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).     

Physical,Thermal and Biological Properties of Yellow Dyes with Two Azodiphenylether Groups of Anthracene

Two yellow bis-azo dyes containing anthracene and two azodiphenylether groups (BPA and BTA) were prepared, and an extensive investigation of their physical, thermal and biological properties was carried out. The chemical structure was confirmed by the FTIR spectra, while from the UV–Vis spectra, the quantum efficiency of the laser fluorescence at the 476.5 nm was determined to be 0.33 (BPA) and 0.50 (BTA). The possible transitions between the energy levels of the electrons of the chemical elements were established, identifying the energies and the electronic configurations of the levels of transition. Both crystals are anisotropic, the optical phenomenon of double refraction of polarized light (birefringence) taking place. Images of maximum illumination and extinction were recorded when the crystals of the bis-azo compounds rotated by 90° each, which confirms their birefringence. A morphologic study of the thin films deposited onto glass surfaces was performed, proving the good adhesion of both dyes. By thermal analysis and calorimetry, the melting temperatures were determined (~224–225 °C for both of them), as well as their decomposition pathways and thermal effects (enthalpy variations during undergoing processes); thus, good thermal stability was exhibited. The interaction of the two compounds with collagen in the suede was studied, as well as their antioxidant activity, advocating for good chemical stability and potential to be safely used as coloring agents in the food industry.     

β-N-Heterocyclic Cyclobutane Carboximides: Synthesis through a Tandem Base-Catalyzed Amidation/aza-Michael Addition Protocol and Facile Transformations

A stereoselective one-pot double derivatization of cyclobutene-1-carboxylic acid via a mild organic base catalyzed amidation/aza-Michael addition of benzo[d]oxazol-2(3H)-ones has been developed. This unprecedented tandem reaction provides access to novel β-N-heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans-β-N-heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures.     

Isoguanine and 5‐Methyl‐Isocytosine Bases,In Vitro and In Vivo

The synthesis, base‐pairing properties and in vitro and in vivo characteristics of 5‐methyl‐isocytosine (isoC^Me) and isoguanine (isoG) nucleosides, incorporated in an HNA(h) (hexitol nucleic acid)–DNA(d) mosaic backbone, are described. The required h‐isoG phosphoramidite was prepared by a selective deamination as a key step. As demonstrated by T_m measurements the hexitol sugar showed slightly better mismatch discrimination against dT. The d‐isoG base mispairing follows the order T>G>C while the h‐isoG base mispairing follows the order G>C>T. The h‐ and d‐isoC^Me bases mainly mispair with G. Enzymatic incorporation experiments show that the hexitol backbone has a variable effect on selectivity. In the enzymatic assays, isoG misincorporates mainly with T, and isoC^Me misincorporates mainly with A. Further analysis in vivo confirmed the patterns of base‐pair interpretation for the deoxyribose and hexitol isoC^Me/isoG bases in a cellular context, through incorporation of the bases into plasmidic DNA. Results in vivo demonstrated that mispairing and misincorporation was dependent on the backbone scaffold of the base, which indicates rational advances towards orthogonality.     

EPR Studies of the Binding Properties,Guest Dynamics,and Inner‐Space Dimensions of a Water‐Soluble Resorcinarene Capsule

Nitroxide free radicals have been used to study the inner space of one of Rebek’s water‐soluble capsules. EPR and ¹H NMR spectroscopy, ESI‐MS, and DFT calculations showed a preference for the formation of 1:2 complexes. EPR titrations allowed us to determine binding constants (K_a) in the order of 10⁷ M ^?2. EPR spectral‐shape analysis provided information on the guest rotational dynamics within the capsule. The interplay between optimum hydrogen bonding upon capsule formation and steric strain for guest accommodation highlights some degree of flexibility for guest inclusion, particularly at the center of the capsule where the hydrogen bond seam can be barely distorted or slightly disturbed.     

Structure and Dynamics of Oligonucleotides in the Gas Phase

By combining ion‐mobility mass spectrometry experiments with sub‐millisecond classical and ab initio molecular dynamics we fully characterized, for the first time, the dynamic ensemble of a model nucleic acid in the gas phase under electrospray ionization conditions. The studied oligonucleotide unfolds upon vaporization, loses memory of the solution structure, and explores true gas‐phase conformational space. Contrary to our original expectations, the oligonucleotide shows very rich dynamics in three different timescales (multi‐picosecond, nanosecond, and sub‐millisecond). The shorter timescale dynamics has a quantum mechanical nature and leads to changes in the covalent structure, whereas the other two are of classical origin. Overall, this study suggests that a re‐evaluation on our view of the physics of nucleic acids upon vaporization is needed.     

Diketopyrrolopyrrole‐Porphyrin Conjugates with High Two‐Photon Absorption and Singlet Oxygen Generation for Two‐Photon Photodynamic Therapy

Two‐photon photodynamic therapy is a promising therapeutic method which requires the development of sensitizers with efficient two‐photon absorption and singlet‐oxygen generation. Reported here are two new diketopyrrolopyrrole‐porphyrin conjugates as robust two‐photon absorbing dyes with high two‐photon absorption cross‐sections within the therapeutic window. Furthermore, for the first time the singlet‐oxygen generation efficiency of diketopyrrolopyrrole‐containing systems is investigated. A preliminary study on cell culture showed efficient two‐photon induced phototoxicity.     

Fine Tuning of β‐Peptide Foldamers: a Single Atom Replacement Holds Back the Switch from an 8‐Helix to a 12‐Helix

Cyclic homologated amino acids are important building blocks for the construction of helical foldamers. N‐aminoazetidine‐2‐carboxylic acid (AAzC), an aza analogue of trans‐2‐aminocyclobutanecarboxylic acid (tACBC), displays a strong hydrazino turn conformational feature, which is proposed to act as an 8‐helix primer. tACBC oligomers bearing a single N‐terminal AAzC residue were studied to evaluate the ability of AAzC to induce and support an 8‐helix along the oligopeptide length. While tACBC homooligomers assume a dominant 12‐helix conformation, the aza‐primed oligomers preferentially adopt a stabilized 8‐helix conformation for an oligomer length up to 6 residues. The (formal) single‐atom exchange at the N terminus of a tACBC oligomer thus contributes to the sustainability of the 8‐helix, which resists the switch to a 12‐helix. This effect illustrates atomic‐level programmable design for fine tuning of peptide foldamer architectures.