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Cellulose esters are used in Food and Drug Administration-approved oral formulations, including in amorphous solid dispersions (ASDs). Some bear substituents with terminal carboxyl moieties (e.g., hydroxypropyl methyl cellulose acetate succinate (HPMCAS)); these ω-carboxy ester substituents enhance interactions with drug molecules in solid and solution phases and enable pH-responsive drug release. However, the synthesis of carboxyl-pendent cellulose esters is challenging, partly due to competing reactions between introduced carboxyl groups and residual hydroxyls on different chains, forming either physically or covalently cross-linked systems. As we explored ring-opening reactions of cyclic anhydrides with cellulose and its esters to prepare polymers designed for high ASD performance, we became concerned upon encountering gelation. Herein, we probe the complexity of such ring-opening reactions in detail, for the first time, utilizing rheometry and solid-state 13 C NMR spectroscopy. Gelation in these ring-opening reactions was caused predominantly by physical interactions, progressing in some cases to covalent cross-links over time.

The molecular structure of hydrochars produced from 13 C-enriched glucose under various conditions has been elucidated based on advanced one- and two-dimensional (2D) 1 H- 13 C and 13 C- 13 C solid-state nuclear magnetic resonance (NMR) with spectral editing. Regardless of synthesis conditions, hydrochars consist mostly of oxygen-substituted arene rings (including diphenols) and furans connected by alkyl linkers rich in ketones. Cross-linking nonprotonated and methyne (C-H) alkyl carbons have been identified through spectrally edited 2D NMR. Alkenes and 'quaternary' C-O are observed only at low synthesis temperature, while some clusters of fused arene rings are generated at high temperature. Hydrochar composition is nearly independent of reaction time in the range from 1 to 5 h. Equilibration of 13 C magnetization within 1 s shows that the materials are homogeneous on the 5-nm scale, refuting core-shell models of hydrochar microspheres. While furan C-O carbons bonded to alkyl groups or ketones show distinctive cross peaks in 2D NMR, phenolic C-OH is observed unambiguously by hydroxyl-proton selection. While methylene-linked furan rings are fairly common, the signal previously assigned to furan Cα-Cα linkages is shown to arise from abundant, stable catecholic ortho-diphenols, whose HO-C=C-OH structure is proved by 2D 13 C- 13 C NMR after hydroxyl-proton selection. Quantitative 13 C NMR spectra of low- and high-temperature hydrochars have been matched by chemical-shift simulations for representative structural models. Mixed phenol and furan rings connected by ketones and alkyl linkers provide good fits of the experimental spectra, while literature models dominated by large clusters of fused rings and with few phenols or alkyl-linked ketones do not., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We introduce donor-acceptor substituted anthracenes as effective molecular solar thermal energy storage compounds that operate exclusively in the solid state. The donor-acceptor anthracenes undergo visible light-induced [4+4] cycloaddition reaction, producing metastable cycloadducts, dianthracenes with quaternary carbons, and storing photon energy. The triggered cycloreversion of dianthracenes to anthracenes discharges the stored energy as heat in the order of 100 kJ/mol (200 J/g). The series of compounds displays remarkable self-heating, or cascading heat release, upon the initial triggering. Such self-activated energy release is enabled by the large energy storage in dianthracenes, low activation energy for their thermal reversion, and effective heat transfer to unreacted molecules in the solid state. This process mirroring the self-ignition of fossil fuels opens up opportunities to use dianthracenes as effective and renewable solid-state fuels that can release energy rapidly and completely upon initial activation., Competing Interests: Declaration of Interests The authors filed a U.S. provisional application related to this work.

While syringyl units are the most abundant monolignols in hardwood lignin, their phenolic (i.e. hydroxyl) end group concentration has not been measured. In two uniformly 13 C-enriched young hardwoods, from beech and oak, the syringyl units were quantitatively investigated by advanced solid-state 13 C NMR. Small signals of OH-terminated syringyl units were resolved in spectrally edited two-dimensional 13 C- 13 C NMR spectra of the two hardwoods. Their distinct peak positions predicted based on literature data were validated via the abundant OH-terminated syringyl units in hydrolyzed 13 C-beechwood. In a two-dimensional 13 C- 13 C exchange spectrum with diagonal-ridge suppression, a well-resolved peak of phenolic syringyl units was observed at the characteristic C-H peak position of syringyl rings, without significant overlap from guaiacyl peaks. Accurate 13 C chemical shifts of regular and end-group syringyl units were obtained. Through spectrally edited 2D NMR after 1 H inversion recovery, phenols of condensed tannin complexed with arginine were carefully analyzed and shown to overlap minimally with signals from phenolic syringyl units. The local structure and resulting spin dynamics of ether (chain) and hydroxyl (end-group) syringyl units are nearly the same, enabling quantification by peak integration or deconvolution, which shows that phenolic syringyl end groups account for 2 ± 1 % of syringyl units in beechwood and 5 ± 2 % in oakwood. The observed low end-group concentration needs to be taken into account in realistic molecular models of hardwood lignin structure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A good explanation of lithium-ion batteries (LIBs) needs to convincingly account for the spontaneous, energy-releasing movement of lithium ions and electrons out of the negative and into the positive electrode, the defining characteristic of working LIBs. We analyze a discharging battery with a two-phase LiFePO 4 /FePO 4 positive electrode (cathode) from a thermodynamic perspective and show that, compared to loosely-bound lithium in the negative electrode (anode), lithium in the ionic positive electrode is more strongly bonded, moves there in an energetically downhill irreversible process, and ends up trapped in the positive electrode. Only a sufficiently high charging voltage can drive it back to the other electrode. Since the stronger bonding in the positive electrode lowers the energy by ∼320 kJ mol -1 , a lot of energy is released. This explanation is quantitatively supported by an analysis of cohesive-energy differences of the electrode materials. Since electrons are only intermediates in the discharge reaction and the chemical potential of the electron cannot be measured, electrons do not need to be assigned a distinct energetic role. The incorporation of Li + and an electron into the cathode is accompanied by the reduction of another ion or atom, usually a transition metal such as Fe or Co. The metal's ionization energy in the corresponding oxidation step correlates with the cell voltage, based on a decomposition of cohesive energy into electronic and ionic components. We relate the differences in cohesive energies to the chemical potential of lithium atoms, which is quantified, for instance for a two-phase electrode. The analysis is extended to a single-phase Li x CoO 2 cathode, whose average voltage can be calculated from the cohesive-energy difference between LiCoO 2 and CoO 2 .

