An evaluation of resolution, accuracy, and precision in FT-IR spectroscopy.

Infrared spectroscopy is a foundational technique for the elucidation of chemical structures. The advancements in interferometric spectroscopy, and specifically the development of Fourier transform infrared (FT-IR) spectroscopy, are responsible for the widespread usage of IR spectrometers ranging from teaching labs to pharmaceutical quality control. FT-IR affords an excellent signal-to-noise ratio that permits sensitive sampling with quantitative accuracy and high wavenumber precision based on well documented advantages (Jacquinot, Fellgett, Connes).

Sensitizing Explosives Through Molecular Doping.

Cocrystallization assembles multicomponent crystals in defined ratios that are held together by intermolecular interactions. While cocrystals have seen extensive use in the pharmaceutical industry for solving issues with stability and solubility, extension to the field of energetic materials for improved properties has proven difficult. Predicting successful coformers remains a challenge for systems lacking well-understood synthons that promote reliable intermolecular assembly.

Progress in Predicting Ionic Cocrystal Formation: The Case of Ammonium Nitrate.

In contrast to the mature predictive frameworks applied to neutral cocrystals, ionic cocrystals, those including an ion pair, are difficult to design. Furthermore, they are generally excluded categorically from studies which correlate specific molecular properties to cocrystal formation, leaving the prospective ionic cocrystal engineer with few clear avenues to success. Herein ammonium nitrate, an energetic oxidizing salt, is targeted for cocrystallization in a potential coformer group selected based on likely interactions with the nitrate ion as revealed in the Cambridge Structural Database; six novel ionic cocrystals were discovered.

Catalytic intramolecular aminoarylation of unactivated alkenes with aryl sulfonamides.

Arylethylamines are abundant motifs in myriad natural products and pharmaceuticals, so efficient methods to synthesize them are valuable in drug discovery. In this work, we disclose an intramolecular alkene aminoarylation cascade that exploits the electrophilicity of a nitrogen-centered radical to form a C-N bond, then repurposes the nitrogen atom's sulfonyl activating group as a traceless linker to form a subsequent C-C bond. This photoredox catalysis protocol enables the preparation of densely substituted arylethylamines from commercially abundant aryl sulfonamides and unactivated alkenes under mild conditions.

Total Synthesis of (+)-Cochlearol B by an Approach Based on a Catellani Reaction and Visible-Light-Enabled [2+2] Cycloaddition.

A 14-step synthesis of (+)-cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate.

Hydrazone and Oxime Olefination via Ruthenium Alkylidenes.

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR , OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes.

1- and 2-Azetines via Visible Light-Mediated [2 + 2]-Cycloadditions of Alkynes and Oximes.

Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development but remain underexplored due to challenges associated with their synthesis. We report an efficient, visible light-mediated approach toward 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular [2 + 2]-cycloaddition via triplet energy transfer from a commercially available iridium photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process.

Halogen Bonding Propensity in Solution: Direct Observation and Computational Prediction.

Halogen-bonded complexes are often designed by consideration of electrostatic potential (ESP) predictions. ESP predictions do not capture the myriad variables associated with halogen bond (XB) donors and acceptors; thus, binding interaction cannot be quantitatively predicted. Here, a discrepancy between predictions based on ESP energy difference (ΔV ) and computed gas phase binding energy (ΔE ) motivated the experimental determination of the relative strength of halogen bonding interactions in solution by Raman spectroscopic observation of complexes formed from interacting five iodobenzene-derived XB donors and four pyridine XB acceptors.

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide-alkyne cycloaddition.

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide-alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes.

Arene dearomatization through a catalytic N-centered radical cascade reaction.

Arene dearomatization reactions are an important class of synthetic technologies for the rapid assembly of unique chemical architectures. Herein, we report a catalytic protocol to initiate a carboamination/dearomatization cascade that proceeds through transient sulfonamidyl radical intermediates formed from native sulfonamide N-H bonds leading to 1,4-cyclohexadiene-fused sultams. Importantly, this work demonstrates a facile approach to employ two-dimensional aromatic compounds as modular building blocks to generate richly substituted, three-dimensional compounds.

Lewis acid-catalyzed carbonyl-olefin metathesis.

Catalytic carbonyl-olefin metathesis reactions enable direct carbon-carbon bond formation between carbonyl and olefin substrates relying on carbonyl-activation with a suitable Lewis acid. Based on this reaction design principle, efficient protocols for intermolecular carbonyl-olefin metathesis, as well as ring-closing and ring-opening carbonyl-olefin metathesis have been developed.

Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide.

The 60-year history of sodium diisopropylamide (NaDA) is described herein. We review various preparations, solvent-dependent stabilities, and solution structures. Synthetic applications of NaDA reported to date are framed by a mechanism-driven approach, emphasizing selectivities when appropriate.

Biocatalytic synthesis of α-amino ketones.

Stereospecific generation of α-amino ketones from common α-amino acids is difficult to achieve, often employing superstoichiometric alkylating reagents and requiring multiple protecting group manipulations. In contrast, the α-oxoamine synthase protein family performs this transformation stereospecifically in a single step without the need for protecting groups. Herein, we detail the characterization of the 8-amino-7-oxononanoate synthase (AONS) domain of the four-domain polyketide-like synthase SxtA, which natively mediates the formation of the ethyl ketone derivative of arginine.

