Stepwise basis set selection.

The computational cost of quantum chemical methods grows rapidly with increasing level of theory and basis set size. At increasing costs, higher accuracies can be reached, forcing a compromise between cost and accuracy for most molecular systems. Heats of reaction, however, are mostly determined by a subset of atoms that experience significant bonding and/or electronic changes.

Radicals in natural product synthesis.

Free radical intermediates have intrigued chemists since their discovery, and an ever-increasing appreciation for their unique reactivity has resulted in the widespread utilization of these species throughout the field of chemical synthesis. This is most evident from the recent surge in the application of intermolecular radical reactions that feature in complex molecule syntheses. This tutorial review will discuss the diverse methods utilized for radical generation and reactivity to form critical bonds in natural product total synthesis.

Nickel-Catalyzed Amination of Silyloxyarenes through C-O Bond Activation.

Silyloxyarenes were utilized as electrophilic coupling partners with amines in the synthesis of aniline derivatives. A diverse range of amine substrates were used, including cyclic or acyclic secondary amines, secondary anilines, and sterically hindered primary anilines. Additionally, a range of sterically hindered and unhindered primary aliphatic amines were employed, which have previously been challenging with other classes of aryl ether electrophiles.

The Influence of Chemical Modification on Linker Rotational Dynamics in Metal-Organic Frameworks.

The robust synthetic flexibility of metal-organic frameworks (MOFs) offers a promising class of tailorable materials, for which the ability to tune specific physicochemical properties is highly desired. This is achievable only through a thorough description of the consequences for chemical manipulations both in structure and dynamics. Magic angle spinning solid-state NMR spectroscopy offers many modalities in this pursuit, particularly for dynamic studies.

Nitric Oxide Release for Improving Performance of Implantable Chemical Sensors - A Review.

Over the last three decades, there has been extensive interest in developing chemical sensors that can provide real-time measurements of blood gases (oxygen, carbon dioxide, and pH), glucose/lactate, and potentially other critical care analytes in the blood of hospitalized patients. However, clot formation with intravascular sensors and foreign body response toward sensors implanted subcutaneously can cause inaccurate analytical results. Further, the risk of bacterial infection from any sensor implanted in the human body is another major concern.

Combining asymmetric PCR-based enzymatic amplification with silicon photonic microring resonators for the detection of lncRNAs from low input human RNA samples.

A method for quantifying biologically relevant long-non-coding RNAs by combining nucleic acid amplification via asymmetric polymerase chain reaction (PCR) with label-free PCR product detection using silicon photonic microring resonator arrays is described. This approach eliminates the need for fluorophores, which presents a limit for spectral multiplexing in conventional qPCR methods, and rather offers potential for much higher levels of plexity by spatially arraying capture probes. Here, we demonstrate the potential of this technique to detect two differentially expressed lncRNA transcripts and an internal control mRNA transcript in different commercial human tissue specimens, as well as in a glioblastoma cell line using only nanogram input amounts of total RNA.

Microfabricated Probes for Studying Brain Chemistry: A Review.

Probe techniques for monitoring in vivo chemistry (e.g., electrochemical sensors and microdialysis sampling probes) have significantly contributed to a better understanding of neurotransmission in correlation to behaviors and neurological disorders.

Fluorescence Correlation Spectroscopy with Photobleaching Correction in Slowly Diffusing Systems.

Fluorescence correlation spectroscopy (FCS) is a powerful tool to quantitatively study the diffusion of fluorescently labeled molecules. It allows in principle important questions of macromolecular transport and supramolecular aggregation in living cells to be addressed. However, the crowded environment inside the cells slows diffusion and limits the reservoir of labeled molecules, causing artifacts that arise especially from photobleaching and limit the utility of FCS in these applications.

Phenylamino derivatives of tris(2-pyridylmethyl)amine: hydrogen-bonded peroxodicopper complexes.

A series of copper complexes bearing new 6-substituted tris(2-pyridylmethyl)amine ligands (L) appended with NH(p-R-CH) groups (R = H, CF, OMe) were prepared. These ligands are electronically tunable (ΔE = 160 mV) and Cu(L) complexes react with oxygen to form hydrogen bonded (trans-1,2-peroxo)dicopper species.