Patiromer (Veltassa®) is a crosslinked, insoluble co-polymer drug used as a nonabsorbent potassium binder, approved for treatment of hyperkalemia. Quantitative solid-state 13 C nuclear magnetic resonance (NMR) analysis with comprehensive peak assignment, component quantification, and calculation of mole and weight fractions of monomer units was performed on three doses of patiromer. The workflow is documented in detail. Spectrally edited solid-state 13 C NMR spectra of patiromer show =CH n peaks of matching intensity at 116 and 141 ppm, characteristic of -CH=CH 2 vinyl groups. Similar spectral features can be observed in earlier studies but were previously ignored. In this study, the vinyl signals are well-resolved in a 2-s direct polarization (DP) spectrum without and with dipolar dephasing, which confirms that these sp 2 -hybridized carbons are bonded to hydrogen and partially mobile, consistent with vinyl side groups from incompletely reacted divinyl crosslinkers. The vinyl groups account for 1.6% of all carbon, 3% of the monomer units, and nearly 1/3 of the crosslinkers. Furthermore, an unexpected OCH 3 moiety accounting for ∼1.2% of all carbons was identified by spectral editing; its chemical shift of 54 ppm is more consistent with a methyl ester than with a methyl ether. It can originate from incomplete hydrolysis of ∼6% of methyl-2-fluoroacrylate, the main monomer of patiromer. Characteristic cross peaks in two-dimensional 1 H- 13 C heteronuclear correlation NMR confirm the presence of the vinyl and OCH 3 groups. Trace amounts of xanthan gum are also detected. The quantitative 13 C NMR spectrum of patiromer has been matched in a simulation using a model with five monomer units., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Conventional topochemical photopolymerization reactions occur exclusively in precisely-engineered photoactive crystalline states, which often produces high-insoluble polymers. To mitigate this, here, we report the mechanoactivation of photostable styryldipyrylium-based monomers, which results in their amorphization-enabled solid-state photopolymerization and produces soluble and processable amorphous polymers. A combination of solid-state nuclear magnetic resonance, X-ray diffraction, and absorption/fluorescence spectroscopy reveals the crucial role of a mechanically-disordered monomer phase in yielding polymers via photo-induced [2 + 2] cycloaddition reaction. Hence, mechanoactivation and amorphization can expand the scope of topochemical polymerization conditions to open up opportunities for generating polymers that are otherwise difficult to synthesize and analyze., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Boron trifluoride (BF 3 ) is a highly corrosive gas widely used in industry. Confining BF 3 in porous materials ensures safe and convenient handling and prevents its degradation. Hence, it is highly desired to develop porous materials with high adsorption capacity, high stability, and resistance to BF 3 corrosion. Herein, we designed and synthesized a Lewis basic single-crystalline hydrogen-bond crosslinked organic framework (H C OF-50) for BF 3 storage and its application in catalysis. Specifically, we introduced self-complementary ortho-alkoxy-benzamide hydrogen-bonding moieties to direct the formation of highly organized hydrogen-bonded networks, which were subsequently photo-crosslinked to generate H C OFs. The H C OF-50 features Lewis basic thioether linkages and electron-rich pore surfaces for BF 3 uptake. As a result, H C OF-50 shows a record-high 14.2 mmol/g BF 3 uptake capacity. The BF 3 uptake in H C OF-50 is reversible, leading to the slow release of BF 3 . We leveraged this property to reduce the undesirable chain transfer and termination in the cationic polymerization of vinyl ethers. Polymers with higher molecular weights and lower polydispersity were generated compared to those synthesized using BF 3  ⋅ Et 2 O. The elucidation of the structure-property relationship, as provided by the single-crystal X-ray structures, combined with the high BF 3 uptake capacity and controlled sorption, highlights the molecular understanding of framework-guest interactions in addressing contemporary challenges., (© 2023 Wiley-VCH GmbH.)

Hydroxypropyl methylcellulose acetyl succinate (HPMCAS) is widely used as a pharmaceutical excipient, making a detailed understanding of its tunable structure important for formulation design. Several recently reported peak assignments in the solid-state 13 C NMR spectrum of HPMCAS have been corrected here using peak integrals in quantitative spectra, spectral editing, empirical chemical-shift predictions based on solution NMR, and full spectrum simulation analogous to deconvolution. Unlike in cellulose, the strong peak at 84 ppm must be assigned to C2 and C3 methyl ethers, instead of regular C4 of cellulose. The proposed assignment of signals at <65 ppm to OCH sites, including C5 of cellulose, could not be confirmed. CH 2 spectral editing showed two resolved OCH 2 bands, a more intense one from O-CH 2 ethers of C6 at >69 ppm and a smaller one from its esters and possibly residual CH 2 -OH groups, near 63 ppm. The strong intensities of resolved signals of acetyl, succinoyl, and oxypropyl substituents indicated the substitution of >85% of the OH groups in HPMCAS. The side-group concentrations in three different grades of HPMCAS were quantified., (© 2023 John Wiley & Sons Ltd.)

We address a critical challenge of recovering and recycling homogeneous organocatalysts by designing photoswitchable catalyst structures that display a reversible solubility change in response to light. Initially insoluble catalysts are UV-switched to a soluble isomeric state, which catalyzes the reaction, then back-isomerizes to the insoluble state upon completion of the reaction to be filtered and recycled. The molecular design principles that allow for the drastic solubility change over 10 times between the isomeric states, 87 % recovery by the light-induced precipitation, and multiple rounds of catalyst recycling are revealed. This proof of concept will open up opportunities to develop highly recyclable homogeneous catalysts that are important for the synthesis of critical compounds in various industries, which is anticipated to significantly reduce environmental impact and costs., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Citrate is a critical metabolic substrate and key regulator of energy metabolism in mammalian cells. It has been known for decades that the skeleton contains most (>85%) of the body's citrate, but the question of why and how this metabolite should be partitioned in bone has received singularly little attention. Here, we show that osteoblasts use a specialized metabolic pathway to regulate uptake, endogenous production, and the deposition of citrate into bone. Osteoblasts express high levels of the membranous Na + -dependent citrate transporter solute carrier family 13 member 5 ( Slc13a5 ) gene. Inhibition or genetic disruption of Slc13a5 reduced osteogenic citrate uptake and disrupted mineral nodule formation. Bones from mice lacking Slc13a5 globally, or selectively in osteoblasts, showed equivalent reductions in cortical thickness, with similarly compromised mechanical strength. Surprisingly, citrate content in mineral from Slc13a5 -/- osteoblasts was increased fourfold relative to controls, suggesting the engagement of compensatory mechanisms to augment endogenous citrate production. Indeed, through the coordinated functioning of the apical membrane citrate transporter SLC13A5 and a mitochondrial zinc transporter protein (ZIP1; encoded by Slc39a1 ), a mediator of citrate efflux from the tricarboxylic acid cycle, SLC13A5 mediates citrate entry from blood and its activity exerts homeostatic control of cytoplasmic citrate. Intriguingly, Slc13a5 -deficient mice also exhibited defective tooth enamel and dentin formation, a clinical feature, which we show is recapitulated in primary teeth from children with SLC13A5 mutations. Together, our results reveal the components of an osteoblast metabolic pathway, which affects bone strength by regulating citrate deposition into mineral hydroxyapatite.

