Medium-bridged lactams: a new class of non-planar amides

Medium-bridged twisted lactams, in which a non-planar amide bond is achieved by incorporating the nitrogen atom at the bridgehead position in a medium-sized heterocycle, offer an attractive setting in which to study the properties of distorted amide linkages. This Emerging Area article will describe progress in the preparation and study of these compounds. This work shows that compounds containing an even moderately distorted amide bond display useful and unusual chemical properties while retaining a measure of stability that enables their study.     

General Olefin Synthesis by the Palladium‐Catalyzed Heck Reaction of Amides: Sterically Controlled Chemoselective N?C Activation

Metal‐catalyzed reactions of amides proceeding via metal insertion into the N CO bond are severely underdeveloped due to resonance stabilization of the amide bond. Herein we report the first Heck reaction of amides proceeding via highly chemoselective N CO cleavage catalyzed by Pd⁰ utilizing amide bond ground‐state destabilization. Conceptually, this transformation provides access to a myriad of metal‐catalyzed transformations of amides via metal insertion/decarbonylation.     

Chemometric detection of acetaminophen in pharmaceuticals by infrared spectroscopy combined with pattern recognition techniques: comparison of attenuated total reflectance-FTIR and Raman spectroscopy

This paper presents and discusses the building of discriminant models from attenuated total reflectance (ATR)-FTIR and Raman spectra that were constructed to detect the presence of acetaminophen in over-the-counter pharmaceutical formulations. The datasets, containing 11 spectra of pure substances and 21 spectra of various formulations, were processed by partial least squares (PLS) discriminant analysis. The models found in the present study coped greatly with the discrimination, and their quality parameters were acceptable. A root mean square error of cross-validation was in the 0.14-0.35 range, while a root mean square error of prediction was in the 0.20-0.56 range. It was found that standard normal variate preprocessing had a negligible influence on the quality of ATR-FTIR; in the Raman case, it lowered the prediction error by 2. The influence of variable selection with the uninformative variable elimination by PLS method was studied, and no further model improvement was found.     

Charge transfer bands in the Eu3+ luminescence excitation spectra of isomeric europium pyridine-dicarboxylates

A ligand-cation charge transfer band was observed in the region of 360–400 nm in the Eu³⁺ luminescence excitation spectrum of europium 3,4-pyridine-dicarboxylates, but was absent in the spectra of europium 2,6-and 2,3-pyridine-dicarboxylates. This band is due to noticeable energy transfer through a charge-transfer state formed owing to the high polarizability of the ligand in the former compound. Energy transfer through the excited ligand-lanthanide charge-transfer state can explain the well-known effect of luminescence quenching by redox-sensitive lanthanide ions.     

Radiative lifetimes and tensor polarizabilities of 1s4f 1 F and 1s5f 1 F level of He I

He atoms have been excited by Ne⁺ ion impact and the depolarization of the fluorescence lines at 668 nm and 492 nm by magnetic and electric fields has been studied. The Ne⁺ ion energy could be chosen such that pure cascade level crossing signals were observed. From the widths of magnetic depolarization signals the radiative lifetimes τ(1s4f ¹ F)=74(2) ns and τ(1s5f ¹ F)=133(5) ns have been determined. By investigating the electric field splitting of the magnetic depolarization signals the tensor polarizabilities ¦α _ten(1s4f ¹ F)¦=0.58(1) kHz/(V/cm)² and ¦α _ten(1s5f ¹ F)¦=4.2(1) kHz/(V/cm)² have been deduced. From the latter value a mean frequencyv(1s5g?1s5f)=14.4 GHz of the transitions between the levels of the 1s5f configuration and those of the 1s5g configuration has been derived.α _ten(1s4f ¹ F) depends sensitively on the singlet-triplet mixing in the 1s4f configuration and thus a mixing coefficient could be deduced for this configuration.     

Cascade-free lifetime measurements on the 1s3d-levels of He I

He-atoms have been excited using 35 keV-He⁺-ion-He-atom-collisions. Investigating the electric and magnetic depolarization of fluorescence light, cascade-free lifetime measurements on the 1s 3d ¹ D and³ D-levels of He I have been performed. From our measurements we deduced:τ(3¹ D)=(15.3±0.3)ns,τ(3³ D)=(14.2±0.6)ns.     

Ribosomal synthesis of dehydroalanine-containing peptides

Dehydroalanine is a nonproteinogenic amino acid, but it is a component of a wide variety of natural products with therapeutic activities. Indeed, this alpha,beta-unsaturated residue is a highly versatile building block due to its rigidifying effect on peptide backbones and its electrophilicity which allows site-specific thiol ligations of peptides with small molecules or proteins. To harness such versatility in genetically encoded, combinatorial peptide libraries, we report a simple and robust method for the ribosomal synthesis of dehydroalanine-containing peptides. Selenalysine, a selenium-containing lysine analogue, was recruited as a masked dehydroalanine equivalent. This residue is efficiently incorporated by a reconstituted Escherichia coli translation system at high fidelity and efficiency despite the presence of low levels of lysine. Mild oxidative conditions were used to convert selenalysine into dehydroalanine post-translationally. Using this method, we demonstrate the preparation of polyunsaturated and highly decorated peptides. This report is an important step toward the preparation and selection of large libraries of protein-reactive compounds with potential use as novel drugs or as analytical tools.     

A simple 1H NMR method for determining the σ-donor properties of N-heterocyclic carbenes

The σ-donor properties of NHC ligands (NHC?=?N-heterocyclic carbene) are crucial in controlling their interaction with transition metals, and as a consequence, to determine the selectivity and reactivity of NHCs in transition-metal-catalysis. Herein, we report a simple NMR method for estimating the σ-donor properties of NHC ligands based on a straightforward ¹H NMR measurement of ligand precursors. We present evaluation of σ-donating properties for a range of NHC ligands varied by structure and electronics that are relevant to transition-metal-catalysis. We expect that the simple measurement of σ-donating properties of NHCs, together with the known methods for evaluating sterics and π-backbonding, will enhance the understanding of the properties of NHCs in transition-metal-catalysis.     

Informational complexity and functional activity of RNA structures

Very little is known about the distribution of functional DNA, RNA, and protein molecules in sequence space. The question of how the number and complexity of distinct solutions to a particular biochemical problem varies with activity is an important aspect of this general problem. Here we present a comparison of the structures and activities of eleven distinct GTP-binding RNAs (aptamers). By experimentally measuring the amount of information required to specify each optimal binding structure, we show that defining a structure capable of 10-fold tighter binding requires approximately 10 additional bits of information. This increase in information content is equivalent to specifying the identity of five additional nucleotide positions and corresponds to an approximately 1000-fold decrease in abundance in a sample of random sequences. We observe a similar relationship between structural complexity and activity in a comparison of two catalytic RNAs (ribozyme ligases), raising the possibility of a general relationship between the complexity of RNA structures and their functional activity. Describing how information varies with activity in other heteropolymers, both biological and synthetic, may lead to an objective means of comparing their functional properties. This approach could be useful in predicting the functional utility of novel heteropolymers.