Unravelling the effect of paramagnetic Ni2+ on the 13C NMR shift tensor for carbonate in Mg2-xNixAl layered double hydroxides by quantum-chemical computations.

Structural disorder and low crystallinity render it challenging to characterise the atomic-level structure of layered double hydroxides (LDH). We report a novel multi-step, first-principles computational workflow for the analysis of paramagnetic solid-state NMR of complex inorganic systems such as LDH, which are commonly used as catalysts and energy storage materials. A series of 13CO32--labelled Mg2-xNixAl-LDH, x ranging from 0 (Mg2Al-LDH) to 2 (Ni2Al-LDH), features three distinct eigenvalues δ11, δ22 and δ33 of the experimental 13C chemical shift tensor. The δii correlate directly with the concentration of the paramagnetic Ni2+ and span a range of |δ11 - δ33| ≈ 90 ppm at x = 0, increasing to 950 ppm at x = 2. In contrast, the isotropic shift, δiso(13C), only varies by -14 ppm in the series. Detailed insight is obtained by computing (1) the orbital shielding by periodic density-functional theory involving interlayer water, (2) the long-range pseudocontact contribution of the randomly distributed Ni2+ ions in the cation layers (characterised by an ab initio susceptibility tensor) by a lattice sum, and (3) the close-range hyperfine terms using a full first-principles shielding machinery. A pseudohydrogen-terminated two-layer cluster model is used to compute (3), particularly the contact terms. Due to negative spin density contribution at the 13C site arising from the close-by Ni2+ sites, this step is necessary to reach a semiquantitative agreement with experiment. These findings influence future NMR investigations of the formally closed-shell interlayer species within LDH, such as the anions or water. Furthermore, the workflow is applicable to a variety of complex materials.

The magnetic properties of MAl4(OH)12SO4·3H2O with M = Co2+, Ni2+, and Cu2+ determined by a combined experimental and computational approach.

The magnetic properties of the nickelalumite-type layered double hydroxides (LDH), MAl4(OH)12(SO4)·3H2O (MAl4-LDH) with M = Co2+ (S = 3/2), Ni2+ (S = 1), or Cu2+ (S = 1/2) were determined by a combined experimental and computational approach. They represent three new inorganic, low-dimensional magnetic systems with a defect-free, structurally ordered magnetic lattice. They exhibit no sign of magnetic ordering down to 2 K in contrast to conventional hydrotalcite LDH. Detailed insight into the complex interplay between the choice of magnetic ion (M2+) and magnetic properties was obtained by a combination of magnetic susceptibility, heat capacity, neutron scattering, solid-state NMR spectroscopy, and first-principles calculations. The NiAl4- and especially CoAl4-LDH have pronounced zero-field splitting (ZFS, easy-axis and easy-plane, respectively) and weak ferromagnetic nearest-neighbour interactions. Thus, they are rare examples of predominantly zero-dimensional spin systems in dense, inorganic matrices. In contrast, CuAl4-LDH (S = 1/2) consists of weakly ferromagnetic S = 1/2 spin chains. For all three MAl4-LDH, good agreement is found between the experimental magnetic parameters (J, D, g) and first-principles quantum chemical calculations, which also predict that the interchain couplings are extremely weak (< 0.1 cm-1). Thus, our approach will be valuable for evaluation and prediction of magnetic properties in other inorganic materials.

Variation in Phosphorus Speciation of Sewage Sludge throughout Three Wastewater Treatment Plants: Determined by Sequential Extraction Combined with Microscopy, NMR Spectroscopy, and Powder X-ray Diffraction.

The variation in phosphorus (P) speciation of sewage sludge throughout three wastewater treatment plants (WWTPs) was obtained by combining sequential P extraction with optical and scanning electron microscopy (SEM), chemical analyses, powder X-ray diffraction (PXRD), and 27Al and 31P nuclear magnetic resonance (NMR) spectroscopy. The WWTPs combine chemical P removal (CPR) and enhanced biological P removal (EBPR) and were compared to understand the effect of iron (Fe) dosing with and without codosing of aluminum (Al) and thermal hydrolysis on the P speciation. 31P NMR showed comparable inorganic orthophosphate (ortho-P, 53-60% of total P) and organophosphate (organic-P, 37-45%) in primary sludge, whereas polyphosphate (poly-P, 23-44%) from poly-P accumulating organisms (PAOs) was mainly observed in the secondary sludge. Inorganic ortho-P (90-98%) dominated after anaerobic digestion, which degraded poly-P and most organic-P. The inorganic ortho-P was mainly Fe bound P (Fe-P), especially after anaerobic digestion (71%). Codosing of Fe and Al led to two comparable fractions: Fe-P (38%) and P sorbed on amorphous Al (hydr)oxides (38%). Vivianite was identified in all samples by microscopy and chemical extraction but was PXRD amorphous in 12 out of 17 samples. Thus, vivianite may be more common in sewage sludge than previously known.