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match-based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding selectivity relative to larger apolar compounds. The interactions between the functional group(s) of polar aromatics and the epoxy/hydroxyl groups around the isolated aromatic region of GO enhanced binding selectivity relative to similar-sized apolar aromatics. These findings provide opportunities for precision separations and molecular recognition enabled by size/polarity match-based selectivity.

The energetics of photosynthesis in plants have been re-analyzed in a framework that represents the relatively high energy of O 2 correctly. Starting with the photon energy exciting P680 and "loosening an electron", the energy transfer and electron transport are represented in a comprehensive, self-explanatory sequence of redox energy transfer and release diagrams. The resulting expanded Z-scheme explicitly shows charge separation as well as important high-energy species such as O 2 , Tyr Z ˙, and P680 + ˙, whose energies are not apparent in the classical Z-scheme of photosynthesis. Crucially, the energetics of the three important forms of P680 and of P700 are clarified. The relative free energies of oxidized and reduced species are shown explicitly in kJ/mol, not encrypted in volts. Of the chemical energy produced in photosynthesis, more is stored in O 2 than in glucose. The expanded Z-scheme introduced here provides explanatory power lacking in the classical scheme. It shows that P680* is energetically boosted to P680 + ˙ by the favorable electron affinity of pheophytin and that Photosystem I (PSI) has insufficient energy to split H 2 O and produce O 2 because P700* is too easily ionized. It also avoids the Z-scheme's bewildering implication, according to the "electron waterfall" concept, that H 2 O gives off electrons that spontaneously flow to chlorophyll while releasing energy. The new analysis explains convincingly why plants need two different photosystems in tandem: (i) PSII mostly extracts hydrogen from H 2 O, producing PQH 2 (plastoquinol), and generates the energetically expensive product O 2 ; this step provides little energy directly to the plant; (ii) PSI produces chemical energy for the organism, by pumping protons against a concentration gradient and producing less reluctant hydrogen donors. It also documents that electron transport and energy transfer occur in opposite directions and do not involve redox voltages. The analysis makes it clear that the high-energy species in photosynthesis are unstable, electron-deficient species such as P680 + ˙ and Tyr Z ˙, not putative high-energy electrons.

This study examined conditions that mimic oxidative processes of biomass chars during formation and weathering in the environment. A maple char prepared at the single heat treatment temperature of 500 °C for 2 h was exposed to different thermal oxidation conditions or accelerated oxidative aging conditions prior to sorption of naphthalene or the dication paraquat. Strong chemical oxidation (SCO) was included for comparison. Thermal oxidation caused micropore reaming, with ambient oxidation and SCO much less so. All oxidative treatments incorporated O, acidity, and cation exchange capacity (CEC). Thermal incorporation of O was a function of headspace O 2 concentration and reached a maximum at 350 °C due to the opposing process of burn-off. The CEC was linearly correlated with O/C, but the positive intercept together with nuclear magnetic resonance data signifies that, compared to O groups derived by anoxic pyrolysis, O acquired through oxidation by thermal or ambient routes contributes more to the CEC. Thermal oxidation increased the naphthalene sorption coefficient, the characteristic energy of sorption, and the uptake rate due to pore reaming. By contrast, ambient oxidation (and SCO) suppressed naphthalene sorption by creating a more hydrophilic surface. Paraquat sorption capacity was predicted by an equation that includes a CEC 2 term due to bidentate interaction with pairs of charges, predominating over monodentate interaction, plus a term for the capacity of naphthalene as a reference representing nonspecific driving forces.

The molecular structure of nanothreads produced by the slow compression of 13 C 4 -furan was studied by advanced solid-state NMR. Spectral editing showed that >95% of carbon atoms were bonded to one hydrogen (C-H) and that there were 2-4% CH 2 , 0.6% C═O, and <0.3% CH 3 groups. Alkenes accounted for 18% of the CH moieties, while trapped, unreacted furan made up 7%. Two-dimensional (2D) 13 C- 13 C and 1 H- 13 C NMR identified 12% of all carbon in asymmetric O-CH═CH-CH-CH- and 24% in symmetric O-CH-CH═CH-CH- rings. While the former represented defects or chain ends, some of the latter appeared to form repeating thread segments. Around 10% of carbon atoms were found in highly ordered, fully saturated nanothread segments. Unusually slow 13 C spin-exchange with sites outside the perfect thread segments documented a length of at least 14 bonds; the small width of the perfect-thread signals also implied a fairly long, regular structure. Carbons in the perfect threads underwent relatively slow spin-lattice relaxation, indicating slow spin exchange with other threads and smaller amplitude motions. Through partial inversion recovery, the signals of the perfect threads were observed and analyzed selectively. Previously considered syn -threads with four different C-H bond orientations were ruled out by centerband-only detection of exchange NMR, which was, on the contrary, consistent with anti -threads. The observed 13 C chemical shifts were matched well by quantum-chemical calculations for anti -threads but not for more complex structures like syn / anti -threads. These observations represent the first direct determination of the atomic-level structure of fully saturated nanothreads.

