ResearchPad - Physical and Theoretical Chemistry Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Engineered Sulfur-Resistant Catalyst System with an Assisted Regeneration Strategy for Lean-Burn Methane Combustion]]>


Catalytic combustion of methane, the main component of natural gas, is a challenge under lean‐burn conditions and at low temperatures owing to sulfur poisoning of the Pd‐rich catalyst. This paper introduces a more sulfur‐resistant catalyst system that can be regenerated during operation. The developed catalyst system lowers the barrier that has restrained the use of liquefied natural gas as a fuel in energy production.

<![CDATA[Synergistic Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones via N–C Cleavage of Imides]]>


An electrophilic, imide-based, visible-light-promoted photoredox/Ni-catalyzed cross-coupling reaction for the synthesis of aliphatic ketones has been developed. This protocol proceeds through N–C(O) bond activation, made possible through the lower activation energy for metal insertion into this bond due to delocalization of the lone pair of electrons on the nitrogen by electron-withdrawing groups. The operationally simple and mild cross-coupling reaction is performed at ambient temperature and exhibits tolerance for a variety of functional groups.

<![CDATA[Complexes of gold and imidazole formed in helium nanodroplets]]>

We have studied complexes of gold atoms and imidazole (C3N2H4) produced in helium nanodroplets.

<![CDATA[Tris(2-mercaptoimidazolyl)hydroborato Cadmium Thiolate Complexes, [TmBut]CdSAr: Thiolate Exchange at Cadmium in a Sulfur-Rich Coordination Environment]]>


A series of cadmium thiolate compounds that feature a sulfur-rich coordination environment, namely [TmBut]CdSAr, have been synthesized by the reactions of [TmBut]CdMe with ArSH (Ar = C6H4-4-F, C6H4-4-But, C6H4-4-OMe, and C6H4-3-OMe). In addition, the pyridine-2-thiolate and pyridine-2-selenolate derivatives, [TmBut]CdSPy and [TmBut]CdSePy have been obtained via the respective reactions of [TmBut]CdMe with pyridine-2-thione and pyridine-2-selone. The molecular structures of [TmBut]CdSAr and [TmBut]CdEPy (E = S or Se) have been determined by X-ray diffraction and demonstrate that, in each case, the [CdS4] motif is distorted tetrahedral and approaches a trigonal monopyramidal geometry in which the thiolate ligand adopts an equatorial position; [TmBut]CdSPy and [TmBut]CdSePy, however, exhibit an additional long-range interaction with the pyridyl nitrogen atoms. The ability of the thiolate ligands to participate in exchange was probed by 1H and 19F nuclear magnetic resonance (NMR) spectroscopic studies of the reactions of [TmBut]CdSC6H4-4-F with ArSH (Ar = C6H4-4-But or C6H4-4-OMe), which demonstrate that (i) exchange is facile and (ii) coordination of thiolate to cadmium is most favored for the p-fluorophenyl derivative. Furthermore, a two-dimensional EXSY experiment involving [TmBut]CdSC6H4-4-F and 4-fluorothiophenol demonstrates that degenerate thiolate ligand exchange is also facile on the NMR time scale.

<![CDATA[A fluorescent activatable probe for imaging intracellular Mg2+]]>

An BODIPY probe for detection and imaging of Mg2+ without interference from Ca2+ is described.

<![CDATA[Extending the Lifetime of Hyperpolarized Propane Gas through Reversible Dissolution]]>


Hyperpolarized (HP) propane produced by the parahydrogen-induced polarization (PHIP) technique has been recently introduced as a promising contrast agent for functional lung magnetic resonance (MR) imaging. However, its short lifetime due to a spin–lattice relaxation time T1 of less than 1 s in the gas phase is a significant translational challenge for its potential biomedical applications. The previously demonstrated approach for extending the lifetime of the HP propane state through long-lived spin states allows the HP propane lifetime to be increased by a factor of ∼3. Here, we demonstrate that a remarkable increase in the propane hyperpolarization decay time at high magnetic field (7.1 T) can be achieved by its dissolution in deuterated organic solvents (acetone-d6 or methanol-d4). The approximate values of the HP decay time for propane dissolved in acetone-d6 are 35.1 and 28.6 s for the CH2 group and the CH3 group, respectively (similar values were obtained for propane dissolved in methanol-d4), which are ∼50 times larger than the gaseous propane T1 value. Furthermore, we show that it is possible to retrieve HP propane from solution to the gas phase with the preservation of hyperpolarization.

<![CDATA[Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange]]>


Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that 15N-SABRE works more efficiently and on a wider range of substrates than 1H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T1 times of up to 12 minutes. Long T1 times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds.