Quantification of Biologically and Chemically Bound Phosphorus in Activated Sludge from Full-Scale Plants with Biological P-Removal.

Phosphorus (P) is present in activated sludge from wastewater treatment plants in the form of metal salt precipitates, extracellular polymeric substances, or bound into the biomass, for example, as intracellular polyphosphate (poly-P). Several methods for a reliable quantification of the different P-fractions have recently been developed, and this study combines them to obtain a comprehensive P mass-balance of activated sludge from four enhanced biological phosphate removal (EBPR) plants. Chemical characterization by ICP-OES and sequential P fractionation showed that chemically bound P constituted 38-69% of total P, most likely in the form of Fe, Mg, or Al minerals. Raman microspectroscopy, solution state 31P NMR, and 31P MAS NMR spectroscopy applied before and after anaerobic P-release experiments, were used to quantify poly-P, which constituted 22-54% of total P and was found in approximately 25% of all bacterial cells. Raman microspectroscopy in combination with fluorescence in situ hybridization was used to quantify poly-P in known polyphosphate-accumulating organisms (PAO) (Tetrasphaera, Candidatus Accumulibacter, and Dechloromonas) and other microorganisms known to possess high level of poly-P, such as the filamentous Ca. Microthrix. Interestingly, only 1-13% of total P was stored by unidentified PAO, highlighting that most PAOs in the full-scale EBPR plants investigated are known.

Synthesis and Thermal Degradation of MAl4(OH)12SO4·3H2O with M = Co2+, Ni2+, Cu2+, and Zn2.

The synthesis and thermal degradation of MAl4(OH)12SO4·3H2O layered double hydroxides with M = Co2+, Ni2+, Cu2+, and Zn2+ ("MAl4-LDH") were investigated by inductively coupled plasma-optical emission spectroscopy, thermogravimetric analysis, powder X-ray diffraction, Rietveld refinement, scanning electron microscopy, scanning tunnel electron microscopy, energy-dispersive X-ray spectroscopy, and solid-state 1H and 27Al NMR spectroscopy. Following extensive synthesis optimization, phase pure CoAl4- and NiAl4-LDH were obtained, whereas 10-12% unreacted bayerite (Al(OH)3) remained for the CuAl4-LDH. The optimum synthesis conditions are hydrothermal treatment at 120 °C for 14 days (NiAl4-LDH only 9 days) with MSO4(aq) concentrations of 1.4-2.8, 0.7-0.8, and 0.08 M for the CoAl4-, NiAl4-, and CuAl4-LDH, respectively. A pH ≈ 2 for the metal sulfate solutions is required to prevent the formation of byproducts, which were Ni(OH)2 and Cu3(SO4)(OH)4 for NiAl4- and CuAl4-LDH, respectively. The thermal degradation of the three MAl4-LDH and ZnAl4-LDH in a nitrogen atmosphere proceeds in three steps: (i) dehydration and dehydroxylation between 200 and 600 °C, (ii) loss of sulfate between 600 and 900 °C, and (iii) formation of the end products at 900-1200 °C. For CoAl4-LDH (ZnAl4-LDH), these are α-Al2O3 and CoAl2O4 (ZnAl2O4) spinel. For NiAl4-LDH, a spinel-like NiAl4O7 phase forms, whereas CuAl4-LDH degrades by a redox reaction yielding a diamagnetic CuAlO2 (delafossite structure) and α-Al2O3.

Remarkable reversal of 13C-NMR assignment in d1, d2 compared to d8, d9 acetylacetonate complexes: analysis and explanation based on solid-state MAS NMR and computations.