Relationships between dissolved organic matter (DOM) reactivity and chemical composition in a groundwater plume containing petroleum-derived DOM (DOM HC ) were examined by quantitative and qualitative measurements to determine the source and chemical composition of the compounds that persist downgradient. Samples were collected from a transect down the core of the plume in the direction of groundwater flow. An exponential decrease in dissolved organic carbon concentration resulting from biodegradation along the transect correlated with a continuous shift in fluorescent DOM HC from shorter to longer wavelengths. Moreover, ultrahigh resolution mass spectrometry showed a shift from low molecular weight (MW) aliphatic, reduced compounds to high MW, unsaturated (alicyclic/aromatic), high oxygen compounds that are consistent with carboxyl-rich alicyclic molecules. The degree of condensed aromaticity increased downgradient, indicating that compounds with larger, conjugated aromatic core structures were less susceptible to biodegradation. Nuclear magnetic resonance spectroscopy showed a decrease in alkyl (particularly methyl) and an increase in aromatic/olefinic structural motifs. Collectively, data obtained from the combination of these complementary analytical techniques indicated that changes in the DOM HC composition of a groundwater plume are gradual, as relatively low molecular weight (MW), reduced, aliphatic compounds from the oil source were selectively degraded and high MW, alicyclic/aromatic, oxidized compounds persisted., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The composition of fluorescent polymer nanoparticles, commonly referred to as carbon dots, synthesized by microwave-assisted reaction of citric acid and ethylenediamine was investigated by 13 C, 13 C{ 1 H}, 1 H─ 13 C, 13 C{ 14 N}, and 15 N solid-state nuclear magnetic resonance (NMR) experiments. 13 C NMR with spectral editing provided no evidence for significant condensed aromatic or diamondoid carbon phases. 15 N NMR showed that the nanoparticle matrix has been polymerized by amide and some imide formation. Five small, resolved 13 C NMR peaks, including an unusual ═CH signal at 84 ppm ( 1 H chemical shift of 5.8 ppm) and ═CN 2 at 155 ppm, and two distinctive 15 N NMR resonances near 80 and 160 ppm proved the presence of 5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid (IPCA) or its derivatives. This molecular fluorophore with conjugated double bonds, formed by a double cyclization reaction of citric acid and ethylenediamine as first shown by Y. Song, B. Yang, and coworkers in 2015, accounts for the fluorescence of the carbon dots. Cross-peaks in a 1 H─ 13 C HETCOR spectrum with brief 1 H spin diffusion proved that IPCA is finely dispersed in the polyamide matrix. From quantitative 13 C and 15 N NMR spectra, a high concentration (18 ± 2 wt%) of IPCA in the carbon dots was determined. A pronounced gradient in 13 C chemical-shift perturbations and peak widths, with the broadest lines near the COO group of IPCA, indicated at least partial transformation of the carboxylic acid of IPCA by amide or ester formation., (© 2019 John Wiley & Sons, Ltd.)

A comprehensive 13 C nuclear magnetic resonance (NMR) approach for characterizing the location of chain ends of polyethers and polyesters, at the crystallite surface or in the amorphous layers, is presented. The OH chain ends of polyoxymethylene are labeled with 13 COO-acetyl groups and their dynamics probed by 13 C NMR with chemical shift anisotropy (CSA) recoupling. At least three-quarters of the chain ends are not mobile dangling cilia but are immobilized, exhibiting a powder pattern characteristic of the crystalline environment and fast CSA dephasing. The location and clustering of the immobilized chain ends are analyzed by spin diffusion. Fast 1 H spin diffusion from the amorphous regions shows confinement of chain ends to the crystallite surface, corroborated by fast 13 C spin exchange between chain ends. These observations confirm the principle of avoidance of density anomalies, which requires that chains terminate at the crystallite surface to stay out of the crowded interfacial layer., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Molecular miscibility and homogeneity of amorphous solid dispersions (ASDs) are critical attributes that impact physicochemical stability, bioavailability, and processability. Observation of a single glass transition is utilized as a criterion for good mixing of drug substance and polymeric components but can be misleading and cannot quantitatively analyze the domain size at high resolution. While imaging techniques, on the other hand, can characterize phase separation on the particle surface at the nanometer scale, they often require customized sample preparation and handling. Moreover, a mixed system is not necessarily homogeneous. Compared to the numerous studies that have evaluated the mixing of drug substance and polymer in ASDs, inhomogeneity in the phase compositions has remained significantly underexplored. To overcome the analytical challenge, we have developed a 1 H spin diffusion NMR technique to quantify molecular mixing of bulk ASDs at sub-100 nm resolution. It combines relaxation filtering ( T 2H and T 1ρ ) that leaves the active pharmaceutical ingredient (API) as the main source of 1 H magnetization at the start of spin diffusion to the polymer matrix. A spray-dried nifedipine-poly(vinylpyrrolidone) (Nif-PVP) ASD at a 5 wt % drug loading was a homogeneous reference system that exhibited equilibration of magnetization transfer from API to polymer within a short spin diffusion time of ∼3 ms. While fast initial magnetization transfer proving mixing on the 1 nm scale was also observed in Nif-PVP ASDs prepared by hot-melt extrusion (HME) at 186 °C at a 40 wt % drug loading, incomplete equilibration of peak intensities documented inhomogeneity on the ≥30 nm scale. The nonuniformity was confirmed by the partial inversion of the Nif magnetization in the filter that resulted in an even more pronounced deviation from equilibration and by 1 H- 13 C heteronuclear correlation (HETCOR) NMR. It is consistent with the observed differential 1 H spin-lattice relaxation of Nif and PVP as well as a domain structure on the 20 nm scale observed in atomic force microscopy (AFM) images. The incomplete equilibration and differential relaxation were consistently reproduced in a model of two mixed phases of different compositions, e.g., 40 wt % of the ASD with a 15 wt % drug loading and the remaining 60 wt % with a 56 wt % drug loading. Hot-melt extrusion produced more inhomogeneous samples than spray drying for the samples examined in our study. To the best of our knowledge, this spin diffusion NMR method provides currently the highest-resolution quantification of inhomogeneous molecular mixing and phase composition in bulk samples of pharmaceutical dispersions produced with equipment, procedures, and drug loadings that are relevant to industrial drug development.

The molecular connectivity of polymer-metal-organic framework (polyMOF) hybrid materials was investigated using density functional theory calculations and solid-state NMR spectroscopy. The architectural constraints that dictate the formation of polyMOFs were assessed by examining poly(1,4-benzenedicarboxylic acid) (pbdc) polymers in two archetypical MOF lattices (UiO-66 and IRMOF-1). Modeling of the polyMOFs showed that in the IRMOF-1-type lattice, six, seven, and eight methylene (-CH 2 -) groups between 1,4-benzenedicarboxylate (terephthalate, bdc 2- ) units can be accommodated without significant distortions, while in the UiO-66-type lattice, an optimal spacing of seven methylene groups between bdc 2- units is needed to minimize strain. Solid-state NMR supports these predictions and reveals pronounced spectral differences for the same polymer in the two polyMOF lattices. With seven methylene groups, polyUiO-66-7a shows 7 ± 3% of uncoordinated terephthalate linkers, while these are undetectable (<4%) in the corresponding polyIRMOF-1-7a. In addition, NMR-detected backbone mobility is significantly higher in the polyIRMOF-1-7a than in the corresponding polyUiO-66-7a, again indicative of taut chains in the latter.