<![CDATA[Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters]]>


Dimerization is a common feature among the members of the neurotransmitter:sodium symporter (NSS) family of membrane proteins. Yet, the effect of dimerization on the mechanism of action of NSS members is not fully understood. In this study, we examined the collective dynamics of two members of the family, leucine transporter (LeuT) and dopamine transporter (DAT), to assess the significance of dimerization in modulating the functional motions of the monomers. We used to this aim the anisotropic network model (ANM), an efficient and robust method for modeling the intrinsic motions of proteins and their complexes. Transporters belonging to the NSS family are known to alternate between outward-facing (OF) and inward-facing (IF) states, which enables the uptake and release of their substrate (neurotransmitter) respectively, as the substrate is transported from the exterior to the interior of the cell. In both LeuT and DAT, dimerization is found to alter the collective motions intrinsically accessible to the individual monomers in favor of the functional transitions (OF IF), suggesting that dimerization may play a role in facilitating transport.

<![CDATA[Revised RNA Dihedral Parameters for the Amber Force Field Improve RNA Molecular Dynamics]]> <![CDATA[Computation of Hemagglutinin Free Energy Difference by the Confinement Method]]>


Hemagglutinin (HA) mediates membrane fusion, a crucial step during influenza virus cell entry. How many HAs are needed for this process is still subject to debate. To aid in this discussion, the confinement free energy method was used to calculate the conformational free energy difference between the extended intermediate and postfusion state of HA. Special care was taken to comply with the general guidelines for free energy calculations, thereby obtaining convergence and demonstrating reliability of the results. The energy that one HA trimer contributes to fusion was found to be 34.2 ± 3.4kBT, similar to the known contributions from other fusion proteins. Although computationally expensive, the technique used is a promising tool for the further energetic characterization of fusion protein mechanisms. Knowledge of the energetic contributions per protein, and of conserved residues that are crucial for fusion, aids in the development of fusion inhibitors for antiviral drugs.

<![CDATA[Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human DNA Polymerase η]]> <![CDATA[Interdependence of Inhibitor Recognition in HIV-1 Protease]]>


Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1′ and S2′ subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. All-atom molecular dynamics simulations starting from these structures were performed and systematically analyzed in terms of atomic fluctuations, intermolecular interactions, and water structure. These analyses reveal that the S1′ subsite highly influences other subsites: the extension of the hydrophobic P1′ moiety results in 1) reduced van der Waals contacts in the P2′ subsite, 2) more variability in the hydrogen bond frequencies with catalytic residues and the flap water, and 3) changes in the occupancy of conserved water sites both proximal and distal to the active site. In addition, one of the monomers in this homodimeric enzyme has atomic fluctuations more highly correlated with DRV than the other monomer. These relationships intricately link the HIV-1 protease subsites and are critical to understanding molecular recognition and inhibitor binding. More broadly, the interdependency of subsite recognition within an active site requires consideration in the selection of chemical moieties in drug design; this strategy is in contrast to what is traditionally done with independent optimization of chemical moieties of an inhibitor.

<![CDATA[Aqueous NMR Signal Enhancement by Reversible Exchange in a Single Step Using Water-Soluble Catalysts]]>


Two synthetic strategies are investigated for the preparation of water-soluble iridium-based catalysts for NMR signal amplification by reversible exchange (SABRE). In one approach, PEGylation of a variant N-heterocyclic carbene provided a novel catalyst with excellent water solubility. However, while SABRE-active in ethanol solutions, the catalyst lost activity in >50% water. In a second approach, synthesis of a novel di-iridium complex precursor where the cyclooctadiene (COD) rings have been replaced by CODDA (1,2-dihydroxy-3,7-cyclooctadiene) leads to the creation of a catalyst [IrCl(CODDA)IMes] that can be dissolved and activated in water—enabling aqueous SABRE in a single step, without need for either an organic cosolvent or solvent removal followed by aqueous reconstitution. The potential utility of the CODDA catalyst for aqueous SABRE is demonstrated with the ∼(−)32-fold enhancement of 1H signals of pyridine in water with only 1 atm of parahydrogen.

<![CDATA[Charge Carrier Trapping Processes in RE2O2S (RE = La, Gd, Y, and Lu)]]>


Two different charge carrier trapping processes have been investigated in RE2O2S:Ln3+ (RE = La, Gd, Y, and Lu; Ln = Ce, Pr, and Tb) and RE2O2S:M (M = Ti4+ and Eu3+). Cerium, praseodymium and terbium act as recombination centers and hole trapping centers while host intrinsic defects provide the electron trap. The captured electrons released from the intrinsic defects recombine at Ce4+, Pr4+, or Tb4+ via the conduction band. On the other hand, Ti4+ and Eu3+ act as recombination centers and electron trapping centers while host intrinsic defects act as hole trapping centers. For these codopants we find evidence that recombination is by means of hole release instead of electron release. The released holes recombine with the trapped electrons on Ti3+ or Eu2+ and yield broad Ti4+ yellow-red charge transfer (CT) emission or characteristic Eu3+ 4f–4f emission. We will conclude that the afterglow in Y2O2S:Ti4+, Eu3+ is due to hole release instead of more common electron release.