13C solid-state MAS NMR spectra of a series of paramagnetic metal acetylacetonate complexes; [VO(acac)2] (d1, S = ½), [V(acac)3] (d2, S = 1), [Ni(acac)2(H2O)2] (d8, S = 1), and [Cu(acac)2] (d9, S = ½), were assigned using modern NMR shielding calculations. This provided a reliable assignment of the chemical shifts and a qualitative insight into the hyperfine couplings. Our results show a reversal of the isotropic 13C shifts, δiso(13C), for CH3 and CO between the d1 and d2versus the d8 and d9 acetylacetonate complexes. The CH3 shifts change from about -150 ppm (d1,2) to roughly 1000 ppm (d8,9), whereas the CO shifts decrease from 800 ppm to about 150 ppm for d1,2 and d8,9, respectively. This was rationalized by comparison of total spin-density plots and computed contact couplings to those corresponding to singly occupied molecular orbitals (SOMOs). This revealed the interplay between spin delocalization of the SOMOs and spin polarization of the lower-energy MOs, influenced by both the molecular symmetry and the d-electron configuration. A large positive chemical shift results from spin delocalization and spin polarization acting in the same direction, whereas their cancellation corresponds to a small shift. The SOMO(s) for the d8 and d9 complexes are σ-like, implying spin-delocalization on the CH3 and CO groups of the acac ligand, cancelled only for CO by spin polarization. In contrast, the SOMOs of the d1 and d2 systems are π-like and a large CO-shift results from spin polarization, which accounts for the reversed assignment of δiso(13C) for CH3 and CO.

Structural characterization and magnetic properties of chromium jarosite KCr3(OD)6(SO4)2.

Potassium chromium jarosite, KCr3(OH)6(SO4)2 (Cr-jarosite), is considered a promising candidate to display spin liquid behavior due to the strong magnetic frustration imposed by the crystal structure. However, the ground state magnetic properties have been debated, since Cr-jarosite is notoriously non-stoichiometric. Our study reports the magnetic properties for deuterated KCr3(OD)6(SO4)2 on chemically well-defined samples, which have been characteried by a combination of powder X-ray diffraction, neutron diffraction, solid state NMR spectroscopy, and scanning electron microscopy with energy dispersive spectroscopy. Eight polycrystalline samples, which all contained only 1-3% Cr vacancies were obtained. However, significant substitution (2-27%) of potassium with H2O and/or H3O+ was observed and resulted in pronounced stacking disorder along the c-axis. A clear second-order transition to an antiferromagnetically ordered phase at TN = 3.8(1) K with a small net moment of 0.03 µB per Cr3+-ion was obtained from vibrating sample magnetometry and temperature dependent neutron diffraction. The moment is attributed to spin canting caused by the Dzyaloshinskii-Moriya interaction. Thus, our experimental results imply that even ideal potassium chromium jarosite will exhibit magnetic order below 4 K and therefore it does not qualify as a true spin liquid material.

Applications of solid-state NMR spectroscopy in environmental science.

Environmental science is an interdisciplinary field, which integrates chemical, physical, and biological sciences to study environmental problems and human impact on the environment. This article highlights the use of solid-state NMR spectroscopy (SSNMR) in studies of environmental processes and remediation with examples from both laboratory studies and samples collected in the field. The contemporary topics presented include soil chemistry, environmental remediation (e.g., heavy metals and radionuclides removal, carbon dioxide mineralization), and phosphorus recovery. SSNMR is a powerful technique, which provides atomic-level information about speciation in complex environmental samples as well as the interactions between pollutants and minerals/organic matter on different environmental interfaces. The challenges in the application of SSNMR in environmental science (e.g., measurement of paramagnetic nuclei and low-gamma nuclei) are also discussed, and perspectives are provided for the future research efforts.

Synthesis and Structural Characterization of a Pure ZnAl4(OH)12(SO4)·2.6H2O Layered Double Hydroxide.

