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Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.

The recognition of substituted phosphates underpins many processes including DNA binding, enantioselective catalysis, and recently template-directed rotaxane synthesis. Beyond ATP and a few commercial substrates, however, little is known about how substituents effect organophosphate recognition. Here, we examined alcohol substituents and their impact on recognition by cyanostar macrocycles. The organophosphates were disubstituted by alcohols of various chain lengths, dipropanol, dihexanol, and didecanol phosphate, each accessed using modular solid-phases syntheses. Based on the known size-selective binding of phosphates by π-stacked dimers of cyanostars, threaded [3]pseudorotaxanes were anticipated. While seen with butyl substituents, pseudorotaxane formation was disrupted by competitive OH···O–hydrogen bonding between both terminal hydroxyls and the anionic phosphate unit. Crystallography also showed formation of a backfolded propanol conformation resulting in an 8-membered ring and a perched cyanostar assembly. Motivated by established entropic penalties accompanying ring formation, we reinstated [3]pseudorotaxanes by extending the size of the substituent to hexanol and decanol. Chain entropy overcomes the enthalpically favored OH···O–contacts to favor random-coil conformations required for seamless, high-fidelity threading of dihexanol and didecanol phosphates inside cyanostars. These studies highlight how chain length and functional groups on phosphate’s substituents can be powerful design tools to regulate binding and control assembly formation during phosphate recognition.

The N2analogue phosphorus nitride (PN) was the first phosphorus-containing compound to be detected in the interstellar medium; however, this thermodynamically unstable compound has a fleeting existence on Earth. Here, we show that reductive coupling of iron(IV) nitride and molybdenum(VI) phosphide complexes assembles PN as a bridging ligand in a structurally characterized bimetallic complex. Reaction with C≡NtBu releases the mononuclear complex [(N3N)Mo—PN]−, N3N = [(Me3SiNCH2CH2)3N]3–), which undergoes light-induced linkage isomerization to provide [(N3N)Mo—NP]−, as revealed by photocrystallography. While structural and spectroscopic characterization, supported by electronic structure calculations, reveals the PN multiple bond character, coordination to molybdenum induces a nucleophilic character at the terminal atom of the PN/NP ligands. Indeed, the linkage isomers can be trapped in solution by reaction with a Rh(I) electrophile.

The electrochemistry of flavone (1) has been carefully investigated at glassy carbon cathodes in dimethylformamide containing 0.10 M tetra-n-butylammonium tetrafluoroborate as supporting electrolyte. In this medium, a cyclic voltammogram for a reduction of 1exhibits a reversible cathodic process (Epc= −1.58 V and Epa= −1.47 V vs SHE) that is followed by an irreversible cathodic peak (Epc= −2.17 V vs SHE). When water (5.0 M) is introduced into the medium, the first peak for 1becomes irreversible (Epc= −1.56 V vs SHE), and the second (irreversible) peak shifts to −2.07 V vs SHE. Bulk electrolyses of 1at −1.60 V vs SHE afford flavanone, 2′-hydroxychalcone, 2′-hydroxy-3-phenylpropionate, and two new compounds, namely (Z)-1,6-bis(2-hydroxyphenyl)-3,4-diphenylhex-3-ene-1,6-dione (D1) and (Z)-2,2′-(1,2-diphenylethene-1,2-bis(benzofuran-3(2H))-one) (D2), obtained in significant amounts, that were characterized by means of 1H and 13C NMR spectrometry as well as single-crystal X-ray diffraction. Along with the above findings, we have proposed a mechanism for the electroreduction of 1, which has been further corroborated by our quantum mechanical study.

A central theme of nanocrystal (NC) research involves synthesis of dimension-controlled NCs and studyof size-dependent scaling laws governing their optical, electrical, magnetic, and thermodynamic properties. Here, we describe the synthesis of monodisperse CdO NCs that exhibit high quality-factor (up to 5.5) mid-infrared (MIR) localized surface plasmon resonances (LSPR) and elucidate the inverse scaling relationship between carrier concentration and NC size. The LSPR wavelength is readily tunable between 2.4 and ∼6.0 μm by controlling the size of CdO NCs. Structural and spectroscopic characterization provide strong evidence that free electrons primarily originate from self-doping due to NC surface-induced nonstoichiometry. The ability to probe and to control NC stoichiometry and intrinsic defects will pave the way toward predictive synthesis of doped NCs with desirable LSPR characteristics.

