DDQ catalyzed oxidative lactonization of indole-3-butyric acids.

Benzylic C-H bonds next to electron rich aromatic rings are susceptible to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) promoted functionalization. In this work benzylic carbocations formed in this manner are trapped by a pendant carboxylic acid to form a lactone. Indole-3-butyric acids are especially good substrates for the reaction.

Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation.

The aim of the present study was to investigate how different polymers affect the dissociation of cocrystals prepared by co-spray-drying active pharmaceutical ingredient (API), coformer, and polymer. Diclofenac acid-l-proline cocrystal (DPCC) was selected in this study as a model cocrystal due to its previously reported poor physical stability in a high-humidity environment. Polymers investigated include polyvinylpyrrolidone (PVP), poly(1-vinylpyrrolidone--vinyl acetate) (PVPVA), hydroxypropyl methyl cellulose, hydroxypropylmethylcellulose acetate succinate, ethyl cellulose, and Eudragit L-100.

Synthetic studies on the indane SHIP1 agonist AQX-1125.

AQX-1125 is an indane based SHIP1 agonist that has been evaluated in the clinic for the treatment of bladder pain syndrome/interstitial cystitis. To support our own studies on SHIP1 agonists as potential treatments for IBD and Crohn's disease, a new synthetic route to the SHIP1 agonist AQX-1125 has been developed. This sequence utilizes a hydroxy-acid intermediate which allows for ready differentiation of the C6 and C7 positions.

Alkylation of isatins with trichloroacetimidates.

-Alkylation of isatins can be achieved utilizing trichloroacetimidate electrophiles and a Lewis acid catalyst. These reactions provide access to -alkyl isatins, versatile scaffolds which are often employed in the synthesis of pharmaceutical lead structures as well as natural products. Secondary trichloroacetimidates that are precursors to stabilized carbocations provided excellent yields of the isatin product.

Direct Observation of Anthracene Clusters at Ice Surfaces.

Heterogeneous processes can control atmospheric composition. Snow and ice present important, but poorly understood, reaction media that can greatly alter the composition of air in the cryosphere in polar and temperate regions. Atmospheric scientists struggle to reconcile model predictions with field observations in snow-covered regions due in part to experimental challenges associated with monitoring reactions at air-ice interfaces, and debate regarding reaction kinetics and mechanisms has persisted for over a decade.

Adaptive Recombinant Nanoworms from Genetically Encodable Star Amphiphiles.

Recombinant nanoworms are promising candidates for materials and biomedical applications ranging from the templated synthesis of nanomaterials to multivalent display of bioactive peptides and targeted delivery of theranostic agents. However, molecular design principles to synthesize these assemblies (which are thermodynamically favorable only in a narrow region of the phase diagram) remain unclear. To advance the identification of design principles for the programmable assembly of proteins into well-defined nanoworms and to broaden their stability regimes, we were inspired by the ability of topologically engineered synthetic macromolecules to acess rare mesophases.

New Insights into the Crystallographic Disorder in the Polymorphic Forms of Aspirin from Low-Frequency Vibrational Analysis.

Terahertz time-domain spectroscopy (THz-TDS) is applied to two polymorphs of acetylsalicylic acid (aspirin), and the experimental spectra are compared to lattice dynamical calculations using high accuracy density functional theory. The calculations confirm that forms I and II have very close energetic and thermodynamic properties and also that they show similar spectral features in the far-infrared region, reflecting the high degree of similarity in their crystal structures. Unique vibrational modes are identified for each polymorph which allow them to be distinguished using THz-TDS measurements.

Formation of Pyrroloindolines the Alkylation of Tryptamines with Trichloroacetimidates.

Pyrroloindolines and related systems are present in a large number of complex natural products. These core structures have generated considerable synthetic interest, as many of the compounds possess challenging, elaborate structures and interesting biological properties. Recently we have focused on using trichloroacetimidates for the synthesis of these fascinating molecules.

