PESA on Fe2O3 surface was the highest among all samples. PASP and Fe2O3 formed 3 H-O bonds and two of them had Mulliken population values above 0.1. Two H-O bonds were generated between HPMA and Fe2O3, and one of them had a Mulliken population value above 0.1. Therefore, the adsorption strength of PASP on Fe2O3 was lower than PESA, but higher than HPMA. As only one H-O bond was generated between PAA and Fe2O3, the adsorption strength of PAA on Fe2O3 was the lowest among all samples.Upon adsorption onto FeThe adsorption energy between scale inhibitors and the surfaces clearly depends on the number of H-O bonds generated between the inhibitor, the surface and their Mulliken population values.3 to the surfaces of Fe3O4 and Fe2O3. According to average Ca/Fe ratios obtained by EDS, the scale inhibition effect follows the sequence of PESA > PAA > PASP > HPMA and PESA > PASP > HPMA > PAA for Fe3O4 and Fe2O3 surfaces, respectively. The adsorption energies between the inhibitor molecules and the surface were calculated by molecular dynamics simulations. The sequence of adsorption energies is PESA < PAA < PASP < HPMA and PESA < PASP < HPMA < PAA for Fe3O4 and Fe2O3 surfaces, respectively. A low adsorption energy means strong inhibitor adsorption on the surface and inhibition depends on adsorption strength. Thus, these results demonstrated that excellent inhibition is due to low adsorption energy between the scale inhibitor and the surface. The number of bonds generated and their Mulliken population values calculated by DFT indicated that low adsorption energy depends on the formation of considerable H-O bonds with high Mulliken population values between the scale inhibitor and the surface.This study presents a study of the inhibitory effects of PAA, HPMA, PESA and PASP on the adsorption of CaCO


In addition to their microstructures, the microwave absorption properties of such spheres were investigated. The results show that the grain size and hollowness of Fe3O4 hollow spheres both increase as the reaction time increases. With increasing hollowness, the attenuation ability of electromagnetic wave of Fe3O4 spheres increases first and then decreases, finally increases sharply after the spheres break down. Samples with strong attenuation ability can achieve good impedance matching, which it does preferentially as the absorber thickness increases. Fe3O4 hollow spheres show the best microwave absorption performance when the reaction time is 24 h. The minimum reflection loss (RL(min)) can reach −40 dB, while the thickness is only 3.2 mm.Hollow magnetic structures have great potential to be used in the microwave absorbing field. Herein, Fe This stable and excellent magnetic property has attracted many scholars’ attention. However, the high density of Fe3O4 limits its further use as a MAM [It is well known that the structure of materials plays an important role in their thermo-mechanical behavior and transport properties. Hollow structures have shown great application prospects in lithium batteries, super capacitors, drug transport, biomedicine, gas sensors and other fields due to their advantages of large specific surface area and low density ,3,4,5,6.as a MAM . 3O4 is an effective way to reduce material weight, produce special morphological effects and improve electromagnetic properties [3O4 spheres with a diameter of 450 nm, a wall thickness of 80 nm and a density of 3.28 g/cm3 by solvothermal method, which was nearly 27% lower than the corresponding solid Fe3O4. Sui et al. [3O4 hollow spheres, and synthesized hollow spheres with diameters of 200–1000 nm and wall thicknesses of 35–280 nm. Xu et al. [3O4 spheres with a diameter of 525 nm by thermal solvent method. When the filling mass is 60% and the thickness is 3 mm, the minimum reflection loss can reach −15.8 dB. The above research shows that the Fe3O4 hollow spheres with low density have very good application prospects in the field of microwave absorption, and that it is feasible to adjust the electromagnetic characteristics of Fe3O4 hollow spheres by morphology control. However, the relationship between the morphology of Fe3O4 hollow spheres and the microwave absorption characteristics remains to be further studied. Fortunately, many studies have shown that hollowing of Feoperties ,18,19. Foperties  preparedi et al.  used theu et al.  prepared3O4 hollow spheres with different levels of hollowness were prepared by Ostwald ripening mechanism. The variation of the morphology of Fe3O4 hollow spheres under the Ostwald ripening mechanism was studied. The relationships among solvothermal reaction time, structure of Fe3O4 hollow spheres and electromagnetic properties were discussed. In the present work, Fe3O4 was carried out as follows: 10 g Polyvinylpyrrolidone (PVP), 9 g FeCl3·6H2O and 36 g urea were dissolved in 400 mL ethylene glycol, and stirred for 0.5 h by electric mixer to get a deep orange transparent homogenous solution. Then, they were put into a 500 mL stainless-steel autoclave with teflon-lining, and kept at 200 °C for 8 h, 12 h, 16 h, 20 h and 24 h, respectively. After the reaction, all the reaction products were washed with water and alcohol for three times to remove the unreacted. Finally, the reaction products were collected by a magnet and dried in vacuum at 60 °C for 10 h. The code numbers of the sample at 8 h, 12 h, 16 h, 20 h and 24 h were marked as S1, S2, S3, S4 and S5, respectively.A typical preparation of hollow Fe3O4 hollow microspheres were analyzed by a field emission scanning electron microscope , transmission electron microscopy , and X-ray diffractometer  using a CuKa radiation (λ = 1.5406 Å). The magnetostatic properties were characterized by vibrating sample magnetometer . The permeability and permittivity of samples in the frequency range 2–18 GHz were tested by a vector network analyzer  for simulation of reflection loss. Composite sample were realized as follows: the wax was melted at 80 °C and mixed with the Fe3O4 powder homogeneously. The mixture was moved into a toroidal mold . The test software  is 85071 and the calibration part is 85050D. Before the test, the permittivity of air was measured as an evaluation of calibration effect. The morphology and structure of Fe3O4 with different reaction times are shown in 3O4 (JCPDS Card No. 99-0073), which indicates that the synthesized products have high purity. The diffraction peak intensities increase obviously as the reaction time increases. This means that the samples’ crystallinity is improved as the reaction time increases. According to the calculation results of the Scherrer formula (D = Kγ/Bcosθ), the grain size of the sample at 8 h, 12 h, 16 h, 20 h and 24 h is 25.89 nm, 30.54 nm, 38.28 nm, 41.55 nm and 48.29 nm, respectively. The results show that the grain size increases as the reaction time increases. To further identify the purity of Fe3O4, RedOx tiration (potassium dichromate) was used. 2+):n(Fe3+), FeσO4 (σ-nonstoichiometric) and Oxidation rate, respectively. Although Fe3O4 may be oxidized during the experiment, the results in 3O4 phase in the product is very high. XRD results of Fe3O4 spheres exhibit good dispersion and no agglomeration. As shown in the SEM images from 3O4 sphere is composed of many Fe3O4 grains, which shows the self-assembly effect of Ostwald ripening mechanism. Similar results can be seen from the TEM images, 3O4 sphere increases gradually as the reaction time increases. The hollow size of Fe3O4 increases to breaking point as the reaction time reaches 24 h (S5). It is worth mentioning that although the formation of Fe3O4 hollow spheres reflects the typical Ostwald ripening phenomenon, the size of Fe3O4 spheres does not increase significantly during the whole reaction process. As can be seen from 3O4 hollow spheres are mainly around 500 nm before they are broken. This may be due to the higher PVP concentration, which restricts the growth of Fe3O4 spheres during Ostwald ripening process [To observe the morphology and internal structure of the samples, SEM and TEM analyses were carried out, and the results are illustrated in  process .3O4 in this study can be explained as shown in 3O4 spheres, as illustrated in 3O4 spheres with hollow structure. In addition, there is residual stress in the external grains due to the continuous growth of Fe3O4 grains and the restraint of high PVP concentration. Excessive residual stress leads to the cracks at grain boundaries, resulting in crystal rupture, and the rupture of Fe3O4 spheres ultimately, as shown in Based on the results of SEM and TEM images, the formation process of Fe3O4 samples at different reaction time. The saturation magnetization and coercivity of Fe3O4 samples are shown in 3O4 has a significant effect on its magnetic properties. As the reaction time is prolonged, the defects of the sample decrease, the crystallinity is improved, and the super-exchange effect of the Fe–O–Fe bond is enhanced, resulting in a higher saturation magnetization [3O4 is woken up as the reaction time is in the range of 12–24 h, which may be due to the hollow structure reducing the magnetic coupling between the Fe3O4 grains. The hollow structure may have a certain strengthening effect on the coercive force of Fe3O4, which is manifested in the increase in the coercive force of the Fe3O4 sphere at higher hollowness, and which suddenly decreases when the hollow sphere is broken. The report [3O4 nanoparticles is 25 nm. Fe3O4 grains prepared in this paper are generally larger than this value, thus showing so it shows ferromagnetism. tization . Howevere