The phase purity of a series of ZnAl4(OH)12SO4· nH2O layered double hydroxides (ZnAl4-LDH) obtained from a reaction of bayerite (Al(OH)3) with an excess of zinc(II) sulfate under hydrothermal conditions was investigated as a function of the reaction temperature, the duration of the hydrothermal treatment, and the zinc(II) concentration. The product quality, i.e., crystalline impurities, Al impurities, and bulk Zn:Al ratio, were assessed by powder X-ray diffraction (PXRD), 27Al MAS NMR, and elemental analysis. Structural characterization of a stoichiometric ZnAl4-LDH (120 °C, 9 days, and 2.8 M Zn(II)) showed a well-defined structure of the metal ion layer as evidenced by a single, well-defined Zn environment: i.e., no Zn substitution on the Al sites according to Zn k-edge EXAFS and PXRD. Furthermore, nearly all of the 12 different 1H atoms in the -OH groups and 4 27Al resonances could be assigned using 1H,27Al NMR correlation experiments recorded with ultrafast MAS. The interlayer water content is variable on the basis of thermogravimetric analysis and changes in the 1H MAS NMR spectra with temperature. A composition of ZnAl4(OH)12(SO4)·2.6H2O was obtained from a combination of these techniques and confirmed that ZnAl4-LDH is isostructural with the mineral nickelalumite (NiAl4(OH)12SO4·3H2O).

The distribution of reactive Ni2+ in 2D Mg2-xNixAl-LDH nanohybrid materials determined by solid state 27Al MAS NMR spectroscopy.

Layered double hydroxides (LDHs), especially (doped) with transition metals, as well as nanohybrid and 2D materials derived from these structures, are interesting materials due to their catalytic and electrochemical properties. Their reactivity is determined by the atomic level distribution of the transition metal in the LDH cation layer, which is essential to control the design of LDHs with optimized properties. However, low crystallinity, absence of long range order, and/or isoelectronic ions often prevent atomic level structural characterization. A series of poorly crystalline Mg2-xNixAl-NO3 LDH materials were investigated by ultrafast 27Al MAS NMR spectroscopy to determine the distribution of Ni2+ in these as well as possible superstructures and their miscibility gaps. Four Ni2Al-LDH samples with interlayer distances ranging from 7.6 to 17.5 Šwere prepared to assess the contribution of inter- and intralayer magnetic interactions. The effects of the Ni2+ content and the atomic level distribution of Ni2+ were probed by ultrafast 27Al MAS NMR spectroscopy: the Al distribution can be modeled using a binomial distribution and neither a superstructure was identified for the MgNiAl-LDH sample nor a miscibility gap. The 27Al isotropic shift, δiso(27Al), is a very sensitive probe for a number of neighboring Ni2+ in the first metal ion sphere, but to a smaller degree it is also affected by the intercalated anion (interlayer distance). These results were used for detailed characterization of an exfoliated (2D)-restacked Mg1.83Ni0.17Al-LDH nanohybrid material and a Mg1.83Ni0.17Al-LDH-alginate nanohybrid material, in which 27Al MAS NMR showed how the structure and partial dissolution of the LDHs were retained. In contrast, both powder X-ray diffraction and vibrational spectroscopies (IR and Raman) reflected only the overall change in sample composition.

Assignment of solid-state 13C and 1H NMR spectra of paramagnetic Ni(II) acetylacetonate complexes aided by first-principles computations.

Recent advances in computational methodology allowed for first-principles calculations of the nuclear shielding tensor for a series of paramagnetic nickel(II) acetylacetonate complexes, [Ni(acac)2L2] with L = H2O, D2O, NH3, ND3, and PMe2Ph have provided detailed insight into the origin of the paramagnetic contributions to the total shift tensor. This was employed for the assignment of the solid-state 1,2H and 13C MAS NMR spectra of these compounds. The two major contributions to the isotropic shifts are by orbital (diamagnetic-like) and contact mechanism. The orbital shielding, contact, as well as dipolar terms all contribute to the anisotropic component. The calculations suggest reassignment of the 13C methyl and carbonyl resonances in the acac ligand [Inorg. Chem.53, 2014, 399] leading to isotropic paramagnetic shifts of δ(13C) ≈ 800-1100 ppm and ≈180-300 ppm for 13C for the methyl and carbonyl carbons located three and two bonds away from the paramagnetic Ni(II) ion, respectively. Assignment using three different empirical correlations, i.e., paramagnetic shifts, shift anisotropy, and relaxation (T1) were ambiguous, however the latter two support the computational results. Thus, solid-state NMR spectroscopy in combination with modern quantum-chemical calculations of paramagnetic shifts constitutes a promising tool for structural investigations of metal complexes and materials.

Structural Investigation of Zn(II) Insertion in Bayerite, an Aluminum Hydroxide.