Tandem elimination-oxidation of tertiary benzylic alcohols with an oxoammonium salt.

Tertiary benzylic alcohols react with oxoammonium salts, undergoing a tandem elimination/allylic oxidation to provide an allylic ether product in a single step. This mode of reactivity provides a rapid entry into allylic ethers from certain benzylic tertiary alcohols. The allylic ether may be cleaved under reductive conditions to reveal the allylic alcohol.

PV[O]H: Noninvasive Enabling Technology, New Physiological Monitoring, and Big Data.

Introduction: Measures of normal and abnormal physiology are interrelated and vary continuously. Our ability to detect and predict changes in physiology in real time has been limited in part by the requirement for blood sampling and the lack of a continuous data stream of various "signals", i.e.

Non-canonical lipoproteins with programmable assembly and architecture.

The substrate promiscuity of an acyltransferase is leveraged to synthesize artificial lipoproteins bearing a non-canonical PTM (ncPTM). The non-canonical functionality of these lipoproteins results in a distinctive hysteretic assembly-absent from the canonical lipoproteins-and is used to prepare hybrid multiblock materials with precise and programmable patterns of amphiphilicity. This study demonstrates the promise of expanding the repertoire of PTMs for the development of nanomaterials with a unique assembly and function.

Post-Translational Modification Mimicry for Programmable Assembly of Elastin-Based Protein Polymers.

Post-translational modification (PTM) of protein polymers is emerging as a powerful bioinspired strategy to create protein-based hybrid materials with molecularly encoded assembly and function for applications in nanobiotechnology and medicine. While these modifications can be accomplished by harnessing native biological machinery (i.e.

Genetically Encoded Inverse Bolaamphiphiles.

Developing new protein-based materials with a programmable assembly is of great scientific interest and technological importance. Inspired by nature's use of post-translational modifications (PTMs) to control the function and location of proteins, we have leveraged lipidation-the PTM of proteins with lipids-to synthesize genetically encoded lipidated proteins with controllable hierarchical assembly. Specifically, we envisioned the combination of two orthogonal lipidation pathways with different regioselectivity and substrate preferences inside to produce recombinant nanomaterials with distinct lipidation domains at each terminus of proteins.

Quantitative Analysis of Minium and Vermilion Mixtures Using Low-Frequency Vibrational Spectroscopy.

Low-frequency vibrational spectroscopy offers a compelling solution for the nondestructive and noninvasive study of pigments in historical artifacts by revealing the characteristic sub-200 cm spectral features of component materials. The techniques of terahertz time-domain spectroscopy (THz-TDS) and low-frequency Raman spectroscopy (LFRS) are complementary approaches to accessing this spectral region and are valuable tools for artifact identification, conservation, and restoration. In this investigation of historical pigments, pure and mixed samples of minium (PbO) and vermilion (HgS) were studied using a combination of THz-TDS and LFRS experiments to determine the limits of detection (LOD) and quantitation (LOQ) for each compound with both methods.

Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines.

2-Substituted indoles may be directly transformed to 3,3-dialkyl indolenines with trichloroacetimidate electrophiles and the Lewis acid TMSOTf. These reactions provide rapid access to complex indolenines which are present in a variety of complex natural products and medicinally relevant small molecule structures. This method provides an alternative to the use of transition metal catalysis.

Friedel-Crafts Alkylation of Indoles with Trichloroacetimidates.

Substituted indole scaffolds are often utilized in medicinal chemistry as they regularly possess significant pharmacological activity. Therefore the development of simple, inexpensive and efficient methods for alkylating the indole heterocycle continues to be an active research area. Reported are reactions of trichloroacetimidate electrophiles and indoles to address the challenges of accessing alkyl decorated indole structures.

Emerging investigator series: spatial distribution of dissolved organic matter in ice and at air-ice interfaces.