report  shows thεr = ε′ − jε″), dielectric loss tangent and Cole-Cole semicircle of samples in the range of 2–18 GHz are illustrated in 3O4 hollow spheres with different morphologies varies significantly with the increase of reaction time. The variation ranges of real and imaginary parts of complex permittivity are 6.1–11.8 and 0.2–1.5, respectively. The dielectric properties of different samples vary greatly and show no obvious regularity, which is related to the complex variation of polarization and conductivity affected by the grain size of Fe3O4 and the state of dispersion and aggregation. The frequency dependence of complex permittivity (δE = ε″/ε′) reflects the dielectric loss ability of material. Tan δE of Fe3O4 samples at different time are shown in δE is similar to ε″. Tan δE decreases with the prolongation of reaction time (S1–S3) before the rupture of Fe3O4 spheres, and increases slightly as the reaction time reaches 20 h (S4). There are two obvious loss peaks in tan δE curve with frequency after the rupture of Fe3O4 spheres (S5), at 10.86 GHz and 16.82 GHz, respectively. The appearance of the loss peak increases the dielectric loss capacity of S5 at this frequency greatly. According to Debye relaxation theory, the real and imaginary parts of complex permittivity can be transformed into the following form [The dielectric loss tangent (tan ing form :(1)εr=ε∞f is the frequency, ε∞ and εs are relative dielectric permittivity at the high-frequency limit and static dielectric permittivity, respectively, and τ is the relaxation time. Therefore, ε′ and ε″ can be further transformed: In Formula (1), ε′ and ε″ can be further deduced:According to Formulas (2) and (3), the relationship between ε″ = (εs − ε∞)/2 when 2πf = τ−1. However, the ε′ of S5 is maintained at about 10 initially, then decreases to 8.9 from 10.3 to 11.4 GHz, resulting in a value that corresponds to a loss peak of ε″ (10.86 GHz). Simply estimated, the maximum value of the loss peak is much larger than that of (εs − ε∞)/2, indicating that the dielectric behavior is not a typical Debye relaxation. This behavior may correspond to a resonance process similar to dielectric relaxation. Overall, we consider that the dielectric loss of Fe3O4 is not Debye relaxation, but resonant dielectric response.According to Formula (4). If the polarization of the permittivity is caused by Debye relaxation process, it will be shown as a Cole-Cole semicircle. Based on the above theory, 3D illustration of Cole-Cole curves is made as shown in μr = μ′ − jμ″), magnetic loss tangent and C0 of samples in the range of 2–18 GHz. From μ′) and imaginary part of permeability (μ″) curves exhibit a similar trend, decreasing first and then remaining stable. This indicates that the magnetic loss ability of Fe3O4 is mainly reflected in the S band (2–4 GHz) and C band (4–8 GHz), and Ostwald ripening has less effect on the magnetic properties than on the dielectric properties of Fe3O4. Similarly to dielectric loss, the magnetic loss tangent (tan δM = μ″/μ′) reflects the magnetic loss ability of materials, and tan δM can also be observed in δM, at which is much larger than that of tan δE. Tan δM decreases slowly and finally approaches to tan δE as the frequency increases. Therefore, it can be judged that the loss mechanism of Fe3O4 is mainly magnetic loss. For ferrite materials, magnetic loss is usually caused by hysteresis loss, eddy current loss, domain wall displacement and natural resonance. However, hysteresis loss can be neglected in the case of weak applied electric field, and domain wall displacement only occurs in the MHz range, so the magnetic loss mechanism in Fe3O4 is generally related to eddy current loss and natural resonance. Material thickness (d) and conductivity (σ) are two main factors affecting eddy current loss, which can be expressed as follows [ follows :(5)C0=μ″C0 with frequency should be revealed in a constant. In other words, the eddy current loss should be dominant in the frequency range of relatively stable and small fluctuations. As shown in C0 curves of Fe3O4 fluctuate greatly at low frequencies and tend to be stable at the middle and high frequencies, indicating that the magnetic loss should be caused by natural resonance at low frequency, and as the frequency increases, it gradually changes into eddy current loss. Combined with 3O4 [C0 approaches zero at the middle and high frequencies, indicating that the eddy current loss is very weak. This is consistent with the weak magnetic loss at the corresponding frequency in 3O4 is about 10 nm [3O4 hollow spheres; there are some grains about 10 nm in size, so the speculation of exchange resonance in S1 is valid.If the magnetic loss is caused entirely by the eddy current loss, the right side of Equation (5) is