β-Amino Acids Reduce Ternary Complex Stability and Alter the Translation Elongation Mechanism.

Templated synthesis of proteins containing non-natural amino acids (nnAAs) promises to expand the chemical space available to biological therapeutics and materials, but existing technologies are still limiting. Addressing these limitations requires a deeper understanding of the mechanism of protein synthesis and how it is perturbed by nnAAs. Here we examine the impact of nnAAs on the formation and ribosome utilization of the central elongation substrate: the ternary complex of native, aminoacylated tRNA, thermally unstable elongation factor, and GTP.

Recovering true FRET efficiencies from smFRET investigations requires triplet state mitigation.

Single-molecule fluorescence resonance energy transfer (smFRET) methods employed to quantify time-dependent compositional and conformational changes within biomolecules require elevated illumination intensities to recover robust photon emission streams from individual fluorophores. Here we show that outside the weak-excitation limit, and in regimes where fluorophores must undergo many rapid cycles of excitation and relaxation, non-fluorescing, excitation-induced triplet states with lifetimes orders of magnitude longer lived than photon-emitting singlet states degrade photon emission streams from both donor and acceptor fluorophores resulting in illumination-intensity-dependent changes in FRET efficiency. These changes are not commonly taken into consideration; therefore, robust strategies to suppress excited state accumulations are required to recover accurate and precise FRET efficiency, and thus distance, estimates.

β-amino acids reduce ternary complex stability and alter the translation elongation mechanism.

Templated synthesis of proteins containing non-natural amino acids (nnAAs) promises to vastly expand the chemical space available to biological therapeutics and materials. Existing technologies limit the identity and number of nnAAs than can be incorporated into a given protein. Addressing these bottlenecks requires deeper understanding of the mechanism of messenger RNA (mRNA) templated protein synthesis and how this mechanism is perturbed by nnAAs.

Mapping the influence of ligand electronics on the spectroscopic and O sensitization characteristics of Pd(II) biladiene complexes bearing phenyl-alkynyl groups at the 2- and 18-positions.

Photodynamic therapy (PDT) is a promising treatment for certain cancers that proceeds sensitization of ground state O to generate reactive O. Classic macrocyclic tetrapyrrole ligand scaffolds, such as porphyrins and phthalocyanines, have been studied in detail for their O photosensitization capabilities. Despite their compelling photophysics, these systems have been limited in PDT applications because of adverse biological side effects.

Photoredox-Nickel Dual-Catalyzed -Alkylation of Secondary Nitroalkanes: Access to Sterically Hindered α-Tertiary Amines.

The preparation of tertiary nitroalkanes via the nickel-catalyzed alkylation of secondary nitroalkanes using aliphatic iodides is reported. Previously, catalytic access to this important class of nitroalkanes via alkylation has not been possible due to the inability of catalysts to overcome the steric demands of the products. However, we have now found that the use of a nickel catalyst in combination with a photoredox catalyst and light leads to much more active alkylation catalysts.

Elucidation of complex triplet excited state dynamics in Pd(II) biladiene tetrapyrroles.

Pd(II) biladienes have been developed over the last five years as oligotetrapyrrole complexes that support a rich triplet photochemistry. In this work, we have undertaken the first detailed photophysical interrogation of three homologous Pd(II) biladienes bearing different combinations of methyl- and phenyl-substituents on the frameworks' sp-hybridized -carbon (, the 10-position of the biladiene framework). These experiments have revealed unexpected excited-state dynamics that are dependent on the wavelength of light used to excite the biladiene.

Leveraging Baird aromaticity for advancement of bioimaging applications.

In this perspective, we highlight the recent progress in utilizing Baird aromatic species to improve fluorophore performance in microscopy and imaging applications. We specifically focus on the origins of the use of Baird aromaticity in fluorescence applications, the development of “self‐healing” fluorophores leveraging cyclooctatetraene’ Baird aromaticity, and where developments need to occur to optimize this technology.

Modelling Causal Factors of Unintentional Electromagnetic Emanations Compromising Information Technology Equipment Security.

Information technology equipment (ITE) processing sensitive information can have its security compromised by unintentional electromagnetic radiation. Appropriately assessing likelihood of a potential compromise relies on radio frequency (RF) engineering expertise-specifically, requiring knowledge of the associated causal factors and their interrelationships. Several factors that can cause unintentional electromagnetic emanations that can lead to the compromise of ITE have been found in the literature.

