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.