Bayerite was treated under hydrothermal conditions (120, 130, 140, and 150 °C) to prepare a series of layered double hydroxides (LDHs) with an ideal composition of ZnAl4(OH)12(SO4)0.5·nH2O (ZnAl4-LDHs). These products were investigated by both bulk techniques (powder X-ray diffraction (PXRD), transmission electron microscopy, and elemental analysis) and atomic-level techniques ((1)H and (27)Al solid-state NMR, IR, and Raman spectroscopy) to gain a detailed insight into the structure of ZnAl4-LDHs and sample composition. Four structural models (one stoichiometric and three different defect models) were investigated by Rietveld refinement of the PXRD data. These were assessed using the information obtained from other characterization techniques, which favored the ideal (nondefect) structural model for ZnAl4-LDH, as, for example, (27)Al magic-angle spinning NMR showed that excess Al was present as amorphous bayerite (Al(OH)3) and pseudoboehmite (AlOOH). Moreover, no evidence of cation mixing, that is, partial substitution of Zn(II) onto any of four Al sites, was observed. Altogether this study highlights the challenges involved to synthesize pure ZnAl4-LDHs and the necessity to use complementary techniques such as PXRD, elemental analysis, and solid-state NMR for the characterization of the local and extended structure of ZnAl4-LDHs.

A solid state NMR study of layered double hydroxides intercalated with para-amino salicylate, a tuberculosis drug.

Para-amino salicylate (PAS), a tuberculosis drug, was intercalated in three different layered double hydroxides (MgAl, ZnAl, and CaAl-LDH) and the samples were studied by multi-nuclear ((1)H, (13)C, and (27)Al) solid state NMR (SSNMR) spectroscopy in combination with powder X-ray diffraction (PXRD), elemental analysis and IR-spectroscopy to gain insight into the bulk and atomic level structure of these LDHs especially with a view to the purity of the LDH-PAS materials and the concentration of impurities. The intercalations of PAS in MgAl-, ZnAl-, and CaAl-LDH's were confirmed by (13)C SSNMR and PXRD. Moreover, (13)C MAS NMR and infrared spectroscopy show that PAS did not decompose during synthesis. Large amounts (20-41%) of amorphous aluminum impurities were detected in the structure using (27)Al single pulse and 3QMAS NMR spectra, which in combination with (1)H single and double quantum experiments also showed that the M(II):Al ratio was higher than predicted from the bulk metal composition of MgAl-PAS and ZnAl-PAS. Moreover, the first high-resolution (1)H SSNMR spectra of a CaAl LDH is reported and assigned using (1)H single and double quantum experiments in combination with (27)Al{(1)H} HETCOR.

Characterization of phosphate sequestration by a lanthanum modified bentonite clay: a solid-state NMR, EXAFS, and PXRD study.

Phosphate (Pi) sequestration by a lanthanum (La) exchanged clay mineral (La-Bentonite), which is extensively used in chemical lake restoration, was investigated on the molecular level using a combination of (31)P and (139)La solid state NMR spectroscopy (SSNMR), extended X-ray absorption spectroscopy (EXAFS), powder X-ray diffraction (PXRD) and sorption studies. (31)P SSNMR show that all Pi was immobilized as rhabdophane (LaPO4·n H2O, n ≤ 3), which was further supported by (139)La SSNMR and EXAFS. However, PXRD results were ambiguous with respect to rhabdophane and monazite (LaPO4). Adsorption studies showed that at dissolved organic carbon (DOC) concentration above ca. 250 µM the binding capacity was only 50% of the theoretical value or even less. No other La or Pi phases were detected by SSNMR and EXAFS indicating the effect of DOC is kinetic. Moreover, (31)P SSNMR showed that rhabdophane formed upon Pi sequestration is in close proximity to the clay matrix.

Solid state 13C and 2H NMR investigations of paramagnetic [Ni(II)(acac)2L2] complexes.