Efficient cellulose depolymerization is a major bottleneck for economical production of second-generation biofuels. In this work, crystalline cellulose was subjected to sequential ball milling and ethanolysis as a mild and selective depolymerization approach. Ball milling and ethanolysis resulted in 38±1 % cellulose conversion, with 24 % ethyl-glucopyranoside as the main identified and quantified product and negligible side reaction of the ethanol solvent to form diethyl ether. In comparison, ethanolysis of the original cellulose resulted in only 3±1 % conversion. Additional soluble products from cellulose ethanolysis included carbohydrate isomers and oligomers, differing from the products obtained from hydrolysis. X-ray diffraction and nuclear magnetic resonance spectroscopy revealed increased crystallinity post-reaction, retarding further depolymerization. Hot liquid water extracted soluble oligomers from the ethanolyzed cellulose, suggesting formation of a nanoscale barrier of crystalline cellulose that traps soluble products during ethanolysis. Use of cellulose-swelling co-solvents and repeated mechanical decrystallization both proved effective at increasing cellulose conversion and soluble product yields. Repeated ball milling and ethanolysis resulted in 62±1 % cellulose conversion. Ethanolysis of decrystallized cellulose has potential for rapid (<2 h) de-polymerization at mild conditions., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The molecular structure of a crosslinked nitrogen-rich resin made from melamine, urea, and aldehydes, and of microcapsules made from the reactive resin with multiple polymeric components in aqueous dispersion, has been analyzed by 13 C, 13 C{ 1 H}, 1 H- 13 C, 1 H, 13 C{ 14 N}, and 15 N solid-state NMR without isotopic enrichment. Quantitative 13 C NMR spectra of the microcapsules and three precursor materials enable determination of the fractions of different components. Spectral editing of non-protonated carbons by recoupled dipolar dephasing, of CH by dipolar DEPT, and of C-N by 13 C{ 14 N} SPIDER resolves peak overlap and helps with peak assignment. It reveals that the N- and O-rich resin "imitates" the spectrum of polysaccharides such as chitin, cellulose, or Ambergum to an astonishing degree. 15 N NMR can distinguish melamine from urea and guanazole, NC=O from COO, and primary from secondary amines. Such a comprehensive and quantitative analysis enables prediction of the elemental composition of the resin, to be compared with combustion analysis for validation. It also provides a reliable reference for iterative simulations of 13 C NMR spectra from structural models. The conversion from quantitative NMR peak areas of structural components to the weight fractions of interest in industrial practice is derived and demonstrated. Upon microcapsule formation, 15 N and 13 C NMR consistently show loss of urea and aldehyde and an increase in primary amines while melamine is retained. NMR also made unexpected findings, such as imbedded crystallites in one of the resins, as well as persistent radicals in the microcapsules. The crystallites produce distinct sharp lines and are distinguished from liquid-like components by their strong dipolar couplings, resulting in fast dipolar dephasing. Fast 1 H spin-lattice relaxation on the 35-ms time scale and characteristically non-exponential 13 C spin-lattice relaxation indicate persistent radicals, confirmed by EPR. Through 1 H spin diffusion, the mixing of components on the 5-nm scale was documented., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fused-ring aromatics, important skeletal components of black carbon (BC), contribute to long-term carbon (C) sequestration in nature. They have previously been thought to be primarily formed by incomplete combustion of organic materials, whereas the nonpyrogenic origins are negligible. Using advanced solid-state 13 C nuclear magnetic resonance (NMR), including recoupled long-range C-H dipolar dephasing, exchange with protonated and nonprotonated spectral editing (EXPANSE), and dipolar-dephased double-quantum/single-quantum (DQ/SQ) spectroscopy, we for the first time identify fused-ring aromatics that formed during the decomposition of wheat ( Triticum sp.) straw in soil under aerobic, but not anaerobic conditions. The observed formation of polyaromatic units as plant litter decomposes provides direct evidence for humification. Moreover, the estimation of the annual flux of such nonpyrogenic BC could be equivalent to 3-12% of pyrogenic BC added to soils from all other sources. Our findings significantly extend the understanding of potential sources of fused-ring aromatic C and BC in soils as well as the global C cycle.

A fundamental re-assessment of the overall energetics of biochemical electron transfer chains and cycles is presented, highlighting the crucial role of the highest-energy molecule involved, O 2 . The chemical energy utilized by most complex multicellular organisms is not predominantly stored in glucose or fat, but rather in O 2 with its relatively weak (i.e., high-energy) double bond. Accordingly, reactions of O 2 with organic molecules are highly exergonic, while other reactions of glucose, fat, NAD(P)H, or ubiquinol (QH 2 ) are not, as demonstrated in anaerobic respiration with its meager energy output. The notion that "reduced molecules" such as alkanes or fatty acids are energy-rich is shown to be incorrect; they only unlock the energy of more O 2 , compared to O-containing molecules of similar mass. Glucose contains a moderate amount of chemical energy per bond (<20% compared to O 2 ), as confirmed by the relatively small energy output in glycolysis and the Krebs cycle converting glucose to CO 2 and NADH. Only in the "terminal" aerobic respiration reaction with O 2 does a large free energy change occur due to the release of oxygen's stored chemical energy. The actual reaction of O 2 in complex IV of the inner mitochondrial membrane does not even involve any organic fuel molecule and yet releases >1 MJ when 6 mol of O 2 reacts. The traditional presentation that relegated O 2 to the role of a low-energy terminal acceptor for depleted electrons has not explained these salient observations and must be abandoned. Its central notion that electrons release energy because they move from a high-energy donor to a low-energy acceptor is demonstrably false. The energies of (at least) two donor and two acceptor species come into play, and the low "terminal" negative reduction potential in aerobic respiration can be attributed to the unusually high energy of O 2 , the crucial reactant. This is confirmed by comparison with the corresponding half-reaction without O 2 , which is endergonic. In addition, the electrons are mostly not accepted by oxygen but by hydrogen. Redox energy transfer and release diagrams are introduced to provide a superior representation of the energetics of the various species in coupled half-reactions. Electron transport by movement of reduced molecules in the electron transfer chain is shown to run counter to the energy flow, which is carried by oxidized species. O 2 , rather than glucose, NAD(P)H, or ATP, is the molecule that provides the most energy to animals and plants and is crucial for sustaining large complex life forms. The analysis also highlights a significant discrepancy in the proposed energetics of reactions of aerobic respiration, which should be re-evaluated., Competing Interests: The author declares no competing financial interest., (Copyright © 2020 American Chemical Society.)