Dissolved organic matter (DOM) is a common solute in snow and ice at Earth's surface. Its effects on reaction kinetics in ice and at air-ice interfaces can be large, but are currently difficult to quantify. We used Raman microscopy to characterize the surface and bulk of frozen aqueous solutions containing humic acid, sodium dodecyl sulfate (SDS), and citric acid at a range of concentrations and temperatures.

Ester Formation via Symbiotic Activation Utilizing Trichloroacetimidate Electrophiles.

Trichloroacetimidates are useful reagents for the synthesis of esters under mild conditions that do not require an exogenous promoter. These conditions avoid the undesired decomposition of substrates with sensitive functional groups that are often observed with the use of strong Lewis or Brønsted acids. With heating, these reactions have been extended to benzyl esters without electron-donating groups.

Mapping the polymorphic transformation gateway vibration in crystalline 1,2,4,5-tetrabromobenzene.

The thermosalient behavior of 1,2,4,5-tetrabromobenzene (TBB) is related to a temperature-induced polymorphic structural change. The mechanism behind the phase transition has been investigated in this work using low-frequency (10-250 cm) Raman spectroscopy and solid-state density functional theory simulations. Careful adjustments of the probing laser power permitted thermal control of the polymorph populations and enabled high-quality Raman vibrational spectra to be obtained for both the β (low temperature) and γ (high temperature) forms of TBB.

Anomalous Temperature Dependence of the Lowest-Frequency Lattice Vibration in Crystalline γ-Aminobutyric Acid.

Crystalline γ-aminobutyric acid (GABA) exhibits unusual thermal behavior in a low-frequency lattice vibration that occurs at 37.2 cm at 290 K but decreases dramatically by 34.0% when the sample is cooled to 78 K.

Methyl-rotation dynamics in metal-organic frameworks probed with terahertz spectroscopy.

In ZIF-8 and its cobalt analogue ZIF-67, the imidazolate methyl-groups, which point directly into the void space, have been shown to freely rotate - even down to cryogenic temperatures. Using a combination of experimental terahertz time-domain spectroscopy, low-frequency Raman spectroscopy, and state-of-the-art ab initio simulations, the methyl-rotor dynamics in ZIF-8 and ZIF-67 are fully characterized within the context of a quantum-mechanical hindered-rotor model. The results lend insight into the fundamental origins of the experimentally observed methyl-rotor dynamics, and provide valuable insight into the nature of the weak interactions present within this important class of materials.

Promoter free allylation of trichloroacetimidates with allyltributylstannanes under thermal conditions to access the common 1,1'-diarylbutyl pharmacophore.

1,1'-Diarylbutyl groups are a common pharmacophore found in many biologically active small molecules. To access these systems under mild conditions, the reaction of diarylmethyl trichloroacetimidates with allyltributylstannanes was explored. Simply heating allyltributylstannane with the trichloroacetimidate resulted in substitution of the imidate with an allyl group.

Synthesis of 1,1'-Diarylethanes and Related Systems by Displacement of Trichloroacetimidates with Trimethylaluminum.

Benzylic trichloroacetimidates are readily displaced by trimethylaluminum under Lewis acid promoted conditions to provide the corresponding methyl substitution product. This method is a convenient way to access 1,1'-diarylethanes and related systems, which play a significant role in medicinal chemistry, with a number of systems owing their biological activity to this functionality. Most benzylic substrates undergo ready displacement, with electron deficient systems being the exception.

Synthesis of N-Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids.

N-Substituted 3-amino-4-halopyridines are valuable synthetic intermediates, as they readily provide access to imidazopyridines and similar heterocyclic systems. The direct synthesis of N-substituted 3-amino-4-halopyridines is problematic, as reductive aminations and base-promoted alkylations are difficult in these systems. A high yielding deprotection/alkylation protocol mediated by trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate is described, providing access to a wide scope of N-substituted 3-amino-4-halopyridines.

Phosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer.

The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity.