A gut-derived metabolite alters brain activity and anxiety behaviour in mice.

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

Acid Catalysis over Low-Silica Faujasite Zeolites.

Low-silica faujasite (FAU) zeolites (with Si/Al ratio of ca. 1.2-1.8) sustain framework integrity and porosity upon moderate ion exchange (0.01 M NH4NO3 solution for 1 h at ambient temperature), which introduces two kinds of protons, distinctive in reactivity and coordination to the zeolite framework, within supercages (HSUP). Moderate ion exchange limited within supercages transpires while maintaining full occupancy of Na+ cations within associated sodalite cages; this in turn helps stabilize the framework of low-silica H-FAU zeolites. Protons located on site II (H3630) and site III (H3650) within supercages on low-silica FAU zeolites can be classified and enumerated by virtue of infrared spectroscopy, providing an opportunity to compare reactivities of these distinct protons for monomolecular protolytic reactions of propane. Protons on site II exhibit prominently higher reactivity for monomolecular propane dehydrogenation and cracking than protons on site III. Low-silica proton-form FAU zeolites (zeolite X) upon moderate ion exchange possess protons on site III that are unavailable on high-silica FAU zeolites (zeolite Y) and limit ion exchange within supercages, providing unprecedented high-temperature structural and chemical stability (>773 K) and enabling their application as solid-acid catalysts.

Enhanced Reactivity of Accessible Protons in Sodalite Cages of Faujasite Zeolite.

Faujasite (FAU) zeolites (with Si/Al ratio of ca. 1.7) undergo mild dealumination at moderate ion exchange conditions (0.01 to 0.6 M of NH4 NO3 solutions) resulting in protons circumscribed by sodalite cages becoming accessible for reaction without conspicuous changes to bulk crystallinity. The ratio of protons in sodalite cages (HSOD ) to supercages (HSUP ) can be systematically manipulated from 0 to ca. 1 by adjusting ammonium concentrations used in ion exchange. The fraction of accessible protons in the sodalite cages is assessed by virtue of infrared spectra for H-D exchange of deuterated propane based on the band area ratio of OD2620 /OD2680 (ODSOD /ODSUP ). Protons in sodalite cages (HSOD ) show higher rate constants of propane dehydrogenation (kD ) and cracking (kC ) than protons in supercages (HSUP ) plausibly due to confinement effects being more prominent in smaller voids. Rate constants of dehydrogenation and cracking including kD /kC ratios are also augmented as the fraction of accessible protons in the sodalite cages is enhanced. These effects of accessibility and reactivity of protons in sodalite cages hitherto inconspicuous are revealed herein via methods that systematically increase accessibility of cations located in sodalite cages.

SSZ-27: A Small-Pore Zeolite with Large Heart-Shaped Cavities Determined by Using Multi-crystal Electron Diffraction.

The high-silica zeolite SSZ-27 was synthesized using one of the isomers of the organic structure-directing agent that is known to produce the large-pore zeolite SSZ-26 (CON). The structure of the as-synthesized form was solved using multi-crystal electron diffraction data. Data were collected on eighteen crystals, and to obtain a high-quality and complete data set for structure refinement, hierarchical cluster analysis was employed to select the data sets most suitable for merging. The framework structure of SSZ-27 can be described as a combination of two types of cavities, one of which is shaped like a heart. The cavities are connected through shared 8-ring windows to create straight channels that are linked together in pairs to form a one-dimensional channel system. Once the framework structure was known, molecular modelling was used to find the best fitting isomer, and this, in turn, was isolated to improve the synthesis conditions for SSZ-27.

Ultraparamagnetic Cells Formed through Intracellular Oxidation and Chelation of Paramagnetic Iron.

Making cells magnetic is a long-standing goal of chemical biology, aiming to enable the separation of cells from complex biological samples and their visualization in vivo using magnetic resonance imaging (MRI). Previous efforts towards this goal, focused on engineering cells to biomineralize superparamagnetic or ferromagnetic iron oxides, have been largely unsuccessful due to the stringent required chemical conditions. Here, we introduce an alternative approach to making cells magnetic, focused on biochemically maximizing cellular paramagnetism. We show that a novel genetic construct combining the functions of ferroxidation and iron chelation enables engineered bacterial cells to accumulate iron in "ultraparamagnetic" macromolecular complexes, allowing these cells to be trapped with magnetic fields and imaged with MRI in vitro and in vivo. We characterize the properties of these cells and complexes using magnetometry, nuclear magnetic resonance, biochemical assays, and computational modeling to elucidate the unique mechanisms and capabilities of this paramagnetic concept.

