Electron microscopy studies on DNA recognition by DNA-PK

Advances in transmission electron microscopy coupled to increasingly powerful biocomputing techniques are opening enormous possibilities to understand the structure and function of complex biological processes performed by large multi-protein assemblies. This is an exciting time for electron microscopists because we can combine our efforts with X-ray crystallographers and NMR spectroscopists to reach the prospect of studying the structure and dynamics of the so-called ‘molecular machines’. One of these fascinating systems is the macromolecular complex formed around double-stranded DNA breaks (DSBs). Non-homologous end-joining (NHEJ) is the main DSBs repair pathway in mammalian cells, where a collection of proteins interact to rejoin two broken DNA ends. During NHEJ, DNA-dependent protein kinase (DNA-PK) binds damaged DNA with high affinity and acts as the main scaffold for other repair factors. Several studies have made use of the electron microscope to reveal the three-dimensional architecture of DNA-PK and the structural basis for the recognition of damaged DNA and the activation of DNA-PK's kinase activity.     

Three-component Ugi-Smiles couplings of cyclic imines

Cyclic imines react with isocyanides and electron-deficient phenols to afford N-aryl piperidines and pyrrolidines in good yields (Ugi-Smiles couplings of cyclic imines). The starting imines were formed by oxidation with N-chlorosuccinimide followed by a base-induced dehydrochlorination.     

Intramolecular Alkynylogous Mukaiyama Aldol Reaction Starting from Bicyclic Alkanones Tethered to Alkynyl Esters: Formal Total Synthesis of (±)‐Hamigeran B

Selecting the ring : tert‐Butyldimethylsilyltriflate (TBSOTf)/NEt₃ treatment of alkynyl esters tethered to bicycloalkanones leads to the formation of tricyclic allenoates with total diasteroselectivity at the ring junction. An intramolecular alkynylogous Mukaiyama aldol reaction promoted by a TBSOTf/NEt₃ dual activation is involved. This novel methodology was illustrated by a formal total synthesis of (±)‐hamigeran B.

     

Determination of the helical screw sense and side-group chirality of a synthetic chiral polymer from Raman optical activity

Splitting it up: Excellent agreement between the experimental and the quantum-chemically simulated Raman optical activity (ROA) spectrum of (+)-poly(trityl methacrylate) shows that the polymer backbone adopts a left-handed helical conformation while the trityl side groups display a left-handed propeller conformation. Thus ROA can be used to determine the complete structure of synthetic chiral polymers in solution.     

Enantioselective Synthesis of Acyclic Stereotriads Featuring Fluorinated Tetrasubstituted Stereocenters

Elaboration of enantioenriched complex acyclic stereotriads represents a challenge for modern synthesis even more when fluorinated tetrasubstituted stereocenters are targeted. We have been able to develop a simple strategy in a sequence of two unprecedented steps combining a diastereoselective aldol-Tishchenko reaction and an enantioselective organocatalyzed kinetic resolution. The aldol-Tishchenko reaction directly generates a large panel of acyclic 1,3-diols possessing a fluorinated tetrasubstituted stereocenter by condensation of fluorinated ketones with aldehydes under very mild basic conditions. The anti 1,3-diols featuring three contiguous stereogenic centers are generated with excellent diastereocontrol (typically >99 : 1 dr). Depending upon the precursors both diastereomers of stereotriads are accessible through this flexible reaction. Furthermore, from the obtained racemic scaffolds, development of an organocatalyzed kinetic resolution enabled to generate the desired enantioenriched stereotriads with excellent selectivity (typically er >95 : 5).     

Trapped interfacial redox introduces reversibility in the oxygen reduction reaction in a non-aqueous Ca2+ electrolyte

Electrochemical investigations of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) have been conducted in a Ca²⁺-containing dimethyl sulfoxide electrolyte. While the ORR appears irreversible, the introduction of a tetrabutylammonium perchlorate (TBAClO₄) co-salt in excess concentrations results in the gradual appearance of a quasi-reversible OER process. Combining the results of systematic cyclic voltammetry investigations, the degree of reversibility depends on the ion pair competition between Ca²⁺ and TBA⁺ cations to interact with generated superoxide (O₂⁻). When TBA⁺ is in larger concentrations, and large reductive overpotentials are applied, a quasi-reversible OER peak emerges with repeated cycling (characteristic of formulations without Ca²⁺ cations). In situ Raman microscopy and rotating ring-disc electrode (RRDE) experiments revealed more about the nature of species formed at the electrode surface and indicated the progressive evolution of a charge storage mechanism based upon trapped interfacial redox. The first electrochemical step involves generation of O₂⁻, followed primarily by partial passivation of the surface by Ca_xO_y product formation (the dominant initial reaction). Once this product matrix develops, the subsequent formation of TBA⁺--O₂⁻ is contained within the Ca_xO_y product interlayer at the electrode surface and, consequently, undergoes a facile oxidation reaction to regenerate O₂.

An interlayer product of oxygen reduction with Ca²⁺/TBA⁺ yields a quasi-reversible oxygen evolution reaction by inducing a trapped interfacial redox process.