The design and optimization of fluorescent molecules has driven the ability to interrogate complex biological events in real time. Notably, most advances in bioimaging fluorophores are based on optimization of core structures that have been known for over a century. Recently, new synthetic methods have resulted in an explosion of nonplanar conjugated macrocyclic molecules with unique optical properties yet to be harnessed in a biological context. Herein we report the synthesis of the first aqueous-soluble carbon nanohoop (i.e., a macrocyclic slice of a carbon nanotube prepared via organic synthesis) and demonstrate its bioimaging capabilities in live cells. Moreover, we illustrate that these scaffolds can be easily modified by well-established “click” chemistry to enable targeted live cell imaging. This work establishes the nanohoops as an exciting new class of macrocyclic fluorophores poised for further development as novel bioimaging tools.

Upon exposure to Scholl reaction conditions, cycloparaphenylenes undergo facile strain-relieving rearrangements and ring-openings.

This tutorial review covers recently developed technologies employed for chemical synthesis, derivatization and analysis of lipids.

The unique optoelectronic properties and smooth, rigid pores of macrocycles with radially oriented p systems render them fascinating candidates for the design of novel mechanically interlocked molecules with new properties.T wo high-yielding strategies are used to prepare nanohoop [2]rotaxanes,which owing to the p-rich macrocycle are highly emissive. Then, metal coordination, an intrinsic property afforded by the resulting mechanical bond, can lead to molecular shuttling as well as modulate the observed fluorescence in both organic and aqueous conditions.Inspired by these findings,aself-immolative [2]rotaxane was then designed that self-destructs in the presence of an analyte,e liciting as trong fluorescent turn-on response,s erving as proof-of-concept for an ew type of molecular sensing material. More broadly,this work highlights the conceptual advantages of combining compact p-rich macrocyclic frameworks with mechanical bonds formed via active-template syntheses.

Constrained macrocyclic scaffolds are recognized as challenging synthetic motifs with few general macrocyclization methods capable of accessing these types of systems. Although palladium catalyzed oxidative homocoupling of aryl boronic acids and esters to biphenyls has been recognized as a common byproduct in Suzuki-Miyaura cross-couplings for decades, this reactivity has not been leveraged for the synthesis of challenging molecules. Here we report an oxidative boronic ester homocoupling reaction as a mild method for the synthesis of strained and conformationally restricted macrocycles. Higher yields and better efficiencies are observed for intramolecular diboronic ester homocouplings when directly compared to the analogous intramolecular Suzuki-Miyaura cross-couplings or reductive Yamamoto homocouplings. Substrates included strained polyphenylene macrocycles, strained cycloalkynes, and a key macrocyclic intermediate toward the synthesis of acerogenin A. Notably, this oxidative homocoupling reaction is performed at room temperature, open to atmosphere, and without the need to rigorously exclude water, thus representing an operationally simple alternative to traditional cross-coupling macrocyclizations. The mechanism of the reaction was investigated indicating that 1-5 nm palladium nanoparticles may serve as the active catalyst.

Strategies to visualize cellular membranes with light microscopy are restricted by the diffraction limit of light, which far exceeds the dimensions of lipid bilayers. Here, we describe a method for super-resolution imaging of metabolically labeled phospholipids within cellular membranes. Guided by the principles of expansion microscopy, we develop an all-small molecule approach that enables direct chemical anchoring of bioorthogonally labeled phospholipids into a hydrogel network and is capable of super-resolution imaging of cellular membranes. We apply this method, termed lipid expansion microscopy (LExM), to visualize organelle membranes with precision, including a unique class of membrane-bound structures known as nuclear invaginations. Compatible with standard confocal microscopes, LExM will be widely applicable for super-resolution imaging of phospholipids and cellular membranes in numerous physiological contexts.

Abstract:The design and optimization of fluorescent molecules has driven the ability to interrogate complex biological events in real time. Notably, most advances in bioimaging fluorophores are based on optimization of core structures that have been known for over a century. Recently, new synthetic methods have resulted in an explosion of non-planar conjugated macrocyclic molecules with unique optical properties yet to be harnessed in a biological context. Herein we report the synthesis of the first aqueous-soluble carbon nanohoop (i.e. a macrocyclic slice of a carbon nanotube prepared via organic synthesis) and demonstrate its bioimaging capabilities in live cells. This work establishes the nanohoops as an exciting new class of macrocyclic fluorophores poised for further development as novel bioimaging tools.

No abstract