<![CDATA[Gd3TCAS2: An Aquated Gd3+-Thiacalix[4]arene Sandwich Cluster with Extremely Slow Ligand Substitution Kinetics]]>


In aqueous solution, Gd3+ and thiacalix[4]arene-p-tetrasulfonate (TCAS) form the complex [Gd3TCAS2]7–, in which a trinuclear Gd3+ core is sandwiched by two TCAS ligands. Acid-catalyzed dissociation reactions, as well as transmetalation and ligand exchange with physiological concentrations of Zn2+ and phosphate, showed [Gd3TCAS2]7– to be extremely inert compared to other Gd complexes. Luminescence lifetime measurements of the Tb analogue Tb3TCAS2 allowed estimation of the mean hydration number q to be 2.4 per Tb ion. The longitudinal relaxivity of [Gd3TCAS2]7– (per Gd3+) was r1 = 5.83 mM–1 s–1 at 20 Hz (37 °C, pH 7.4); however, this relaxivity was limited by an extremely slow water exchange rate that was 5 orders of magnitude slower than the Gd3+ aqua ion. Binding to serum albumin resulted in no relaxivity increase owing to the extremely slow water exchange kinetics. The slow dissociation and water exchange kinetics of [Gd3TCAS2]7– can be attributed to the very rigid coordination geometry.

<![CDATA[Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA]]>


An experimentally well-studied model of RNA tertiary structures is a 58mer rRNA fragment, known as GTPase-associating center (GAC) RNA, in which a highly negative pocket walled by phosphate oxygen atoms is stabilized by a chelated cation. Although such deep pockets with more than one direct phosphate to ion chelation site normally include magnesium, as shown in one GAC crystal structure, another GAC crystal structure and solution experiments suggest potassium at this site. Both crystal structures also depict two magnesium ions directly bound to the phosphate groups comprising this controversial pocket. Here, we used classical molecular dynamics simulations as well as umbrella sampling to investigate the possibility of binding of potassium versus magnesium inside the pocket and to better characterize the chelation of one of the binding magnesium ions outside the pocket. The results support the preference of the pocket to accommodate potassium rather than magnesium and suggest that one of the closely binding magnesium ions can only bind at high magnesium concentrations, such as might be present during crystallization. This work illustrates the complementary utility of molecular modeling approaches with atomic-level detail in resolving discrepancies between conflicting experimental results.

<![CDATA[EPR and Structural Characterization of Water-Soluble Mn2+-Doped Si Nanoparticles]]>


Water-soluble poly(allylamine) Mn2+-doped Si (SiMn) nanoparticles (NPs) were prepared and show promise for biologically related applications. The nanoparticles show both strong photoluminescence and good magnetic resonance contrast imaging. The morphology and average diameter were obtained through transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM); spherical crystalline Si NPs with an average diameter of 4.2 ± 0.7 nm were observed. The doping maximum obtained through this process was an average concentration of 0.4 ± 0.3% Mn per mole of Si. The water-soluble SiMn NPs showed a strong photoluminescence with a quantum yield up to 13%. The SiMn NPs had significant T1 contrast with an r1 relaxivity of 11.1 ± 1.5 mM–1 s–1 and r2 relaxivity of 32.7 ± 4.7 mM–1 s–1 where the concentration is in mM of Mn2+. Dextran-coated poly(allylamine) SiMn NPs produced NPs with T1 and T2 contrast with a r1 relaxivity of 27.1 ± 2.8 mM–1 s–1 and r2 relaxivity of 1078.5 ± 1.9 mM–1 s–1. X-band electron paramagnetic resonance spectra are fit with a two-site model demonstrating that there are two types of Mn2+ in these NP’s. The fits yield hyperfine splittings (A) of 265 and 238 MHz with significant zero field splitting (D and E terms). This is consistent with Mn in sites of symmetry lower than tetrahedral due to the small size of the NP’s.