The cement produced by the Eastern oyster, Crassostrea virginica , may provide blueprints for waterproof biocompatible adhesives synthesized under benign conditions. The composition of this organic-inorganic composite, and of an organic extract, was characterized by 13 C and 1 H solid-state NMR and also compared with  C . virginica shell and its organic extract. Quantification of the organic fraction by 13 C and 1 H NMR spectroscopy consistently showed 3 wt % organics in cement, which was higher than the 1.2 wt % in the shell. According to 13 C NMR with spectral editing, the organic fraction of cement consisted of 73% protein, 25% polysaccharide, and 2% lipid. The organic acid-insoluble extract from the cement was mostly made up of protein remarkably rich in alanine and glycine. The unusual amino acid content matched the composition of silk-like proteins in the C. virginica or C . gigas genomes, including spidron-1-like and shelk2 previously found to be upregulated at the mantle edge. The corresponding extract from the shell contained 32% glycine and was also enriched in serine but not alanine, which was consistent with a previous wet-chemistry study. The 13 C and 1 H NMR spin-lattice relaxation in the organic component of cement and the acid-insoluble extract was 4-40 times faster than in the shell and showed pronounced nonexponentiality, indicating a high concentration of persistent radicals in the organic components of cement, in agreement with a prior EPR study. The presence of radicals in the acid-insoluble cement fraction was confirmed by observation of a paramagnetic shift anisotropy. 13 C NMR corroborated prior observations that the calcium carbonate in the shell and pseudonacre was mostly calcite, whereas cement had an enhanced aragonite fraction. Surprisingly, 1 H- 13 C NMR indicated that aragonite in cement was more distant from the organic fraction than was calcite. These results help advance our understanding of how oysters achieve adhesion within their wet environment.

Isomerization behaviors of spiropyran derivatives in neat condensed phase were studied to understand their unusual phase transitions including cold-crystallization after extreme supercooling down to -50 °C. Compounds with different functional groups were compared, and the equilibrium between isomers at high temperatures was found to determine phase transitions.

Solid-state NMR has been used to study mixed-matrix membranes (MMMs) prepared with a metal-organic framework (MOF, UiO-66) and two different high molecular weight polymers (PEO and PVDF). 13 C and 1 H NMR data provide overwhelming evidence that most UiO-66 organic linkers are within 1 nm of PEO, which indicates that PEO is homogeneously distributed throughout the MOF. Systematic changes in MOF 13 C NMR peak positions and 1 H NMR line widths, as well as dramatic reductions in the MOF 1 H T 1ρ relaxation times, are observed as the PEO content increases, and when the pores have been filled, a further increase in PEO results in the formation of semicrystalline PEO outside the UiO-66 particles. In contrast, similar studies on PVDF MMMs show that the polymer contacts only a small fraction (<20%) of the MOF linkers. Simulations confirm that PEO penetrates into UiO-66 more easily than does PVDF. These studies are among the first to provide experimental insights into MOF-polymer interactions in an MMM.

A convenient one-dimensional magic-angle spinning NMR method is presented that provides selective NMR spectra of COH moieties in uniformly 13 C-enriched organic materials. This method, termed hydroxyl-proton selection (HOPS), eliminates the magnetization of protons directly bonded to carbons by recoupling the 1 H- 13 C dipolar interaction for a short time (∼70 μs), which also serves as a chemical-shift filter to suppress 1 H magnetization of CH 3 groups. After cross polarization to 13 C, the signals of COH and COOH carbons are observed selectively. This makes it possible to distinguish alcohols from ethers, in particular phenols from aromatic ethers such as the furans often formed by dehydration of glucose, and carboxylic acids from carboxylates and ethers. HOPS NMR reveals that orthodiphenols are often a major component of low-temperature carbon materials. For instance, it forces the reassignment of the 143 ppm 13 C NMR signal of hydrothermal carbon to such catecholic diphenols, while a previous NMR-based structural model had attributed this peak to a central furan-furan linkage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A Zr metal-organic framework (MOF) 1-CoCl 3 has been synthesized by solvothermal reaction of ZrCl 4 with a carboxylic acid-functionalized Co III -P N N N P pincer complex H 4 (L-CoCl 3 ) ([L-CoCl 3 ] 4- = [(2,6-(NHPAr 2 ) 2 C 6 H 3 )CoCl 3 ] 4- , Ar = p-C 6 H 4 CO 2 - ). The structure of 1-CoCl 3 has been determined by X-ray powder diffraction and exhibits a csq topology that differs from previously reported ftw-net Zr MOFs assembled from related Pd II - and Pt II -P N N N P pincer complexes. The Co-P N N N P pincer species readily demetallate upon reduction of Co III to Co II , allowing for transmetalation with late second and third row transition metals in both the homogeneous complex and 1-CoCl 3 . Reaction of 1-CoCl 3 with [Rh(nbd)Cl] 2 (nbd = 2,5-nobornadiene) results in complete Rh/Co metal exchange at the supported diphosphine pincer complexes to generate 1-RhCl, which has been inaccessible by direct solvothermal synthesis. Treating 1-CoCl 3 with PtCl 2 (SMe 2 ) 2 in the presence of the mild reductant NEt 3 resulted in nearly complete Co substitution by Pt. In addition, a mixed metal pincer MOF, 1-PtRh, was generated by sequential substitution of Co with Pt followed by Rh.

A one-dimensional (1D) sp 3 carbon nanomaterial with high lateral packing order, known as carbon nanothreads, has recently been synthesized by slowly compressing and decompressing crystalline solid benzene at high pressure. The atomic structure of an individual nanothread has not yet been determined experimentally. We have calculated the 13 C nuclear magnetic resonance (NMR) chemical shifts, chemical shielding tensors, and anisotropies of several axially ordered and disordered partially saturated and fully saturated nanothreads within density functional theory and systematically compared the results with experimental solid-state NMR data to assist in identifying the structures of the synthesized nanothreads. In the fully saturated threads, every carbon atom in each progenitor benzene molecule has bonded to a neighboring molecule (i.e., 6 bonds per molecule, a so-called "degree-6" nanothread), while the partially saturated threads examined retain a single double bond per benzene ring ("degree-4"). The most-parsimonious theoretical fit to the experimental 1D solid-state NMR spectrum, constrained by the measured chemical shift anisotropies and key features of two-dimensional NMR spectra, suggests a certain combination of degree-4 and degree-6 nanothreads as plausible components of this 1D sp 3 carbon nanomaterial, with intriguing hints of a [4 + 2] cycloaddition pathway toward nanothread formation from benzene columns in the progenitor molecular crystal, based on the presence of nanothreads IV-7, IV-8, and square polymer in the minimal fit.