The nitride ligand in iron(IV) complex PhB(MesIm)3Fe≡N reacts with excess H3SiPh to afford PhB(MesIm)3Fe(μ-H)3(SiHPh) as the major product, which has been structurally and spectroscopically characterized. Bulkier silane HaSiPh2provides iron(II) amido complex PhB(MesIm)3FeN(H)(SiHPh2) as the initial product of the reaction, with excess H2SiPh2affording diamagnetic PhB(MesIm)3Fe(μ-H)3(SiPh2) as the major product. Unobserved iron(II) hydride PhB(MesIm)3Fe–H is implicated as an intermediate in this reaction, as suggested by the results of the reaction between iron(II) amido PhB(MesIm)3FeN(H)tBu and H3SiPh, which provides PhB(MesIm)3Fe(H)(μ-H)2(Si(NHtBu)Ph) as the sole product.

ATP binding cassette transporter A1 (ABCA1) is a critical transporter that mediates cellular cholesterol efflux from macrophages to apolipoprotein A-I (ApoA-I). Therefore, increasing the expression level of ABCA1 is anti-atherogenic and ABCA1 expression upregulators have become novel choices for atherosclerosis treatment. In this study, a series of N-benzothiazolyl-2-benzenesulfonamides, based on the structure of WY06 discovered in our laboratory, were designed and synthesized as novel ABCA1 expression upregulators. Based on an in vitroABCA1 upregulatory cell model, ABCA1 upregulation of target compounds was evaluated. Compounds 6c, 6d, and 6ihave good upregulated ABCA1 expression activities, with EC50values of 0.97, 0.37, and 0.41 μM, respectively. A preliminary structure–activity relationship is summarized. Replacing the methoxy group on the benzothiazole moiety of WY06 with a fluorine or chlorine atom and exchanging the ester group with a cyano group resulted in more potent ABCA1 upregulating activity. Moreover, compound 6iincreased ABCA1 mRNA and protein expression and significantly promoted cholesterol efflux in RAW264.7 cells. In conclusion, N-benzothiazolyl-2-benzenesulfonamides were identified as novel ABCA1 expression upregulators.

The synthesis of a rigid macrobicyclic N,S lactam L1and a topologically favored in/in N,S cryptand L2are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam L1exhibits two distinct rotameric conformations (plus their enantiomeric counterparts) at 25 °C, as confirmed via NMR spectroscopy and computational analysis. Coalescence of the resonances of L1was observed at 115 °C, allowing for complete nuclei to frequency correlation. Combining computational investigations with experimental data, topological equilibria and relative energies/strain relating to the perturbation of the pore were determined. Due to the increased conformational strain of the N2S2template, the nitrogen lone pairs in L2elicit a unique transannular interaction, resulting in a thermodynamically favored in/in nephroidal racemate. The combination of preferred topology, steric relief, and electronic localization of L2induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol–1.

This study presents a thorough investigation of the performance comparison of three ensemble data assimilation (DA) methods, including the maximum likelihood ensemble filter (MLEF), the ensemble Kalman filter (EnKF), and the iterative EnKF (IEnKF), with respect to solution accuracy and computational efficiency for nonlinear problems. The convection–diffusion–reaction (CDR) problem is first tested, and then, the chaotic Lorenz 96 model is solved. Both linear and nonlinear observation operators are considered. The study demonstrates that MLEF consistently produces more accurate and efficient solution than the other two methods and provides more information on both states and their uncertainties. The IEnKF and MLEF are used to estimate model parameters and uncertainty in initial conditions using a nonlinear observation operator. The assimilation performance is assessed based on the quality metrics, such as the squared true error, the trace of the error covariance matrix, and the root-mean-square (RMS) error. Based on these DA performance assessments, MLEF demonstrates better convergence and higher accuracy. Results of the CDR problem show significant improvements in the estimate of model parameters and the solution accuracy by MLEF compared to the EnKF family. This study provides evidence supporting the choice of MLEF when solving large nonlinear problems.