<![CDATA[Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference Potential while Retaining Accuracy of the Target Fine Model]]>


Proposed in this contribution is a protocol for calculating fine-physics (e.g., ab initio QM/MM) free-energy surfaces at a high level of accuracy locally (e.g., only at reactants and at the transition state for computing the activation barrier) from targeted fine-physics sampling and extensive exploratory coarse-physics sampling. The full free-energy surface is still computed but at a lower level of accuracy from coarse-physics sampling. The method is analytically derived in terms of the umbrella sampling and the free-energy perturbation methods which are combined with the thermodynamic cycle and the targeted sampling strategy of the paradynamics approach. The algorithm starts by computing low-accuracy fine-physics free-energy surfaces from the coarse-physics sampling in order to identify the reaction path and to select regions for targeted sampling. Thus, the algorithm does not rely on the coarse-physics minimum free-energy reaction path. Next, segments of high-accuracy free-energy surface are computed locally at selected regions from the targeted fine-physics sampling and are positioned relative to the coarse-physics free-energy shifts. The positioning is done by averaging the free-energy perturbations computed with multistep linear response approximation method. This method is analytically shown to provide results of the thermodynamic integration and the free-energy interpolation methods, while being extremely simple in implementation. Incorporating the metadynamics sampling to the algorithm is also briefly outlined. The application is demonstrated by calculating the B3LYP//6-31G*/MM free-energy barrier for an enzymatic reaction using a semiempirical PM6/MM reference potential. These modifications allow computing the activation free energies at a significantly reduced computational cost but at the same level of accuracy compared to computing full potential of mean force.

<![CDATA[Protein–Protein Interactions in Dilute to Concentrated Solutions: α-Chymotrypsinogen in Acidic Conditions]]>


Protein–protein interactions were investigated for α-chymotrypsinogen by static and dynamic light scattering (SLS and DLS, respectively), as well as small-angle neutron scattering (SANS), as a function of protein and salt concentration at acidic conditions. Net protein–protein interactions were probed via the Kirkwood–Buff integral G22 and the static structure factor S(q) from SLS and SANS data. G22 was obtained by regressing the Rayleigh ratio versus protein concentration with a local Taylor series approach, which does not require one to assume the underlying form or nature of intermolecular interactions. In addition, G22 and S(q) were further analyzed by traditional methods involving fits to effective interaction potentials. Although the fitted model parameters were not always physically realistic, the numerical values for G22 and S(q → 0) were in good agreement from SLS and SANS as a function of protein concentration. In the dilute regime, fitted G22 values agreed with those obtained via the osmotic second virial coefficient B22 and showed that electrostatic interactions are the dominant contribution for colloidal interactions in α-chymotrypsinogen solutions. However, as protein concentration increases, the strength of protein–protein interactions decreases, with a more pronounced decrease at low salt concentrations. The results are consistent with an effective “crowding” or excluded volume contribution to G22 due to the long-ranged electrostatic repulsions that are prominent even at the moderate range of protein concentrations used here (<40 g/L). These apparent crowding effects were confirmed and quantified by assessing the hydrodynamic factor H(q → 0), which is obtained by combining measurements of the collective diffusion coefficient from DLS data with measurements of S(q → 0). H(q → 0) was significantly less than that for a corresponding hard-sphere system and showed that hydrodynamic nonidealities can lead to qualitatively incorrect conclusions regarding B22, G22, and static protein–protein interactions if one uses only DLS to assess protein interactions.

<![CDATA[Influence of Structural Heterogeneity on Diffusion of CH4 and CO2 in Silicon Carbide-Derived Nanoporous Carbon]]>


We investigate the influence of structural heterogeneity on the transport properties of simple gases in a Hybrid Reverse Monte Carlo (HRMC) constructed model of silicon carbide-derived carbon (SiC-DC). The energy landscape of the system is determined based on free energy analysis of the atomistic model. The overall energy barriers of the system for different gases are computed along with important properties, such as Henry constant and differential enthalpy of adsorption at infinite dilution, and indicate hydrophobicity of the SiC-DC structure and its affinity for CO2 and CH4 adsorption. We also study the effect of molecular geometry, pore structure and energy heterogeneity considering different hopping scenarios for diffusion of CO2 and CH4 through ultramicropores using the Nudged Elastic Band (NEB) method. It is shown that the energy barrier of a hopping molecule is very sensitive to the shape of the pore entry. We provide evidence for the influence of structural heterogeneity on self-diffusivity of methane and carbon dioxide using molecular dynamics simulation, based on a maximum in the variation of self-diffusivity with loading. A comparison of the MD simulation results with self-diffusivities from quasi-elastic neutron scattering (QENS) measurements and, with macroscopic uptake-based low-density transport coefficients, reveals the existence of internal barriers not captured in MD simulation and QENS experiments. Nevertheless, the simulation and macroscopic uptake-based diffusion coefficients agree within a factor of 2–3, indicating that our HRMC model structure captures most of the important energy barriers affecting the transport of CH4 in the nanostructure of SiC-DC.