Blockchain and population health.

Background: Blockchain technology has made great strides in many industries but has yet to impact the world of public health. Population health issues such as outbreak surveillance and controlled substance tracking during emergencies all require a secure, easily accessible database. While the healthcare industry is typically slow to adapt to change, blockchain technology lends itself well to many healthcare issues.

Electrochemically Mediated Oxidation of Sensitive Propargylic Benzylic Alcohols.

The electrochemical oxidation of sensitive propargylic benzylic alcohols having varying substituents is reported. We describe the preparation and characterization of -hydroxytetrafluorophthalimide (TFNHPI) and pseudo-high-throughput development of a green electrochemical oxidation protocol for sensitive propargylic benzylic alcohols that employs TFNHPI as a stable electrochemical mediator. The electrochemical oxidation of propargylic benzylic alcohols was leveraged to develop short synthetic pathways for preparing gram quantities of resveratrol natural products such as pauciflorols.

Synthesis, Electrochemistry, and Photophysics of Pd(II) Biladiene Complexes Bearing Varied Substituents at the sp-Hybridized 10-Position.

A set of Pd(II) biladiene complexes bearing different combinations of methyl- and phenyl-substituents on the sp-hybridized -carbon (the 10-position of the biladiene framework) was prepared and studied. In addition to a previously described Pd(II) biladiene complex bearing geminal dimethyl substituents a the 10-position (), homologous Pd(II) biladienes bearing geminal methyl and phenyl substituents () and geminal diphenyl groups() were prepared and structurally characterized. Detailed electrochemical as well as steady-state and time-resolved spectroscopic experiments were undertaken to evaluate the influence of the substituents on the biladiene's tetrahedral -carbon.

Synthesis, Spectroscopic, and O Sensitization Characteristics of Extended Pd(II) 10,10-Dimethylbiladiene Complexes Bearing Alkynyl-Aryl Appendages.

Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues.

Synthesis, Redox, and Spectroscopic Properties of Pd(II) 10,10-Dimethylisocorrole Complexes Prepared via Bromination of Dimethylbiladiene Oligotetrapyrroles.

Two brominated 10,10-dimethylisocorrole (10-DMIC) derivatives containing Pd(II) centers have been prepared and characterized. These compounds were prepared via bromination of 10,10-dimethylbiladiene-based oligotetrapyrroles. Bromination of free base 10,10-dimethylbiladiene () followed by metalation with Pd(OAc), as well as bromination of the corresponding Pd(II) dimethylbiladiene complex () provide routes to Pd(II) hexabromo-10,10-dimethyl-5,15-bis(pentafluorophenyl)-isocorrole (]) and Pd(II) octabromo-10,10-dimethyl-5,15-bis(pentafluorophenyl)-isocorrole (]).

The Distinct Conformational Landscapes of 4S-Substituted Prolines That Promote an endo Ring Pucker.

4-Substitution on proline directly impacts protein main chain conformational preferences. The structural effects of N-acyl substitution and of 4-substitution were examined by NMR spectroscopy and X-ray crystallography on minimal molecules with a proline 4S-nitrobenzoate. The effects of N-acyl substitution on conformation were attenuated in the 4S-nitrobenzoate context, due to the minimal role of the n→π* interaction in stabilizing extended conformations.

pH-Driven Mechanistic Switching from Electron Transfer to Energy Transfer between [Ru(bpy)] and Ferrocene Derivatives.

The metal-to-ligand charge transfer excited states of [Ru(bpy)] (bpy = 2,2'-bipyridine) may be deactivated via energy transfer or electron transfer with ferrocene derivatives in aqueous conditions. Stern-Volmer quenching analysis revealed that the rate constant for [Ru(bpy)] excited-state quenching depends on solution pH when a ferrocenyl-amidinium derivative (Fc-am) containing a proton-responsive functionality tethered to the ferrocene center was present. By contrast, the rate constant with which the [Ru(bpy)] excited state is quenched by an analogous ferrocene derivative (ferrocenyl-trimethylammonium, Fc-mam) that lacks a protonic group does not depend on pH.

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

Background: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).