Carbon nanothreads are a new type of one-dimensional sp 3 -carbon nanomaterial formed by slow compression and decompression of benzene. We report characterization of the chemical structure of 13 C-enriched nanothreads by advanced quantitative, selective, and two-dimensional solid-state nuclear magnetic resonance (NMR) experiments complemented by infrared (IR) spectroscopy. The width of the NMR spectral peaks suggests that the nanothread reaction products are much more organized than amorphous carbon. In addition, there is no evidence from NMR of a second phase such as amorphous mixed sp 2 /sp 3 -carbon. Spectral editing reveals that almost all carbon atoms are bonded to one hydrogen atom, unlike in amorphous carbon but as is expected for enumerated nanothread structures. Characterization of the local bonding structure confirms the presence of pure fully saturated "degree-6" carbon nanothreads previously deduced on the basis of crystal packing considerations from diffraction and transmission electron microscopy. These fully saturated threads comprise between 20% and 45% of the sample. Furthermore, 13 C- 13 C spin exchange experiments indicate that the length of the fully saturated regions of the threads exceeds 2.5 nm. Two-dimensional 13 C- 13 C NMR spectra showing bonding between chemically nonequivalent sites rule out enumerated single-site thread structures such as polytwistane or tube (3,0) but are consistent with multisite degree-6 nanothreads. Approximately a third of the carbon is in "degree-4" nanothreads with isolated double bonds. The presence of doubly unsaturated degree-2 benzene polymers can be ruled out on the basis of 13 C- 13 C NMR with spin exchange rate constants tuned by rotational resonance and 1 H decoupling. A small fraction of the sample consists of aromatic rings within the threads that link sections with mostly saturated bonding. NMR provides the detailed bonding information necessary to refine solid-state organic synthesis techniques to produce pure degree-6 or degree-4 carbon nanothreads.

Hydrothermally stable carbon overlayers can protect mesoporous oxides (SiO₂ and Al₂O₃) from hydrolysis during aqueous-phase catalysis. Overlayers made at 800 &deg;C by pyrolysis of 2,3-naphthalenediol deposited out of acetone solution were analyzed by solid-state 13 C nuclear magnetic resonance (NMR) spectroscopy. Power absorption due to sample conductivity was prevented by diluting the sample in nonconductive and background-free tricalcium phosphate. While pyrolysis on SiO₂ produced a predominantly aromatic carbon film, at least 15% of nonaromatic carbon (sp³-hybridized C as well as C=O) was observed on &gamma;-Al₂O₃. These species were not derived from residual solvent, according to spectra of the same material treated at 400 &deg;C. The sp³-hybridized C exhibited weak couplings to hydrogen, short spin-lattice relaxation times, and unusually large shift anisotropies, which are characteristics of tetrahedral carbon with high concentrations of unpaired electrons. Moderate heat treatment at 400 &deg;C on SiO₂ and Al₂O₃ resulted in yellow-brown and nearly black samples, respectively, but the darker color on Al₂O₃ did not correspond to more extensive carbonization. Aromatic carbon bonded to hydrogen remained predominant and the peaks of naphthalenediol were still recognizable; however, some of the chemical shifts differed by up to 5 ppm, indicating significant differences in local structure. On SiO₂, additional sharp peaks were detected and attributed to 1/3 of the 2,3-naphthalene molecules undergoing fast, nearly isotropic motions.

Carbon nanothreads are a new one-dimensional sp 3 carbon nanomaterial. They assemble into hexagonal crystals in a room temperature, nontopochemical solid-state reaction induced by slow compression of benzene to 23 GPa. Here we show that pyridine also reacts under compression to form a well-ordered sp 3 product: C 5 NH 5 carbon nitride nanothreads. Solid pyridine has a different crystal structure from solid benzene, so the nontopochemical formation of low-dimensional crystalline solids by slow compression of small aromatics may be a general phenomenon that enables chemical design of properties. The nitrogen in the carbon nitride nanothreads may improve processability, alters photoluminescence, and is predicted to reduce the bandgap.

Carboxylic acid-functionalized Pd and Pt P N N N P pincer complexes were used for the assembly of two porous Zr metal-organic frameworks (MOFs), 2-PdX and 2-PtX. Powder X-ray diffraction analysis shows that the new MOFs adopt cubic framework structures similar to the previously reported Zr 6 O 4 (OH) 4 [(P O C O P)PdX] 3 , [P O C O P = 2,6-(OPAr 2 ) 2 C 6 H 3 ); Ar = p-C 6 H 4 CO 2 - , X = Cl - , I - ] (1-PdX). Elemental analysis and spectroscopic characterization indicate the presence of missing linker defects, and 2-PdX and 2-PtX were formulated as Zr 6 O 4 (OH) 4 (OAc) 2.4 [M(P N N N P)X] 2.4 [M = Pd, Pt; P N N N P = 2,6-(HNPAr 2 ) 2 C 5 H 3 N; Ar = p-C 6 H 4 CO 2 - ; X = Cl - , I - ]. Postsynthetic halide ligand exchange reactions were carried out by treating 2-PdX with Ag(O 3 SCF 3 ) or NaI followed by PhI(O 2 CCF 3 ) 2 . The latter strategy proved to be more effective at activating the MOF for the catalytic intramolecular hydroamination of an o-substituted alkynyl aniline, underscoring the advantage of using halide exchange reagents that produce soluble byproducts.

New information on the chemical composition of dissolved organic matter (DOM) in three lakes in Minnesota has been gained from spectral editing and two-dimensional nuclear magnetic resonance (NMR) methods, indicating the effects of lake hydrological settings on DOM composition. Williams Lake (WL), Shingobee Lake (SL), and Manganika Lake (ML) had different source inputs, and the lake water residence time (WRT) of WL was markedly longer than that of SL and ML. The hydrophobic organic acid (HPOA) and transphilic organic acid (TPIA) fractions combined comprised >50% of total DOM in these lakes, and contained carboxyl-rich alicyclic molecules (CRAM), aromatics, carbohydrates, and N-containing compounds. The previously understudied TPIA fractions contained fewer aromatics, more oxygen-rich CRAM, and more N-containing compounds compared to the corresponding HPOA. CRAM represented the predominant component in DOM from all lakes studied, and more so in WL than in SL and ML. Aromatics including lignin residues and phenols decreased in relative abundances from ML to SL and WL. Carbohydrates and N-containing compounds were minor components in both HPOA and TPIA and did not show large variations among the three lakes. The increased relative abundances of CRAM in DOM from ML, SL to WL suggested the selective preservation of CRAM with increased residence time.