Copper-Mediated Aminoquinoline-Directed Radiofluorination of Aromatic C-H Bonds with K F.

A Cu-mediated ortho-C-H radiofluorination of aromatic carboxylic acids that are protected as 8-aminoquinoline benzamides is described. The method uses K F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARβ2 agonist [ F]AC261066.

3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis.

Herein, we describe the development of a synthetic strategy towards chiral 3-pyrrolines based on the design principle of iron(III)-catalyzed carbonyl-olefin metathesis. This approach takes advantage of commercially available amino acids as chiral pool reagents and FeCl as a Lewis acid catalyst. Our strategy is characterized by its operational simplicity, mild reaction conditions and functional group tolerance.

Electrocatalytic CO reduction by a cobalt bis(pyridylmonoimine) complex: effect of acid concentration on catalyst activity and stability.

A Co complex with a redox-active bis(pyridylmonoimine) ligand has been prepared and shows catalytic activity for electrochemical CO reduction in acetonitrile. Addition of a proton source such as water or trifluoroethanol dramatically improves the activity and stability of the molecular catalyst. The Co complex reduces CO to CO selectively at -1.

Incremental full configuration interaction.

The incremental expansion provides a polynomial scaling method for computing electronic correlation energies. This article details a new algorithm and implementation for the incremental expansion of full configuration interaction (FCI), called iFCI. By dividing the problem into n-body interaction terms, accurate correlation energies can be recovered at low n in a highly parallel computation.

Iron-Catalyzed Oxyfunctionalization of Aliphatic Amines at Remote Benzylic C-H Sites.

We report the development of an iron-catalyzed method for the selective oxyfunctionalization of benzylic C(sp(3))-H bonds in aliphatic amine substrates. This transformation is selective for benzylic C-H bonds that are remote (i.e.

De Novo Design of Metalloproteins and Metalloenzymes in a Three-Helix Bundle.

For more than two decades, de novo protein design has proven to be an effective methodology for modeling native proteins. De novo design involves the construction of metal-binding sites within simple and/or unrelated α-helical peptide structures. The preparation of α3D, a single polypeptide that folds into a native-like three-helix bundle structure, has significantly expanded available de novo designed scaffolds.

Highly functionalizable penta-coordinate iron hydrogen production catalysts with low overpotentials.

Penta-coordinate iron carbonyl complexes that are built around the rigid Fe(PNP) motif (PNP = (C6H5)2PN(R)P(C6H5)2) are synthesized and structurally and spectroscopically characterized. These complexes allow for facile customization of the secondary ligand sphere with various types of linkers and functional groups. The new [Fe(S2C6H4)(PNP)(CO)] complexes show dihydrogen production electrocatalysis at overpotentials of 0.

Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors.

A 7-step synthesis of pharbinilic acid, a member of the gibberellin family of natural products and the first naturally occurring allogibberic acid, is reported. An efficient decarboxylative aromatization reaction enables the synthesis of pharbinilic acid and related analogs for evaluation as modulators of NF-κB activity. Remarkably, one analog displays a 2 μM IC50 in an NF-κB activity assay and inhibits an endogenous NF-κB-regulated pathway.

Sculpting Metal-binding Environments in Designed Three-helix Bundles.

protein design is a biologically relevant approach used to study the active centers of native metalloproteins. In this review, we will first discuss the design process in achieving αD, a designed three-helix bundle peptide with a well-defined fold. We will then cover our recent work in functionalizing the αD framework by incorporating a tris(cysteine) and tris(histidine) motif.

{RuNO}(6)vs. co-ligand oxidation: two non-innocent groups in one ruthenium nitrosyl complex.

Recently, a new {RuNO}(6) complex, [Ru(L)(PPh3)(NO)(Cl)](2+) (where L = 1-phenyl-1-(pyridin-2-yl)-2-(pyridin-2-ylmethylene)hydrazine), was reported which exhibits a one-electron quasireversible oxidation. The oxidized product, [Ru(L)(PPh3)(NO)(Cl)](3+), was isolated and proposed to be a highly unusual {RuNO}(5) complex. In this paper, we investigate the electronic structure of both of these ruthenium complexes by DFT calculations and find that the oxidized species is best described as a {RuNO}(6) complex with a co-ligand radical.

Amperometric nitric oxide sensors with enhanced selectivity over carbon monoxide via platinum oxide formation under alkaline conditions.

An improved planar amperometric nitric oxide (NO) sensor with enhanced selectivity over carbon monoxide (CO), which represents a volatile interfering species for NO sensors that has been largely overlooked until recently, is described. Formation of an oxide film on the inner platinum working electrode via anodic polarization using an inner alkaline electrolyte solution provides the basis for improved selectivity. Cyclic voltammetry reveals that formation of an oxidized Pt film inhibits adsorption of CO to the electrode surface, which is a necessary initial step in the electrocatalytic oxidation of CO on Pt.