Understanding CO2 capture mechanisms in aqueous hydrazine via combined NMR and first-principles studies.

Aqueous amines are currently the most promising solution for large-scale CO2 capture from industrial sources. However, molecular design and optimization of amine-based solvents have proceeded slowly due to a lack of understanding of the underlying reaction mechanisms. Unique and unexpected reaction mechanisms involved in CO2 absorption into aqueous hydrazine are identified using 1H, 13C, and 15N NMR spectroscopy combined with first-principles quantum-mechanical simulations. We find production of both hydrazine mono-carbamate (NH2-NH-COO-) and hydrazine di-carbamate (-OOC-NH-NH-COO-), with the latter becoming more populated with increasing CO2 loading. Exchange NMR spectroscopy also demonstrates that the reaction products are in dynamic equilibrium under ambient conditions due to CO2 exchange between mono-carbamate and di-carbamate as well as fast proton transfer between un-protonated free hydrazine and mono-carbamate. The exchange rate rises steeply at high CO2 loadings, enhancing CO2 release, which appears to be a unique property of hydrazine in aqueous solution. The underlying mechanisms of these processes are further evaluated using quantum mechanical calculations. We also analyze and discuss reversible precipitation of carbamate and conversion of bicarbonate to carbamates. The comprehensive mechanistic study provides useful guidance for optimal design of amine-based solvents and processes to reduce the cost of carbon capture. Moreover, this work demonstrates the value of a combined experimental and computational approach for exploring the complex reaction dynamics of CO2 in aqueous amines.

Guest-host interactions of a rigid organic molecule in porous silica frameworks.

Molecular-level interactions at organic-inorganic interfaces play crucial roles in many fields including catalysis, drug delivery, and geological mineral precipitation in the presence of organic matter. To seek insights into organic-inorganic interactions in porous framework materials, we investigated the phase evolution and energetics of confinement of a rigid organic guest, N,N,N-trimethyl-1-adamantammonium iodide (TMAAI), in inorganic porous silica frameworks (SSZ-24, MCM-41, and SBA-15) as a function of pore size (0.8 nm to 20.0 nm). We used hydrofluoric acid solution calorimetry to obtain the enthalpies of interaction between silica framework materials and TMAAI, and the values range from -56 to -177 kJ per mole of TMAAI. The phase evolution as a function of pore size was investigated by X-ray diffraction, IR, thermogravimetric differential scanning calorimetry, and solid-state NMR. The results suggest the existence of three types of inclusion depending on the pore size of the framework: single-molecule confinement in a small pore, multiple-molecule confinement/adsorption of an amorphous and possibly mobile assemblage of molecules near the pore walls, and nanocrystal confinement in the pore interior. These changes in structure probably represent equilibrium and minimize the free energy of the system for each pore size, as indicated by trends in the enthalpy of interaction and differential scanning calorimetry profiles, as well as the reversible changes in structure and mobility seen by variable temperature NMR.

Catalytic consequences of open and closed grafted Al(III)-calix[4]arene complexes for hydride and oxo transfer reactions.

An approach for the control and understanding of supported molecular catalysts is demonstrated with the design and synthesis of open and closed variants of a grafted Lewis acid active site, consisting of Al(III)-calix[4]arene complexes on the surface of silica. The calixarene acts as a molecular template that enforces open and closed resting-state coordination geometries surrounding the metal active sites, due to its lower-rim substituents as well as site isolation by virtue of its steric bulk. These sites are characterized and used to elucidate mechanistic details and connectivity requirements for reactions involving hydride and oxo transfer. The consequence of controlling open versus closed configurations of the grafted Lewis acid site is demonstrated by the complete lack of observed activity of the closed site for Meerwein-Ponndorf-Verley (MPV) reduction; whereas, the open variant of this catalyst has an MPV reduction activity that is virtually identical to previously reported soluble molecular Al(III)-calix[4]arene catalysts. In contrast, for olefin epoxidation using tert-butyl-hydroperoxide as oxidant, the open and closed catalysts exhibit similar activity. This observation suggests that for olefin epoxidation catalysis using Lewis acids as catalyst and organic hydroperoxide as oxidant, covalent binding of the hydroperoxide is not required, and instead dative coordination to the Lewis acid center is sufficient for catalytic oxo transfer. This latter result is supported by density functional theory calculations of the transition state for olefin epoxidation catalysis, using molecular analogs of the open and closed catalysts.

Metalloenzyme-like catalyzed isomerizations of sugars by Lewis acid zeolites.

