Hyperpolarized 13C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in vivo Study

Hyperpolarized [1-¹³C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1-¹³C]fumarate metabolism using parahydrogen-induced polarization (PHIP), a low-cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost-effective and high-yield synthetic pathway of hydrogenation precursor [1-¹³C]acetylenedicarboxylate (ADC) was developed. The trans-selectivity of the hydrogenation reaction of ADC using a ruthenium-based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set-up was used to generate hyperpolarized [1-¹³C]fumarate at sufficient ¹³C polarization for ex vivo detection of hyperpolarized ¹³C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo ¹³C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.     

The Influence of Water Vapor on the Electrochemical Shift of an Ionic Liquid Measured by Ambient Pressure X-ray Photoelectron Spectroscopy

Ionic liquids (ILs) are considered to be one of the steppingstones to fabricate next generation electrochemical devices given their unique physical and chemical properties. The addition of water to ILs significantly impact electrochemical related properties including viscosity, density, conductivity, and electrochemical window. Herein we utilize ambient pressure X-ray photoelectron spectroscopy (APXPS) to examine the impact of water on values of the electrochemical shift (S), which is determined by measuring changes in binding energy shifts as a function of an external bias. APXPS spectra of C 1s, O 1s and N 1s regions are examined for the IL 1-butyl-3-methylimidazolium acetate, [C₄mim][OAc], at the IL/gas interface as a function of both water vapor pressure and external bias. Results reveal that in the absence of water vapor there is an IL ohmic drop between the working electrode and quasi reference electrode, giving rise to chemical specific S values of less than one. Upon introducing water vapor, S values approach one as a function of increasing water vapor pressure, indicating a decrease in the IL ohmic drop as the IL/water mixture becomes more conductive and the potential drop is driven by the electric double layer at the electrode/IL interface.     

Infrared and NMR Spectroscopic Fingerprints of the Asymmetric H7+O3 Complex in Solution

Infrared (IR) absorption in the 1000–3700 cm⁻¹ range and ¹H NMR spectroscopy reveal the existence of an asymmetric protonated water trimer, H₇⁺O_3, in acetonitrile. The core H₇⁺O₃ motif persists in larger protonated water clusters in acetonitrile up to at least 8 water molecules. Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations reveal irreversible proton transport promoted by propagating the asymmetric H₇⁺O₃ structure in solution. The QM/MM calculations allow for the successful simulation of the measured IR absorption spectra of H₇⁺O₃ in the OH stretch region, which reaffirms the assignment of the H₇⁺O₃ spectra to a hybrid-complex structure: a protonated water dimer strongly hydrogen-bonded to a third water molecule with the proton exchanging between the two possible shared-proton Zundel-like centers. The H₇⁺O₃ structure lends itself to promoting irreversible proton transport in presence of even one additional water molecule. We demonstrate how continuously evolving H₇⁺O₃ structures may support proton transport within larger water solvates.     

Dual-Metal Electrolytes for Hybrid-Ion Batteries: Synergism or Antagonism?

The construction of hybrid metal-ion batteries faces a plethora of challenges. A critical one is to unveil the solvation/desolvation processes at the molecular level in electrolytes that ensure efficient transfer of several types of charge carriers. This study reports first results on simulations of mixed-ion electrolytes. All combinations of homo- and hetero-binuclear complexes of Li⁺, Na⁺ and Mg²⁺, solvated with varying number of ethylene carbonate (EC) molecules are modeled in non-polar and polar environment by means of first principles calculations and compared to the mononuclear analogues in terms of stability, spatial organization, charge distribution and solvation/desolvation behavior. The used PF₆⁻ counterion is shown to have minor impact on the geometry of the complexes. The desolvation energy penalty of binuclear complexes can be lowered by the fluoride ions, emerging upon the PF₆⁻ decay. These model investigations could be extended to rationalize the solvation structure and ionic mobility in dual-ion electrolytes.     

Understanding the Chloride Affinity of Barbiturates for Anion Receptor Design

Due to their potential binding sites, barbituric acid (BA) and its derivatives have been used in metal coordination chemistry. Yet their abilities to recognize anions remain unexplored. In this work, we were able to identify four structural features of barbiturates that are responsible for a certain anion affinity. The set of coordination interactions can be finely tuned with covalent decorations at the methylene group. DFT-D computations at the BLYP-D3(BJ)/aug-cc-pVDZ level of theory show that the C−H bond is as effective as the N−H bond to coordinate chloride. An analysis of the electron charge density at the C−H⋅⋅⋅Cl⁻ and N−H⋅⋅⋅Cl⁻ bond critical points elucidates their similarities in covalent character. Our results reveal that the special acidity of the C−H bond shows up when the methylene group moves out of the ring plane and it is mainly governed by the orbital interaction energy. The amide and carboxyl groups are the best choices to coordinate the ion when they act together with the C−H bond. We finally show how can we use this information to rationally improve the recognition capability of a small cage-like complex that is able to coordinate NaCl.     