A fourth-order accurate finite-volume method is presented for solving time-dependent hyperbolic systems of conservation laws on mapped grids that are adaptively refined in space and time. Novel considerations for formulating the semi-discrete system of equations in computational space are combined with detailed mechanisms for accommodating the adapting grids. These considerations ensure that conservation is maintained and that the divergence of a constant vector field is always zero (freestream-preservation property). The solution in time is advanced with a fourth-order Runge–Kutta method. A series of tests verifies that the expected accuracy is achieved in smooth flows and the solution of a Mach reflection problem demonstrates the effectiveness of the algorithm in resolving strong discontinuities. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (NPs) with a diameter of 21.6 nm were coated with poly(maleic acid-alt-1-octadecene) (PMAcOD) modified with grafted 5000 Da poly(ethyelene glycol) (PEG) or short ethylene glycol (EG) tails. The coating procedure utilizes hydrophobic interactions of octadecene and oleic acid tails, while the hydrolysis of maleic anhydride moieties as well as the presence of hydrophilic PEG (EG) tails allows the NP hydrophilicity. The success of the NP coating was found to be independent of the degree of grafting, which was varied between 20 and 80% of the −MacOD− units, but depended on the length of the grafted tail. The NP coating and hydrophilization did not occur when the modified copolymer contained 750 Da PEG tails independent of the grafting degree. To explain this phenomenon, the micellization of the modified PMAcOD copolymers in water was analyzed by small-angle X-ray scattering. The PMAcOD molecules with the grafted 750 Da PEG tails form compact noninteracting disklike micelles, whose stability apparently allows for no interactions with the NP hydrophobic shells. The PMAcOD containing the 5000 Da PEG and EG tails form much larger structures capable of an efficient coating of the NPs. The coated NPs were characterized using transmission electron microscopy, dynamic light scattering, ζ-potential measurements, and thermal gravimetry analysis. The latter method demonstrated that the presence of long PEG tails in modified PMAcOD allows the attachment of fewer macromolecules (by a factor of ∼20) compared with the case of nonmodified or EG-modified PMAcOD, emphasizing the importance of PEG tails in NP hydrophilization. The NPs coated with PMAcOD modified with 60% (toward all −MAcOD− units) of the 5000 PEG tails bear a significant negative charge and display good stability in buffers. Such NPs can be useful as magnetic cores for virus-like particle formation.

The vanadium–bistelluride complex, PNPVTe2 see picture, in which the terminal telluride units can act as leaving groups or protecting groups, is prepared by activation of elemental Te by V. The complex masks PNPVI or PNPVIII sources when exposed to oxidants such as azides and diphenyldiazomethane. Isocyanides promote elimination of one Te ligand to furnish a VIIIcomplex with a terminal telluride ligand.

Iron oxide nanoparticles (NPs) with diameters of 16.1, 20.5, and 20.8 nm prepared from iron oleate precursors were coated with poly(maleic acid- alt-1-octadecene) (PMAcOD). The coating procedure exploited hydrophobic interactions of octadecene and oleic acid tails while hydrolysis of maleic anhydride moieties allowed the NP hydrophilicity. The PMAcOD nanostructure in water and the PMAcOD-coated NPs were studied using transmission electron microscopy, ζ-potential measurements, small-angle X-ray scattering, and fluorescence measurements. The combination of several techniques suggests that independently of the iron oxide core and oleic acid shell structures, PMAcOD encapsulates NPs, forming stable hydrophilic shells which withstand absorption of hydrophobic molecules, such as pyrene, without shell disintegration. Moreover, the PMAcOD molecules are predominantly attached to a single NP instead of self-assembling into the PMAcOD disklike nanostructures or attachment to several NPs. This leads to highly monodisperse aqueous samples with only a small fraction of NPs forming large aggregates due to cross-linking by the copolymer macromolecules.

Adrenocorticotropin (ACTH) (1–10), an adrenocorticotropin hormone fragment, has been studied by molecular dynamics (MD) simulation in an NPT ensemble in an explicit dodecylphosphocholine (DPC) micelle. Two starting configurations of the peptide/micelle system, corresponding to the insertion and surface-binding modes, were used. A common equilibrated configuration, in which the peptide lies parallel to the micellar surface, was reached from both simulations. In the initial part of the simulations, distance restraints derived from NMR nuclear Overhauser enhancements were incorporated before the peptide reached an equilibrium configuration with respect to the micelle. Analyses of the trajectories from the subsequent free (unrestrained) MD simulation showed that ACTH (1–10) does not conform strictly to a helical structure. The loss of the helical structure is due to decreased intramolecular hydrogen bonding accompanied by an increase of hydrogen bonding between the amide protons of the peptide and the micellar head groups. However, the extent of the latter interaction is less pronounced than in the negatively charged SDS micelle. The final structure enhances the amphipathic nature of the peptide, facilitating better interactions at the water–hydrophobic interface. The primary hydrophobic interactions with the micelle came from the side chains of Met⁴, Phe⁷, and Trp⁹. All peptide bonds were either hydrated or were involved in intramolecular hydrogen bonding. The interactions with the DPC micelle, the conformation of the bound peptide, and the dynamics of the peptide, as revealed by the time correlation functions of the N—H bonds, were compared with those of the ACTH (1–10)/SDS system studied previously by MD simulations. © 2001 John Wiley & Sons, Inc. Biopolymers 58: 643–659, 2001