Isomerization of sugars is used in a variety of industrially relevant processes and in glycolysis. Here, we show that hydrophobic zeolite beta with framework tin or titanium Lewis acid centers isomerizes sugars, e.g., glucose, via reaction pathways that are analogous to those of metalloenzymes. Specifically, experimental and theoretical investigations reveal that glucose partitions into the zeolite in the pyranose form, ring opens to the acyclic form in the presence of the Lewis acid center, isomerizes into the acyclic form of fructose, and finally ring closes to yield the furanose product. The zeolite catalysts provide processing advantages over metalloenzymes such as an ability to work at higher temperatures and in acidic conditions that allow for the isomerization reaction to be coupled with other important conversions.

Studies of aluminum reinsertion into borosilicate zeolites with intersecting channels of 10- and 12-ring channel systems.

The work here describes the kinetic analyses of aluminum replacement for boron in a suite of borosilicate molecular sieves. While the method has been described before as a means of converting synthesized borosilicates (with weak inherent acidity) to aluminosilicates (with much stronger acid strength) when there are large pores in the structure, here we carry out the transformation under less than optimal replacement concentrations, in order to better follow the kinetics. We examined several zeolite structures with boundary conditions of boron MEL where there are only 10-ring (or intermediate) pore structures and no Al is taken up, to multidimensional large pore zeolites, like boron beta, where Al substitution can occur everywhere. We also studied materials with both intermediate and large pores, SSZ-56, 57, 70, and 82. In the case of 57 up to 90% of the structure is made up of boron MEL. We observe that the pH drop is proportional to the Al reinsertion and is the same for all zeolites we studied. In one case, we compared a zeolite (SSZ-24) with boron and then no boron sites and found that Al does not go into defect sites. It was again confirmed (shown in earlier work) that Al will go into nest sites created by boron hydrolysis out of the substrate before Al treatment. Along those lines we also made two new observations: (1) the profile for Al uptake, as followed by pH drop, is the same kinetically, whether the boron is there or not; and (2) NMR showed that the boron is leaving the structure faster than Al can go back in (SSZ-33 study), even when we treat a material with boron in the lattice.

Single-step delamination of a MWW borosilicate layered zeolite precursor under mild conditions without surfactant and sonication.

Layered borosilicate zeolite precursor ERB-1P (Si/B = 11) is delaminated via isomorphous substitution of Al for B using a simple aqueous Al(NO3)3 treatment. Characterization by PXRD shows loss of long-range order, and TEM demonstrates transformation of rectilinear layers in the precursor to single and curved layers in the delaminated material. N2 physisorption and base titration confirm the expected decrease of micropore volume and increase in external surface area for delaminated materials relative to their calcined 3D zeolite counterpart, whereas FTIR and multinuclear NMR spectroscopies demonstrate synthesis of Brønsted acid sites upon delamination. Comparative synthetic studies demonstrate that this new delamination method requires (i) a borosilicate layered zeolite precursor, in which boron atoms can be isomorphously substituted by aluminum, (ii) neutral amine pore fillers instead of rigid and large quaternary amine SDAs, and (iii) careful temperature control, with the preferred temperature window being around 135 °C for ERB-1P delamination. Acylation of 2-methoxynaphthalene was used as a model reaction to investigate the catalytic benefits of delamination. A partially dealuminated delaminated material displays a 2.3-fold enhancement in its initial rate of catalysis relative to the 3D calcined material, which is nearly equal to its 2.5-fold measured increase in external surface area. This simple, surfactant- and sonication-free, mild delamination method is expected to find broad implementation for the synthesis of delaminated zeolite catalysts.

Desolvation and dehydrogenation of solvated magnesium salts of dodecahydrododecaborate: relationship between structure and thermal decomposition.

Attempts to synthesize solvent-free MgB12H12 by heating various solvated forms (H2O, NH3, and CH3OH) of the salt failed because of the competition between desolvation and dehydrogenation. This competition has been studied by thermogravimetric analysis (TGA) and temperature-programmed desorption (TPD). Products were characterized by IR, solution- and solid-state NMR spectroscopy, elemental analysis, and single-crystal or powder X-ray diffraction analysis. For hydrated salts, thermal decomposition proceeded in three stages, loss of water to form first hexahydrated then trihydrated, and finally loss of water and hydrogen to form polyhydroxylated complexes. For partially ammoniated salts, two stages of thermal decomposition were observed as ammonia and hydrogen were released with weight loss first of 14 % and then 5.5 %. Thermal decomposition of methanolated salts proceeded through a single step with a total weight loss of 32 % with the release of methanol, methane, and hydrogen. All the gaseous products of thermal decomposition were characterized by using mass spectrometry. Residual solid materials were characterized by solid-state (11)B magic-angle spinning (MAS) NMR spectroscopy and X-ray powder diffraction analysis by which the molecular structures of hexahydrated and trihydrated complexes were solved. Both hydrogen and dihydrogen bonds were observed in structures of [Mg(H2O)6B12H12]⋅6 H2O and [Mg(CH3OH)6B12H12]⋅6 CH3OH, which were determined by single-crystal X-ray diffraction analysis. The structural factors influencing thermal decomposition behavior are identified and discussed. The dependence of dehydrogenation on the formation of dihydrogen bonds may be an important consideration in the design of solid-state hydrogen storage materials.