Nine structurally related paramagnetic acetylacetonato nickel(II) complexes: [Ni(acac)2] and trans-[Ni(acac)2(X)2]nH/D2O, X = H2O, D2O, NH3, MeOH, PMePh2, PMe2Ph, or [dppe]1/2, n = 0 or 1, dppe = 1,2-bis(diphenylphosphino)ethane, as well as cis-[Ni(F6-acac)2(D2O)2], F6-acac = hexafluoroacetylonato, have been characterized by solid state (13)C MAS NMR spectroscopy. (2)H MAS NMR was used to probe the local hydrogen bonding network in [Ni(acac)2(D2O)2]D2O and cis-[Ni(F6-acac)2(D2O)2]. The complexes serve to benchmark the paramagnetic shift, which can be associated with the resonances of atoms of the coordinated ligands. The methine (CH) and methyl (CH3) have characteristic combinations of the isotropic shift (δ) and anisotropy parameters (d, η). The size of the anisotropy (d), which is the sum of the chemical shift anisotropy (CSA) and the paramagnetic electron-nuclei dipolar coupling, is much more descriptive than the isotropic shift. Moreover, the CSA is found to constitute up to one-third of the total anisotropy and should be taken into consideration when (13)C anisotropies are used for structure determination of paramagnetic materials. The (13)C MAS NMR spectra of trans-[Ni(acac)2(PMe2Ph)2], trans-[Ni(acac)2(PMePh2)2], and the noncrystallographically characterized trans-[Ni(acac)2(dppe)]n were assigned using these correlations. The complexes with L = H2O, D2O, NH3, and MeOH can be prepared by a series of solid state desorption and sorption reactions. Crystal structures for trans-[Ni(acac)2(NH3)2] and trans-[Ni(acac)2(PMePh2)2] are reported.

In-depth characterization of phosphate intercalated Mg Al Layered double hydroxides and study of the PO4 release properties.

Slow-release fertilizers (SRFs) form the core of innovative strategies in sustainable agriculture. Layered Double Hydroxides (LDH), known for their high capacity to sequester plant nutrients, especially phosphate, are emerging as promising candidates for SRF synthesis. The phosphate release properties of MgAl LDH (with a targeted Mg/Al ratio of 2.0) intercalated with HPO42- anions were assessed in various aqueous environments. A comprehensive analysis, including in-depth chemical and structural characterizations (ICP-OES, XRD, PDF, 27Al NMR, 31P NMR, FTIR, SEM) of the as-prepared phase unveiled a more intricate composition than anticipated for a pure or ideal Mg2Al-HPO4 LDH, encompassing an excess of intercalated phosphate in conjunction with K+. Beyond the intercalated phosphate, solid state 31P NMR speciation identified multiple HxPO4(-3+x) environments, indicating a portion of the phosphate reacting with intralayer Mg2+ to form K-struvite. Additionally, some phosphates were adsorbed onto the surface of amorphous aluminum hydroxide, a side phase formed during MgAl coprecipitation. The phosphate release demonstrated rapid kinetics, occurring within 6 days. Moreover, the released phosphate increased significantly when reducing the Solid/Liquid (S/L) ratio (58%) and further increasing in the presence of carbonate ions (90%). The released phosphate varied from 12% to 90% under different release conditions, transitioning from water to a 3.33 mM NaHCO3 aqueous solution at a low S/L ratio (from 20 mg LDH per mL to 0.02 mg LDH per mL). The simultaneous release of K+, Mg2+, Al3+ indicated the complete dissolution of the K-struvite and partial dissolution of phosphate intercalated MgAl LDH. These results enhanced our understanding of the mechanism governing phosphate release from MgAl LDH, paving the way for potential phosphate recovery by LDH or for the development of LDH-based SRFs.

Combinational Inhibition of P-Glycoprotein-Mediated Etoposide Transport by Zosuquidar and Polysorbate 20.

P-glycoprotein (P-gp) limits the oral absorption of drug substances. Potent small molecule P-gp inhibitors (e.g., zosuquidar) and nonionic surfactants (e.g., polysorbate 20) inhibit P-gp by proposedly different mechanisms. Therefore, it was hypothesised that a combination of zosuquidar and polysorbate 20 may potentiate inhibition of P-gp-mediated efflux. P-gp inhibition by zosuquidar and polysorbate 20 in combination was assessed in a calcein-AM assay and in a transcellular etoposide permeability study in MDCKII-MDR1 and Caco-2 cells. Furthermore, solutions of etoposide, zosuquidar, and polysorbate 20 were orally administered to Sprague Dawley rats. Zosuquidar elicited a high level of nonspecific adsorption to various labware, which significantly affected the outcomes of the in vitro studies. Still, at certain zosuquidar and polysorbate 20 concentrations, additive P-gp inhibition was observed in vitro. In vivo, however, oral etoposide bioavailability decreased by coadministration of both zosuquidar and polysorbate 20 when compared to coadministration of etoposide with zosuquidar alone. For future formulation development, the present study provided important and novel knowledge about nonspecific zosuquidar adsorption, as well as insights into combinational P-gp inhibition by a third-generation P-gp inhibitor and a P-gp-inhibiting nonionic surfactant.