Three adrenocorticotropin hormone (ACTH) fragments (1–10, 1–24, and 11–24) have been studied in water and in sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC) micelles by nuclear magnetic resonance spectroscopy. The trans–cis isomerism at all three proline sites (at positions 12, 19, and 24) was found in the 11–24 segment of the peptide. The population of the cis isomers changes with the environment of the peptide. Specifically, the presence of the DPC micelle does not affect the trans–cis equilibrium in the 11–24 segment from that in water. In contrast, the presence of the SDS micelles decreases the population of the cis isomer at Pro²⁴, but increases its population at Pro¹² and Pro¹⁹. The effect of SDS micelles on the trans–cis equilibrium at these proline sites was discussed. Intermolecular nuclear Overhauser effect (NOE) correlations between the ACTH peptides and the micelles were observed. These correlations occurred only in the 1–10 segment of the peptides, and the hydrophobic side chains contributed most to the intermolecular NOE. The intermolecular NOE pattern corroborates the suggestion that the 1–10 segment of the ACTH peptides bind to these micelles via a surface-binding mode, with most of the interactions coming from the insertion of the hydrophobic side chains. © 2000 John Wiley & Sons, Inc. Biopoly 58: 20–32, 2001

Thoracic ectopic kidney with congenital diaphragmatic hernia is a rare congenital malformation. We report a case of right thoracic ectopic kidney associated with congenital diaphragmatic hernia in a 4-year-old girl. Chest X-ray indicated the right diaphragmatic distention and contrast-enhanced CT showed thoracic ectopic kidney. We chose thoracoscopic approach for a complete anatomical repair. The bottom of the lower lobe of the right lung adhered to the hernia sac. Right thoracic ectopic kidney was pushed into abdominal cavity and congenital diaphragmatic defect was closed. Postoperative hemodynamics and renal function were normal. We review similar literatures and summarize surgical experience.

Pulsed-field gradient diffusion has been used to study the binding of two tachykinin peptides, [Tyr⁸]-substance P (SP) and [Tyr⁰]-neurokinin A (NKA) to two membrane-mimicking micelles, dodecylphosphocholine, and sodium dodecylsulfate. The structure of these peptides bound to the micelles have also been studied by using two-dimensional nmr and restrained simulated annealing calculations. No major difference in the structures of each peptide in the two micellar media was found. The difference between the micelle-bound structure of [Tyr⁸]SP and that of SP was also minor. The longer helical conformation on the C-terminus for [Tyr⁰]NKA was observed, compared with that for NKA. The relationship between the difference in the biological potencies of [Tyr⁸]SP and SP and the differences in their structure, especially the interaction of the side chains of the two aromatic residues, and the difference in their binding affinities to membrane was discussed. In addition, differences between the result of restrained molecular dynamics simulations of [Tyr⁸]SP in the presence of an explicit micelle and the present results were observed and discussed. © 1999 John Wiley & Sons, Inc. Biopoly 50: 555–568, 1999

The temperature dependence of the partition of a neuropeptide, Substance P (SP), and its [Tyr⁸] analogue in a widely used membrane mimic, dodecylphosphocholine micelles, was studied by using a pulsed field gradient nmr diffusion technique. The partition coefficient was found to decrease when the temperature is increased, indicating a favorable (negative) enthalpy change upon partitioning of the peptides. Thermodynamic functions of the partitioning were determined. The enthalpy of partition ΔHpart, was found to be in the −2.5 to −3.0 kcal/mol range, which is between 2 and 3 times higher than the entropic term −TΔSpart. The free energy of partitioning is consistent with a model in which the SP peptides interact with the micelles mainly through the hydrophobic side chains of the residues Phe⁷, Phe⁸ (or Tyr⁸), Leu¹⁰, and Met¹¹, and without the insertion of a major portion of the peptide into the hydrophobic core of the micelles. © 1998 John Wiley & Sons, Inc. Biopoly 45: 395–403, 1998