Metal-free, polyether-mediated H2-release from ammonia borane: roles of hydrogen bonding interactions in promoting dehydrogenation.

Polyetheral additives were found to be efficient promoters to enhance the rate of H2-release from ammonia borane (AB) at various temperatures. In particular, tetraethylene glycol dimethyl ether (T4EGDE, 29 wt% relative to AB + T4EGDE) exhibited significantly improved activities for AB dehydrogenation, with the material-based hydrogen storage capacity of 10.3 wt% at 125 °C within 40 min. In situ FT-IR spectroscopy indicated the formation of B-(cyclodiborazanyl)amino-borohydride (BCDB), borazine, and µ-aminodiborane as gaseous byproducts. In addition, (11)B nuclear magnetic resonance (NMR) spectroscopy further revealed that diammoniate of diborane (DADB) was initially formed to give polyaminoborane as liquid and/or solid spent-fuel, consistent with previous reports. Density Functional Theory (DFT) calculations suggested that hydrogen bonding interactions between AB and a polyetheral promoter initially played an important role in increasing the reactivity of B-H bonds of AB by transferring electron density from oxygen atoms of the promoter into B-H bonds of AB. These partially activated, hydridic B-H bonds were proposed to help promote the formation of diammoniate of diborane (DADB), which is considered as a reactive intermediate, eventually enhancing the rate of H2-release from AB. In addition, our in situ solid state (11)B magic angle spinning (MAS) NMR measurements further confirmed that the rate of DADB formation from AB with a small quantity of T4EGDE was found to be much faster than that of pristine AB even at 50 °C. This metal-free method for H2-release from AB with an added, small quantity of polyethers would be helpful to develop feasible hydrogen storage systems for long-term fuel cell applications.

Synthesis and characterization of a lithium-doped fullerane (Li(x)-C60-H(y)) for reversible hydrogen storage.

Herein, we present a lithium-doped fullerane (Li(x)-C(60)-H(y)) that is capable of reversibly storing hydrogen through chemisorption at elevated temperatures and pressures. This system is unique in that hydrogen is closely associated with lithium and carbon upon rehydrogenation of the material and that the weight percent of H(2) stored in the material is intimately linked to the stoichiometric ratio of Li:C(60) in the material. Characterization of the material (IR, Raman, UV-vis, XRD, LDI-TOF-MS, and NMR) indicates that a lithium-doped fullerane is formed upon rehydrogenation in which the active hydrogen storage material is similar to a hydrogenated fullerene. Under optimized conditions, a lithium-doped fullerane with a Li:C(60) mole ratio of 6:1 can reversibly desorb up to 5 wt % H(2) with an onset temperature of ~270 °C, which is significantly less than the desorption temperature of hydrogenated fullerenes (C(60)H(x)) and pure lithium hydride (decomposition temperature 500-600 and 670 °C respectively). However, our Li(x)-C(60)-H(y) system does not suffer from the same drawbacks as typical hydrogenated fullerenes (high desorption T and release of hydrocarbons) because the fullerene cage remains mostly intact and is only slightly modified during multiple hydrogen desorption/absorption cycles. We also observed a reversible phase transition of C(60) in the material from face-centered cubic to body-centered cubic at high levels of hydrogenation.

Machine learning-assisted crystal engineering of a zeolite.