Increased bioavailability of a P-gp substrate: Co-release of etoposide and zosuquidar from amorphous solid dispersions.

P-glycoprotein (P-gp) inhibitors, like zosuquidar, partly increase oral bioavailability of P-gp substrates, such as etoposide. Here, it was hypothesised that co-release of etoposide and zosuquidar from amorphous solid dispersions (ASDs) may further increase oral etoposide bioavailability. This was envisioned through simultaneous co-release and subsequent spatiotemporal association of etoposide and zosuquidar in the small intestinal lumen. To further achieve this, ASDs of etoposide and zosuquidar in polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) 5, and HPMC 4 k were prepared by freeze-drying. From these ASDs, etoposide release was fastest from PVP, then HPMC 5 and slowest from HPMC 4. Release from PVP and HPMC5 resulted in stable supersaturations of etoposide. In transcellular permeability studies across MDCKII-MDR1 cell monolayers, the accumulated amount of etoposide increased 3.7-4.9-fold from amorphous etoposide or when incorporated into PVP- or HPMC 5-based ASDs, compared to crystalline etoposide. In vivo, the oral bioavailability in Sprague Dawley rats increased from 1.0 to 2.4-3.4 %, when etoposide was administered as amorphous drug or in ASDs. However, when etoposide and zosuquidar were co-administered, the oral bioavailability increased further to 8.2-18 %. Interestingly, a distinct increase in oral etoposide bioavailability to 26 % was observed when etoposide and zosuquidar were co-administration in HPMC5-based ASDs. The supersaturation of etoposide as well as the simultaneous co-release of etoposide and zosuquidar in the small intestinal lumen may explain the observed bioavailability increase. Overall, this study suggested that simultaneous co-release of an amorphous P-gp substrate and inhibitor may be a novel and viable formulation strategy to increase the bioavailability P-gp substrates.

Phosphorus doped cyanobacterial biochar catalyzes efficient persulfate oxidation of the antibiotic norfloxacin.

In this study, cyanobacterial biochars (CBs) enriched/doped with non-metallic elements were prepared by pyrolysis of biomass amended with different N, S, and P containing compounds. Their catalytic reactivity was tested for persulfate oxidation of the antibiotic norfloxacin (NOR). N and S doping failed to improve CB catalytic reactivity, while P doping increased reactivity 5 times compared with un-doped biochar. Biochars produced with organic phosphorus dopants showed the highest reactivity. Post-acid-washing improved catalytic reactivity. In particular, 950 ℃ acid-washed triphenyl-phosphate doped CB showed the largest degradation rate and reached 79% NOR mineralization in 2 h. Main attributes for P-doped CBs high reactivity were large specific surface areas (up to 655 m2/g), high adsorption, high C-P-O content, graphitic P and non-radical degradation pathway (electron transfer). This study demonstrates a new way to reuse waste biomass by producing efficient P-doped metal-free biochars and presents a basic framework for designing carbon-based catalysts for organic pollutant degradation.

Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry.

BACKGROUND AND PURPOSE: With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd3+(aq), can be released in patients if the organic ligand is degraded by the radiation. In this study, T1 relaxation measurements were performed to study the effect of radiation on three GBCAs. MATERIALS AND METHODS: GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100 mM. Measurements were performed on a 500 MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100 Gy. The lower detection limit of Gd3+(aq) was established by estimating the overall measurement uncertainty and comparing to corresponding changes in R1 when replacing chelated Gd3+ with gadolinium nitrate at predefined percentages. RESULTS: The overall measurement uncertainty was estimated to ±0.0053 ms-1, corresponding to Gd3+(aq) detection levels 1%-1.5% or 1-4.5 micro molar at clinical GBCA dosage. No detectable differences in R1 were observed between irradiated and non-irradiated samples for any GBCA. CONCLUSIONS: This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.