Collision induced unfolding of isolated proteins in the gas phase: past, present, and future.

Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences.

Strong correlation in incremental full configuration interaction.

Incremental Full Configuration Interaction (iFCI) reaches high accuracy electronic energies via a many-body expansion of the correlation energy. In this work, the Perfect Pairing (PP) ansatz replaces the Hartree-Fock reference of the original iFCI method. This substitution captures a large amount of correlation at zero-order, which allows iFCI to recover the remaining correlation energy with low-order increments.

Recent Developments in Pd(0)-Catalyzed Alkene Carboheterofunctionalization Reactions.

This review summarizes recent developments in palladium-catalyzed alkene carboalkoxylation and carboamination reactions. New synthetic methods that have been reported in the past four years are described, along with mechanistic issues and the influence of mechanism on product stereochemistry. The applications of these transformations to the synthesis of natural products and other biologically relevant compounds are also discussed.

An "Iceberg" Coating Preserves Bulk Hydration Dynamics in Aqueous PEG Solutions.

Ultrafast picosecond time scale two-dimensional infrared (2D-IR) spectroscopy of a new water-soluble transition metal complex acting as a vibrational probe shows that over a range of concentration and poly(ethylene glycol) (PEG) molecular mass (2000, 8000, and 20000 Da) the time scale of the sensed hydration dynamics differs negligibly from bulk water (DO). PEG is well-known to establish a highly stable hydration shell because the spacing between adjacent ethereal oxygens nearly matches water's hydrogen-bonding network. Although these first-shell water molecules are likely significantly retarded, they present an interface to subsequent hydration shells and thus diminish the largely entropic perturbation to water's orientational dynamics.

Near-infrared luminescent metallacrowns for combined cell fixation and counter staining.

Cell fixation is an essential approach for preserving cell morphology, allowing the targeting and labelling of biomolecules with fluorescent probes. One of the key requirements for more efficient fluorescent labelling is the preservation of cell morphology, which usually requires a combination of several fixation techniques. In addition, the use of a counter stain is often essential to improve the contrast of the fluorescent probes.

Rapid Guest Exchange and Ultra-Low Surface Tension Solvents Optimize Metal-Organic Framework Activation.

Exploratory research into the critical steps in metal-organic framework (MOF) activation involving solvent exchange and solvent evacuation are reported. It is discovered that solvent exchange kinetics are extremely fast, and minutes rather days are appropriate for solvent exchange in many MOFs. It is also demonstrated that choice of a very low surface tension solvent is critical in successfully activating challenging MOFs.

Temperature Dependence of the Catalytic Two- versus Four-Electron Reduction of Dioxygen by a Hexanuclear Cobalt Complex.

The synthesis and characterization of a hexanuclear cobalt complex 1 involving a nonheme ligand system, L1, supported on a SnO stannoxane core are reported. Complex 1 acts as a unique catalyst for dioxygen reduction, whose selectivity can be changed from a preferential 4e/4H dioxygen-reduction (to water) to a 2e/2H process (to hydrogen peroxide) only by increasing the temperature from -50 to 25 °C. A variety of spectroscopic methods (Sn-NMR, magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), SQUID, UV-vis absorption, and X-ray absorption spectroscopy (XAS)) coupled with advanced theoretical calculations has been applied for the unambiguous assignment of the geometric and electronic structure of 1.

Functional Mononitrosyl Diiron(II) Complex Mediates the Reduction of NO to NO with Relevance for Flavodiiron NO Reductases.

Reaction of [Fe(N-Et-HPTB)(CHCOS)](BF) (1) with (NO)(BF) produces a nonheme mononitrosyl diiron(II) complex, [Fe(N-Et-HPTB)(NO)(DMF)](BF) (2). Complex 2 is the first example of a [Fe{Fe(NO)}] species and is also the first example of a mononitrosyl diiron(II) complex that mediates the reduction of NO to NO. This work describes the selective synthesis, detailed characterization and NO reduction activity of 2 and thus provides new insights regarding the mechanism of flavodiiron nitric oxide reductases.

