Spotlight on Mechanosterics: A Bulky Macrocycle Promotes Functional Group Reactivity in a [2]Rotaxane.

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Chemical Engineering

Background:

• Macrocycles in mechanically interlocked molecules (MIMs) often sterically hinder adjacent functional groups, reducing their reactivity.
• Understanding how molecular architecture influences chemical reactivity is crucial for designing advanced molecular systems.

Purpose of the Study:

• To investigate the effect of a bulky macrocycle in a [2]rotaxane on the reactivity of an adjacent functional group (Fmoc-derived stopper).
• To elucidate the structural and electronic factors responsible for any observed changes in reactivity.

Main Methods:

• Synthesis and characterization of a [2]rotaxane and a non-interlocked control.
• Kinetic studies to measure the rate of Fmoc deprotection under basic conditions.
• Nuclear Magnetic Resonance (NMR) spectroscopy, Single-Crystal X-ray Diffraction (SC-XRD), and Density Functional Theory (DFT) calculations to analyze molecular structure and interactions.

Main Results:

• The [2]rotaxane exhibited a 36-fold acceleration in Fmoc deprotection compared to the non-interlocked control.
• Structural analysis revealed preorganization of the macrocycle and stopper, exposing the reactive site.
• DFT and spectroscopic studies identified specific CH-π interactions and hydrogen bonding stabilizing the reactive conformation.

Conclusions:

• Molecular entanglement in [2]rotaxanes can promote, rather than hinder, the reactivity of functional groups through precise spatial control.
• The observed acceleration is attributed to macrocycle-induced preorganization and specific non-covalent interactions.
• This work provides a new paradigm for designing molecular machines with enhanced functional components.