Magnetic Modulation in Heteroallene and Heterocumulene Based tert-butyl Nitroxide Diradicals: Spin Delocalization and Conformation Play Crucial Roles

We have theoretically investigated the magnetic properties of heteroallene (>C=C=X−) and heterocumulene (>C=C=C=X−) based tert-butyl nitroxide diradicals (X is P/As). Calculation of magnetic exchange coupling constant (J) shows ferromagnetic interaction in heteroallene based diradicals. Whereas, in heterocumulene based diradicals, tuning of J value from antiferro- to ferro-magnetic state is observed from Z- to E- isomer. Delocalization of spin density from radical site to the coupler (in planar arrangement) is observed in spin distribution analysis which is also advocated by molecular orbital analysis. The typical feature of tert-butyl nitroxide radical creates spin delocalization along with spin polarization within the coupler. The J values of all the diradicals strongly depend on the dihedral angle between radical center and coupler. Magneto-structural correlation shows that the change in dihedral angle tunes the magnetic property for both the Z- and E- isomers of heterocumulenes depending on the spin accumulation on two nearby magnetic centers. The extent of spin delocalization and conformation of spin centers on the molecular axis are important for the different J values observed in our designed systems.     

Biocomputing Based on DNA Strand Displacement Reactions

The high sequence specificity and precise base complementary pairing principle of DNA provides a rich orthogonal molecular library for molecular programming, making it one of the most promising materials for developing bio-compatible intelligence. In recent years, DNA has been extensively studied and applied in the field of biological computing. Among them, the toehold-mediated strand displacement reaction (SDR) with properties including enzyme free, flexible design and precise control, have been extensively used to construct biological computing circuits. This review provides a systemic overview of SDR design principles and the applications. Strategies for designing DNA-only, enzymes-assisted, other molecules-involved and external stimuli-controlled SDRs are described. The recently realized computing functions and the application of DNA computing in other fields are introduced. Finally, the advantages and challenges of SDR-based computing are discussed.     

Twist-Bend Nematic Glasses: The Synthesis and Characterisation of Pyrene-based Nonsymmetric Dimers

A selection of pyrene-based liquid crystal dimers have been prepared, containing either methylene-ether or diether linked spacers of varying length and parity. All the diether linked materials, CBOnO.Py (n=5, 6, 11, 12), exhibit conventional nematic and smectic A phases, with the exception of CBO11O.Py which is exclusively nematic. The methylene-ether linked dimer, CBnO.Py, with an even-membered spacer (n=5) was solely nematogenic, but odd-members (n=6, 8, 10) exhibited both nematic and twist-bend nematic phases. Replacement of the cyanobiphenyl fragment by cyanoterphenyl giving CT6O.Py, gave elevated melting and nematic-isotropic transition temperatures, and SmA and SmC_A phases were observed on cooling the nematic phase. Intermolecular face-to-face associations of the pyrene moieties drive glass formation, and all these materials have a glass transition temperature at or above room temperature. The stability of the glassy twist-bend nematic phase allowed for its study using AFM, and the helical pitch length, P_TB, was measured as 6.3 and 6.7 nm for CB6O.Py and CB8O.Py, respectively. These values are comparable to the shortest pitch of a twist-bend nematic phase measured to date.     

Rational Development of a Metal-Free Bifunctional System for the C−H Activation of Methane: A Density Functional Theory Investigation

The activation or heterolytic splitting of methane, a challenging substrate usually restricted to transition metals, has so far proven elusive in experimental frustrated Lewis pair (FLP) chemistry. In this article, we demonstrate, using density functional theory (DFT), that 1-aza-9-boratriptycene is a conceptually simple intramolecular FLP for the activation of methane. Systematic comparison with other FLP systems allows to gain insight into their reactivity with methane. The thermodynamics and kinetics of methane activation are interpreted by referring to the analysis of the natural charges and by employing the distortion-interaction/activation strain (DIAS) model. These showed that the nature of the Lewis base influences the selectivity over the reaction pathway, with N Lewis bases favoring the deprotonation mechanism and P bases the hydride abstraction one. The lower barrier of activation for 1-aza-9-boratriptycene and the higher products stability are due to a better interaction energy than its counterparts, itself due to electrostatic interactions with the methane moiety, favorable orbital overlaps allowed by the side-attack, and space proximity between the B and N atoms.     

Gelation Kinetics-Structure Analysis of pH-triggered Low Molecular Weight Hydrogelators

Properties such as shear modulus, gelation time, structure of supramolecular hydrogels are strongly dependent on self-assembly, gelation triggering mechanism and processes used to form the gel. In our work we extend reported rheology analysis methodologies to pH-triggered supramolecular gels to understand structural insight using a model system based on N−N’ Dibenzoyl-L-Cystine pH-triggered hydrogelator and Glucono-δ-Lactone as the trigger. We observed that Avrami growth model when applied to time-sweep rheological data of gels formed at lower trigger concentrations provide estimates of fractal dimension which agree well compared with visualization of the microstructure as seen via Confocal Laser Scanning Microscopy, for a range of gelator concentrations.