Role of Anomalous Water Constraints in the Efficacy of Pharmaceuticals Probed by H Solid-State NMR.

Water plays a complex and central role in determining the structural and reactive properties in numerous chemical systems. In crystalline materials with structural water, the primary focus is often to relate hydrogen bonding motifs to functional properties such as solubility, which is highly relevant in pharmaceutical applications. Nevertheless, understanding the full electrostatic landscape is necessary for a complete structure-function picture.

Chemoselective ratiometric imaging of protein S-sulfenylation.

Here we report a ratiometric fluorescent probe for chemoselective conjugation to sulfenic acids in living cells. Our approach couples an α-fluoro-substituted dimedone to an aminonaphthalene fluorophore (F-DiNap), which upon sulfenic acid conjugation is locked as the 1,3-diketone, changing the fluorophore excitation. F-DiNap reacts with S-sulfenylated proteins at equivalent rates to current probes, but the α-fluorine substitution blocks side-reactions with biological aldehydes.

Variable-Velocity Traveling-Wave Ion Mobility Separation Enhancing Peak Capacity for Data-Independent Acquisition Proteomics.

High mass accuracy, data-dependent acquisition is the current standard method in mass spectrometry-based peptide annotation and quantification. In high complexity samples, limited instrument scan speeds often result in under-sampling. In contrast, all-ion data-independent acquisition methods bypass precursor selection, alternating high and low collision energies to analyze product and precursor ions across wide mass ranges.

Recent advances in protein analysis by capillary and microchip electrophoresis.

This review article describes the significant recent advances in the analysis of proteins by capillary and microchip electrophoresis during the period from mid-2014 to early 2017. This review highlights the progressions, new methodologies, innovative instrumental modifications, and challenges for efficient protein analysis in human specimens, animal tissues, and plant samples. The protein analysis fields covered in this review include analysis of native, reduced, and denatured proteins in addition to Western blotting, protein therapeutics and proteomics.

Synthesis of 2,3-Dihydrobenzofurans via the Palladium Catalyzed Carboalkoxylation of 2-Allylphenols.

A new Pd-catalyzed alkene carboalkoxylation strategy for the preparation of 2,3-dihydrobenzofurans is described. This method effects the coupling of readily available 2-allylphenol derivatives with aryl triflates to generate a wide range of functionalized 2,3-dihydrobenzofurans in good yields and diastereoselectivities (up to >20:1). Use of newly developed reaction conditions that promote -heteropalladation of the alkene is essential in order to generate products in high yield.

Stereocontrolled Synthesis of Amino-Substituted Carbocycles by Pd-Catalyzed Alkene Carboamination Reactions.

Amino-substituted alkylidenecyclopentanes were synthesized through a stereoselective intermolecular Pd-catalyzed alkene carboamination reaction between alkenyl triflates bearing a pendant alkene and exogenous amine nucleophiles. The reactions are effective with a range of different substrate combinations, and proceed with generally high diastereoselectivity. Use of (S)-tBuPhox as the ligand in reactions of achiral substrates provides enantioenriched products with up to 98.

Computational study of C(sp)-O bond formation at a Pd centre.

This report describes a computational study of C(sp)-OR bond formation from Pd complexes of general structure Pd(CHCMe-o-CH-C,C')(F)(OR)(bpy-N,N') (bpy = 2,2'-bipyridine). Dissociation of OR from the different octahedral Pd starting materials results in a common square-pyramidal Pd cation. An S2-type attack by OR (OR = phenoxide, acetate, difluoroacetate, and nitrate) then leads to C(sp)-OR bond formation.

Second sphere ligand modifications enable a recyclable catalyst for oxidant-free alcohol oxidation to carboxylates.

Modification of the classic terpyridine pincer ligand with pendent NHR (R = mesityl) groups provides enhanced activity and stability in Ru-catalyzed dehydrogenation catalysis. These second sphere modifications furnish highly active catalysts for the oxidant-free dehydrogenative oxidation of primary alcohols to carboxylates and facilitate catalyst recycling.