Enhanced Circularly Polarized Luminescence of Urea-Bridged Dimers of Axially Chiral BODIPY-Carbohydrate Hybrids.

Herein, we report the synthesis of novel dimeric urea-bridged BODIPY-carbohydrate conjugates, which display circularly polarized luminescence (CPL). The dimers are composed of diastereomerically pure, axially chiral (P or M) BODIPY monomers containing a pendant glucose (d- or l-) unit. The latter was intended to add chirality, biocompatibility, and enhanced water solubility and facilitate the chromatographic resolution of the intermediate atropisomers.

Opposed Aromatic Surfaces Behave as Independent Binding Sites for Carbohydrate Stacking: Analysis of Sandwich-like CH/π/CH Complexes.

CH/π bonds are versatile elements for the construction of complex molecular architectures, thus playing key roles in many biomolecular recognition processes. Although seldom acknowledged, aromatic units are inherently bivalent and can participate in CH/π bonds through either face simultaneously, leading to the formation of stacking complexes. This sandwich-like arrangement is by far the most common in natural complexes and could potentially lead to negative cooperativity due to unfavorable polarization or electrostatic effects, especially when polarized CH fragments are involved.

Illuminating a Solvent-Dependent Hierarchy for Aromatic CH/π Complexes with Dynamic Covalent Glyco-Balances.

CH/π interactions are prevalent among aromatic complexes and represent invaluable tools for stabilizing well-defined molecular architectures. Their energy contributions are exceptionally sensitive to various structural and environmental factors, resulting in a context-dependent nature that has led to conflicting findings in the scientific literature. Consequently, a universally accepted hierarchy for aromatic CH/π interactions has remained elusive.

Binding-driven reactivity attenuation enables NMR identification of selective drug candidates for nucleic acid targets.

NMR methods, and in particular ligand-based approaches, are among the most robust and reliable alternatives for binding detection and consequently, they have become highly popular in the context of hit identification and drug discovery. However, when dealing with DNA/RNA targets, these techniques face limitations that have precluded widespread application in medicinal chemistry. In order to expand the arsenal of spectroscopic tools for binding detection and to overcome the existing difficulties, herein we explore the scope and limitations of a strategy that makes use of a binding indicator previously unexploited by NMR: the perturbation of the ligand reactivity caused by complex formation.

Aromatic Interactions in Glycochemistry: From Molecular Recognition to Catalysis.

Aromatic platforms are ubiquitous recognition motifs occurring in protein carbohydrate- binding domains (CBDs), RNA receptors and enzymes. They stabilize the glycoside/ receptor complexes by participating in stacking CH/π interactions with either the α- or β- face of the corresponding pyranose units. In addition, the role played by aromatic units in the stabilization of glycoside cationic transition states has started being recognized in recent years.

De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot.

Invited for the cover of this issue are Andrés G. Santana, Carlos González, Juan Luis Asensio and co-workers at Instituto de Química Orgánica General, Instituto de Química-Física Rocasolano and Universidad de La Rioja. The image depicts drug selectivity using a metaphor of an arrow hitting a target.

De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot.

Targeting the interface between DNA quadruplex and duplex regions by small molecules holds significant promise in both therapeutics and nanotechnology. Herein, a new pharmacophore is reported, which selectively binds with high affinity to quadruplex-duplex junctions, while presenting a poorer affinity for G-quadruplex or duplex DNA alone. Ligands complying with the reported pharmacophore exhibit a significant affinity and selectivity for quadruplex-duplex junctions, including the one observed in the HIV-1 LTR-III sequence.

Single-Step Glycosylations with C-Labelled Sulfoxide Donors: A Low-Temperature NMR Cartography of the Distinguishing Mechanistic Intermediates.

Glycosyl sulfoxides have gained recognition in the total synthesis of complex oligosaccharides and as model substrates for dissecting the mechanisms involved. Reactions of these donors are usually performed under pre-activation conditions, but an experimentally more convenient single-step protocol has also been reported, whereby activation is performed in the presence of the acceptor alcohol; yet, the nature and prevalence of the reaction intermediates formed in this more complex scenario have comparatively received minimal attention. Herein, a systematic NMR-based study employing both C-labelled and unlabelled glycosyl sulfoxide donors for the detection and monitoring of marginally populated intermediates is reported.

Dissecting the Essential Role of Anomeric β-Triflates in Glycosylation Reactions.

Glycosylations promoted by triflate-generating reagents are widespread synthetic methods for the construction of glycosidic scaffolds and glycoconjugates of biological and chemical interest. These processes are thought to proceed with the participation of a plethora of activated high energy intermediates such as the α- and β-glycosyl triflates, or even increasingly unstable glycosyl oxocarbenium-like species, among which only α-glycosyl triflates have been well characterized under representative reaction conditions. Interestingly, the remaining less accessible intermediates, yet to be experimentally described, seem to be particularly relevant in α-selective processes, involving weak acceptors.

N-BODIPYs Come into Play: Smart Dyes for Photonic Materials.

N-BODIPYs (diaminoboron dipyrromethenes) are unveiled as a new family of BODIPY dyes with huge technological potential. Synthetic access to these systems has been gained through a judicious design focused on stabilizing the involved diaminoboron chelate. Once stabilized, the obtained N-BODIPYs retain the effective photophysical behavior exhibited by other boron-substituted BODIPYs, such as O-BODIPYs.