It is shown that Machine Learning (ML) algorithms can usefully capture the effect of crystallization composition and conditions (inputs) on key microstructural characteristics (outputs) of faujasite type zeolites (structure types FAU, EMT, and their intergrowths), which are widely used zeolite catalysts and adsorbents. The utility of ML (in particular, Geometric Harmonics) toward learning input-output relationships of interest is demonstrated, and a comparison with Neural Networks and Gaussian Process Regression, as alternative approaches, is provided. Through ML, synthesis conditions were identified to enhance the Si/Al ratio of high purity FAU zeolite to the hitherto highest level (i.e., Si/Al = 3.5) achieved via direct (not seeded), and organic structure-directing-agent-free synthesis from sodium aluminosilicate sols. The analysis of the ML algorithms' results offers the insight that reduced Na2O content is key to formulating FAU materials with high Si/Al ratio. An acid catalyst prepared by partial ion exchange of the high-Si/Al-ratio FAU (Si/Al = 3.5) exhibits improved proton reactivity (as well as specific activity, per unit mass of catalyst) in propane cracking and dehydrogenation compared to the catalyst prepared from the previously reported highest Si/Al ratio (Si/Al = 2.8).

Pressure and temperature dependence of the decomposition pathway of LiBH4.

The decomposition pathway is crucial for the applicability of LiBH(4) as a hydrogen storage material. We discuss and compare the different decomposition pathways of LiBH(4) according to the thermodynamic parameters and show the experimental ways to realize them. Two pathways, i.e. the direct decomposition into boron and the decomposition via Li(2)B(12)H(12), were realized under appropriate conditions, respectively. By applying a H(2) pressure of 50 bar at 873 K or 10 bar at 700 K, LiBH(4) is forced to decompose into Li(2)B(12)H(12). In a lower pressure range of 0.1 to 10 bar at 873 K and 800 K, the concurrence of both decomposition pathways is observed. Raman spectroscopy and (11)B MAS NMR measurements confirm the formation of an intermediate Li(2)B(12)H(12) phase (mostly Li(2)B(12)H(12) adducts, such as dimers or trimers) and amorphous boron.

Magnesium borohydride: from hydrogen storage to magnesium battery.

Beyond hydrogen storage: The first example of reversible magnesium deposition/stripping onto/from an inorganic salt was seen for a magnesium borohydride electrolyte. High coulombic efficiency of up to 94 % was achieved in dimethoxyethane solvent. This Mg(BH(4))(2) electrolyte was utilized in a rechargeable magnesium battery.

Delamination of layered zeolite precursors under mild conditions: synthesis of UCB-1 via fluoride/chloride anion-promoted exfoliation.

New material UCB-1 is synthesized via the delamination of zeolite precursor MCM-22 (P) at pH 9 using an aqueous solution of cetyltrimethylammonium bromide, tetrabutylammonium fluoride, and tetrabutylammonium chloride at 353 K. Characterization by powder X-ray diffraction, transmission electron microscopy, and nitrogen physisorption at 77 K indicates the same degree of delamination in UCB-1 as previously reported for delaminated zeolite precursors, which require a pH of greater than 13.5 and sonication in order to achieve exfoliation. UCB-1 consists of a high degree of structural integrity via (29)Si MAS NMR and Fourier transform infrared spectroscopies, and no detectable formation of amorphous silica phase via transmission electron microscopy. Porosimetry measurements demonstrate a lack of hysteresis in the N(2) adsorption/desorption isotherms and macroporosity in UCB-1. The new method is generalizable to a variety of Si:Al ratios and leads to delaminated zeolite precursor materials lacking amorphization.

Palladium catalysts for dehydrogenation of ammonia borane with preferential B-H activation.

Cationic Pd(II) complexes catalyzed the dehydrogenation of ammonia borane in the most efficient manner with the release of 2.0 equiv of H(2) in less than 60 s at 25 degrees C. Most of the hydrogen atoms were obtained from the boron atom of the ammonia borane. The first step of the dehydrogenation reaction was elaborated using density functional theory calculations.

Diquaternary ammonium compounds in zeolite synthesis: cyclic and polycyclic N-heterocycles connected by methylene chains.

An additional dimension has been added to our long-standing studies in high silica zeolite synthesis via a guest/host synergism. We have created and studied the impact of making symmetric diquaternary ammonium compounds, by varying the chain length between nitrogen charge centers, and the heterocycle size and geometry containing the nitrogen. This allows the introduction of a second spatial parameter in the use of the charged organo-cation guest in the zeolite synthesis. The series of 15 diquaternary ammonium compounds (5 heterocycles synthesized onto chain lengths of C4-C6) were tested in a total of 135 zeolite syntheses reactions. Nine screening reactions were employed for each guest molecule, and the conditions built upon past successes in finding novel high silica zeolites via introduction of boron, aluminum, or germanium as substituting tetrahedral framework atoms for silicon. Eighteen different zeolite structures emerged from the studies. The use of specific chain lengths for derivatives of the pyrrolidine ring system produced novel zeolite materials SSZ-74 and 75.