Magi Mettry

Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for Lysine Methylation

A dual-mode aggregative host:guest indicator displacement sensing system has been created for the detection of trimethylated peptides and determination of histone demethylase activity. The combination of selective recognition of suitably sized trimethylammonium salts and reversible lipophilic aggregation of the host:guest complex provides a unique quenching mechanism that is not only dependent on affinity for sensitivity but the lipophilicity of the indicator. In addition, aggregation can be controlled by the application of chaotropic anions in the mixture, allowing a second level of discrimination between hard lysine groups and softer trimethyllysines.

Metal-coordinated water-soluble cavitands act as C-H oxidation catalysts.

Cavitands can be smoothly derivatized by CuAAC chemistry to incorporate ligand species at the upper rim. These species can coordinate metal species in a number of different conformations, leading to self-assembly. The metal-coordination confers water solubility on the cavitands, and the iron-bound species are capable of catalytic C-H oxidations of fluorene under mild conditions.

Synthesis, Guest Binding, and Metal Coordination of Functionalized Self-Folding Deep Cavitands

A simple method to introduce donor functions to the upper rim of self-folding benzimidazole-based deep cavitands is described. The upper rim donors allow controlled noncovalent binding of suitably sized guest species via both self-complementary hydrogen bonding and space-filling interactions, and metal-mediated self-folding is possible if bidentate coordinators are incorporated.

Unusual orientation and reactivity of alkyl halides in water-soluble cavitands

Water-soluble deep cavitands with ionic peripheral groups take up hydrophobic guest compounds in D2O. Longer n-halides and α,ω-dihalides C7–C11, are bound and NMR is used to deduce their arrangements within the cavitand. The guests tumble rapidly on the NMR timescale, but unexpectedly, the halogen atoms compete with CH3 groups for the aromatic panels near the bottom of the cavitand. Even a thiol can be found in the depths of the cavitand but not hydroxyl groups: 1,12-dodecanediol folds in the space leaving the ends exposed to solvent. The hydrolysis of bound guests is accelerated when the halides are near the cavitand rim.

Labeled protein recognition at a membrane bilayer interface by embedded synthetic receptors.

Self-folding deep cavitands embedded in a supported lipid bilayer are capable of recognizing suitably labeled proteins at the bilayer interface. The addition of a choline derived binding “handle” to a number of different proteins allows their selective noncovalent recognition, with association constants on the order of 105 M–1. The proteins are displayed at the water:bilayer interface, and a single binding handle allows recognition of the large, charged protein by a small molecule synthetic receptor via complementary shape and charge interactions.

Site-Selective Sensing of Histone Methylation Enzyme Activity via an Arrayed Supramolecular Tandem Assay

Arrayed deep cavitands can be coupled to a fluorescence-based supramolecular tandem assay that allows site-selective in situ monitoring of post-translational modifications catalyzed by the lysine methyltransferase PRDM9 or the lysine demethylase JMJD2E. An arrayed sensor system containing only three cavitand components can detect the specific substrates of enzyme modification, in the presence of other histone peptides in the enzyme assay, enabling investigation of cross-reactivity over multiple methylation sites and interference from nonsubstrate peptides.

Alkane oxidation catalysed by a self-folded multi-iron complex

Abstract A preorganised ligand scaffold is capable of coordinating multiple Fe(II) centres to form an electrophilic CH oxidation catalyst. This catalyst oxidises unactivated hydrocarbons including simple, linear alkanes under mild conditions in good yields with selectivity for the oxidation of secondary CH bonds. Control complexes containing a single metal centre are incapable of oxidising unstrained linear hydrocarbons, indicating that participation of multiple centres aids the CH oxidation of challenging substrates.

Boosting the Heavy Atom Effect by Cavitand Encapsulation: Room Temperature Phosphorescence of Pyrene in the Presence of Oxygen

A deep cavitand is used to encapsulate the aromatic molecule pyrene in its interior while also binding Tl+ ions with its terminal carboxylates. Steady-state and time-resolved spectroscopic experiments, along with quantum yield measurements, quantify the enhancements of intersystem crossing and room temperature phosphorescence due to cavitand encapsulation. These results are compared to those obtained for pyrene contained in sodium dodecyl sulfate micelles, which is the usual system used to generate room temperature phosphorescence. The combination of selective binding and strong Tl+ recognition by the cavitand enhances the intersystem crossing and decreases the phosphorescence radiative lifetime from ∼30 to 0.23 s. The cavitand also decreases the rate of O2 quenching by a factor of 100. Together, these factors can boost the room temperature phosphorescence signal by several orders of magnitude, allowing it to be detected in water without O2 removal. Host:guest recognition provides a route to molecular-scale triplet emitters that can function under ambient conditions.