The partition and structure of three adrenocorticotropic hormone peptides ACTH(1–10), ACTH(1–24), and ACTH(11–24) in water and in sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC) micelles were studied by 2D NMR and NMR gradient diffusion measurements. The diffusion rates, the NH chemical shifts, and the nuclear Overhauser effect patterns provided a coherent picture of binding of these peptides. All three peptides are significantly partitioned in the negatively charged SDS micelles and possess definite secondary structure, as opposed to random structures in water. For ACTH (1–24), the hydrophobic 1–10 segment is partitioned in DPC micelles, but the charged 11–24 segment prefers to remain in the aqueous region. ACTH(11–24) does not bind significantly to the DPC micelles. The binding of the ACTH peptides in these two widely used “membrane mimics” are substantially different from that in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers obtained by attenuated total reflection infrared spectroscopy and from our preliminary diffusion studies of the same peptides in POPC vesicles. This study showed that, in a given micellar medium, all corresponding segments of these peptides are located in the same membrane environment in the system, regardless of whether these segments exist by themselves or are attached to other segments. This result may contradict the membrane-compartments concept of Schwyzer, which suggests that ACTH(1–10) and ACTH(1–24) are located in different membrane compartments because they have different address segments, and consequently, bind to different receptors. The present results also suggest that the assumption that micelles are good membrane mimics should be carefully examined.

This paper describes a space-time parallel algorithm with space-time adaptive mesh refinement (AMR). AMR with subcycling is added to multigrid reduction-in-time (MGRIT) in order to provide solution efficient adaptive grids with a reduction in work performed on coarser grids. This algorithm is achieved by integrating two software libraries: XBraid (Parallel time integration with multigrid. https://computation.llnl.gov/projects/parallel-timeintegration-multigrid) and Chombo (Chombo software package for AMR applications—design document, 2014). The former is a parallel time integration library using multigrid and the latter is a massively parallel structured AMR library. Employing this adaptive space-time parallel algorithm is Chord (Comput Fluids 123:202–217, 2015), a computational fluid dynamics (CFD) application code for solving compressible fluid dynamics problems. For the same solution accuracy, speedups are demonstrated from the use of space-time parallelization over the time-sequential integration on Couette flow and Stokes’ second problem. On a transient Couette flow case, at least a 1.5×speedup is achieved, and with a time periodic problem, a speedup of up to 13.7×over the time-sequential case is obtained. In both cases, the speedup is achieved by adding processors and exploring additional parallelization in time. The numerical experiments show the algorithm is promising for CFD applications that can take advantage of the time parallelism. Future work will focus on improving the parallel performance and providing more tests with complex fluid dynamics to demonstrate the full potential of the algorithm.

Simulations of turbulent flow present challenges in terms of accuracy and affordability on modern highly-parallel computer architectures. A multigrid-reduction-in-time algorithm is used to provide a framework for separately evolving different scales of turbulence and for parallelizing the temporal domain, thereby increasing the concurrency. It is hypothesized that the space–time locality of the small scales of turbulence can be used to circumvent difficulties in applying temporal multigrid to flows dominated by inertial physics. For algorithms that fall well short of spectral accuracy (fourth-order is used in this work) attention must be paid to the accuracy of features on scales transferred between multigrid levels. Numerical experiments were performed using implicit large-eddy simulation. Results from applying the approach to an infinite-Reynolds number Taylor–Green flow and a double-shear flow at a Reynolds number of 11650 provide strong evidence that the approach has merit. The multigrid-reduction-in-time framework can be used to parallelize the temporal domain of a high-Reynolds-number turbulent flow and permit independent convergence of different scales. Establishing this foundation allows for future research in reducing the wall-clock time to solve turbulent flows while retaining the same accuracy as sequential solvers. Current performance results from parallelizing the temporal domain are not competitive with those from sequential-in-time methods. • Exploit the physics of turbulence for temporal parallelization of inertial flows. • Separate the convergence of turbulent scales using multigrid reduction in time. • Spatial filtering is essential for accurate transfer of scales between multigrid levels. [ABSTRACT FROM AUTHOR]