constant, so no the variation of with 3O4 . In addiut 10 nm . In addiThe energy of the electromagnetic wave is transferred to heat energy by dielectric loss and magnetic loss as the electromagnetic wave enters into the absorber. The attenuation constant α determines the capability attenuation characteristics of materials to attenuate the electromagnetic wave, which can be expressed by the following formula ,31,32;, and increases after the sphere ruptures at 24 h (S5). To study the attenuation ability of different samples in each work frequency bands, the integral values of α in each band are calculated. The specific results are shown in In Formula (6), RL) of Fe3O4 can be deduced from the transmission line theory [On the basis of the complex permittivity and complex permeability data, the reflection loss (e theory :(7)RL=20Zin stands for the input impedance of absorbing material, Z0 is the impedance of free space, c is the speed of light in vacuum, d is the thickness of absorber, and f represents microwave frequency. Based on the above formulas, RL can be simulated as the thickness is in the range of 0–10 mm and the frequency is 2–18 GHz, as depicted in f = c/2πdμ″, where f represents the optimal matching frequency, d is the optimal matching thickness. Therefore, the absorption band can be adjusted by changing the thickness of Fe3O4 to meet the actual needs. Moreover, when the thickness of the sample exceeds a certain value , there are absorption peaks at both low and high frequencies, which indicates that Fe3O4 is promising as a low frequency and high frequency compatible microwave absorbing material. In addition, RL is very sensitive to the change of thickness and can produce very strong reflection loss at a specific thickness. That can be explained by a quarter-wavelength model [Among them, th model :(9)tm=ncεr| and |μr| are the modulus of εr and μr at fm, respectively. If the thickness of the absorber is equal to the calculated tm, the interference effect will occur, and the electromagnetic wave will be attenuated greatly. When n = 1, 3 and 5, the frequency dependence of tm is calculated and plotted on the contour maps of S1–S5 in RL (min) on the curves of tm. Thus, we can judge that the absorption peaks of Fe3O4 samples are aroused by thickness resonance to the specific frequency microwave.Where |RL at resonance thickness are shown in RL (min) of each sample can approach −40 dB, which is equivalent to 99.99% of the electromagnetic wave energy absorbed, indicating that Fe3O4 possesses great potential as an excellent low-frequency microwave absorption material. The normalized characteristic impedance Z is a key parameter in reducing the reflection of the electromagnetic wave, which can be expressed by the following equation [As the thickness of the sample increases, the resonance thicknesses are satisfied, with the quarter-wavelength model appearing in turn, which are 3.2 mm—S5, 3.6 mm—S3, 3.7 mm—S2, 5.2 mm—S1 and 5.4 mm—S4, respectively. The order is consistent with the order of attenuation ability mentioned above and the equation :(10)Z=ZiZin should be equal to the free space impedance Z0, so that the electromagnetic wave can enter into the absorber completely and can be totally attenuated completely; thus, Z should be as close as possible to 1. As shown in 3O4 hollow spheres can be achieved in a thinner case when the attenuation ability is strong.Input impedance 3O4 hollow spheres were fabricated with different reaction times by Ostwald ripening process. The microstructure and electromagnetic properties have been investigated systemically. Fe3O4 spheres all have hollow structure at different reaction times ranging from 8 h to 24 h, the size of Fe3O4 spheres remains at about 500 nm in diameter. The grain size and hollowness of Fe3O4 spheres increase as the reaction time. Fe3O4 hollow spheres break down as the reaction time reaches 24 h. With increasing in hollowness, the electromagnetic wave attenuation ability of Fe3O4 spheres increases first and then decreases, and increases sharply after the spheres finally break down. There is an obvious effect on the dielectric and magnetic properties of Fe3O4 spheres with different morphologies, resulting in a significant difference in the attenuation ability of different samples to electromagnetic waves. The electromagnetic attenuation ability of Fe3O4 spheres is S5 > S3 > S2 > S1 > S4. Sample with strong attenuation ability can achieve impedance matching preferentially with an increase in thickness. In addition, Fe3O4 hollow nanospheres exhibit good microwave absorption properties due to the strong natural resonance loss and interference cancellation of electromagnetic wave. RL (min) can reach −40 dB as the thickness is only 3.2 mm and the reaction time is 24 h.Fe