Improved multiple cross polarization (multiCP) pulse sequences for quickly acquiring quantitative 13 C NMR spectra of organic solids are presented. Loss of 13 C magnetization due to imperfect read-out and storage pulses in multiCP has been identified as a significant mechanism limiting polarization enhancement for 13 C sites with weak couplings to 1 H. This problem can be greatly reduced by composite 90° pulses with non-orthogonal phases that flip the magnetization onto the spin-lock field and back to the longitudinal direction for the 1 H repolarization period; the observed loss is <3% for over ±10 kHz resonance offset and up to 20% flip-angle error. This composite-pulse multiCP (ComPmultiCP) sequence consistently provides performance superior to that of conventional multiCP, without any trade-off. The longer total CP time enabled by the composite pulses allows for a wider amplitude ramp during CP, which decreases the sensitivity to Hartmann-Hahn mismatch by a factor of two, with a <7% root-mean-square deviation within a 1-dB range for Boc-alanine. In samples with very short T 1ρ , under-polarization of non-protonated carbons can be compensated by slight dipolar dephasing of CH n signals resulting from relatively weak decoupling during the Hahn spin echo period before detection. Quantitative spectra have been obtained by ComPmultiCP for low-crystallinity branched polyethylene at 4.5 kHz MAS, and in combination with partial dipolar dephasing for soil organic matter at 14 kHz MAS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dissolved organic nitrogen (DON) comprises the largest pool of fixed N in the surface ocean, yet its composition has remained poorly constrained. Knowledge of the chemical composition of this nitrogen pool is crucial for understanding its biogeochemical function and reactivity in the environment. Previous work has suggested that high-molecular-weight (high-MW) DON exists only in two closely related forms, the secondary amides of peptides and of N-acetylated hexose sugars. Here, we demonstrate that the chemical structures of high-MW DON may be much more diverse than previously thought. We couple isotopic labeling of cyanobacterially derived dissolved organic matter with advanced two-dimensional NMR spectroscopy to open the "black box" of uncharacterized high-MW DON. Using multibond NMR correlations, we have identified novel N-methyl-containing amines and amides, primary amides, and novel N-acetylated sugars, which together account for nearly 50% of cyanobacterially derived high-MW DON. This study reveals unprecedented compositional details of the previously uncharacterized DON pool and outlines the means to further advance our understanding of this biogeochemically and globally important reservoir of organic nitrogen.

Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially a systematic approach to NOM characterization, and their applications to the study of NOM. We discuss some basics of how to acquire high-quality and quantitative solid-state 13 C NMR spectra, and address some common technical mistakes that lead to unreliable spectra of NOM. The identification of specific functional groups in NOM, primarily based on 13 C spectral-editing techniques, is described and the theoretical background of some recently-developed spectral-editing techniques is provided. Applications of solid-state NMR to investigating nitrogen (N) in NOM are described, focusing on limitations of the widely used 15 N CP/MAS experiment and the potential of improved advanced NMR techniques for characterizing N forms in NOM. Then techniques used for identifying proximities, heterogeneities and domains are reviewed, and some examples provided. In addition, NMR techniques for studying segmental dynamics in NOM are reviewed. We also briefly discuss applications of solid-state NMR to NOM from various sources, including soil organic matter, aquatic organic matter, organic matter in atmospheric particulate matter, carbonaceous meteoritic organic matter, and fossil fuels. Finally, examples of NMR-based structural models and an outlook are provided., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hydrogels consisting of carboxylic acid groups and N-isopropylacrylamide as pendants on their polymeric network usually exhibit volume expansion upon deprotonation or volume contraction when being heated. Demonstrated here is an anti-intuitive case of a hydrogel containing multiple carboxylic acid groups at each crosslinking point in the polymeric network, which shrinks upon increasing pH from 1 to 7 at 37 °C or expands upon heating from 25 to 37 °C at pH 1. The unexpected volume change originates from the high percentage of the crosslinker in the polymers, as detected by solid-state 13 C NMR spectroscopy. In addition, the volume changes are thermally reversible. As the first example of the use of functional hyper-crosslinkers to control the pH and thermal responses of nanogels, this work illustrates a new way to design soft materials with unusual behaviors., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report that phosphotyrosine-cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This enzymatic conversion also results in the assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Preliminary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and microtubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers.

The manufacture of advanced polyolefins has been critically enabled by the development of single-site heterogeneous catalysts. Metal-organic frameworks (MOFs) show great potential as heterogeneous catalysts that may be designed and tuned on the molecular level. In this work, exchange of zinc ions in Zn5Cl4(BTDD)3, H2BTDD = bis(1H-1,2,3-triazolo[4,5-b],[4',5'-i])dibenzo[1,4]dioxin) (MFU-4l) with reactive metals serves to establish a general platform for selective olefin polymerization in a high surface area solid promising for industrial catalysis. Characterization of polyethylene produced by these materials demonstrates both molecular and morphological control. Notably, reactivity approaches single-site catalysis, as evidenced by low polydispersity indices, and good molecular weight control. We further show that these new catalysts copolymerize ethylene and propylene. Uniform growth of the polymer around the catalyst particles provides a mechanism for controlling the polymer morphology, a relevant metric for continuous flow processes.

A porous metal-organic framework Zr6O4(OH)4(L-PdX)3 (1-X) has been constructed from Pd diphosphinite pincer complexes ([L-PdX](4-) = [(2,6-(OPAr2)2C6H3)PdX](4-), Ar = p-C6H4CO2(-), X = Cl, I). Reaction of 1-X with PhI(O2CCF3)2 facilitates I(-)/CF3CO2(-) ligand exchange to generate 1-TFA and I2 as a soluble byproduct. 1-TFA is an active and recyclable catalyst for transfer hydrogenation of benzaldehydes using formic acid as a hydrogen source. In contrast, the homogeneous analogue (t)Bu(L-PdTFA) is an ineffective catalyst owing to decomposition under the catalytic conditions, highlighting the beneficial effects of immobilization.

We have determined refined multidimensional chemical shift ranges for intra-residue correlations ((13)C-(13)C, (15)N-(13)C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 (13)C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited "hand-picked" data sets, we show that ~94% of the (13)C NMR data and almost all (15)N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6% of the (13)C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. -2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra-residue cross peaks by inspection or by using a provided command-line Python script (PLUQin), which should be useful in protein structure determination. The refined chemical shift distributions are utilized in a simple quality test (SQAT) that should be applied to new protein NMR data before deposition in a databank, and they could benefit many other chemical-shift based tools.

The four aromatic amino acids in proteins, namely histidine, phenylalanine, tyrosine, and tryptophan, have strongly overlapping (13)C chemical shift ranges between 100 and 160ppm, and have so far been largely neglected in solid-state NMR determination of protein structures. Yet aromatic residues play important roles in biology through π-π and cation-π interactions. To better resolve and assign aromatic residues' (13)C signals in magic-angle-spinning (MAS) solid-state NMR spectra, we introduce two spectral editing techniques. The first method uses gated (1)H decoupling in a proton-driven spin-diffusion (PDSD) experiment to remove all protonated (13)C signals and retain only non-protonated carbon signals in the aromatic region of the (13)C spectra. The second technique uses chemical shift filters and (1)H-(13)C dipolar dephasing to selectively detect the Cα, Cβ and CO cross peaks of aromatic residues while suppressing the signals of all aliphatic residues. We demonstrate these two techniques on amino acids, a model peptide, and the microcrystalline protein GB1, and show that they significantly simplify the 2D NMR spectra and both reveal and permit the ready assignment of the aromatic residues' signals., (Copyright © 2015 Elsevier Inc. All rights reserved.)