Acyclic Cucurbit[n]uril Receptors Function as Solid State Sequestrants for Organic Micropollutants.

The accumulation of organic micropollutants (OMP) in aquatic systems is a major societal problem that can be addressed by approaches including nanofiltration, flocculation, reverse osmosis and adsorptive methods using insoluble materials (e.g. activated carbon, MOFs, nanocomposites). More recently, polymeric versions of supramolecular hosts (e.g. cyclodextrins, calixarenes, pillararenes) have been investigated as OMP sequestrants. Herein, we report our study of the use of water insoluble dimethylcatechol walled acyclic cucurbit[n]uril (CB[n]) hosts as solid state sequestrants for a panel of five OMPs. A series of hosts (H1-H4) were synthesized by reaction of glycoluril oligomer (monomer-tetramer) with 3,6-dimethylcatechol and fully characterized by spectroscopic means and x-ray crystallography. The solid hosts sequester OMPs from water with removal efficiencies exceeding 90 % in some cases. The removal efficiencies of the new hosts parallel the known molecular recognition properties of analogous water soluble acyclic CB[n]. OMP uptake by solid host occurs rapidly (≈120 seconds). Head-to-head comparison with CB[6] in batch-mode separation and DARCO activated carbon in flow-through separation mode show that tetramer derived host (H4) performs very well under identical conditions. The work establishes insoluble acyclic CB[n]-type receptors as a promising new platform for OMP sequestration.

An easily accessible, lower rim substituted calix[4]arene selectively binds N,N-dimethyllysine.

Post-translational modifications (PTMs) are critical controllers of protein functions. One set of important PTMs are N-methylated side chains of lysine and arginine, which exist in several functionally distinct forms. Multiple groups have demonstrated the selective binding of the most hydrophobic family member, trimethyllysine (Kme3), using various macrocyclic hosts, but the selective binding of lower methylation states remains challenging. Herein we report that the installation of a sulfonate ester on the lower rim phenol of p-sulfonatocalix[4]arene efficiently generates a potent, N,N-dimethyllysine (Kme2)-selective host in one step from commercially available starting materials. We characterize its binding behaviors in solution, and examine the relationship between its unusual conformational dynamics and its guest-binding properties.

Using reversible non-covalent and covalent bonds to create assemblies and equilibrating molecular networks that survive 5 molar urea.

The limits of self-assembly and host-guest chemistry in water solutions containing competitive solutes are largely unexplored. We report here a new family of self-assembling systems that are stitched together at two levels by reversible hydrazone bonds and by non-covalent self-assembly in strongly denaturing conditions. Three different hydrazides of various charge and hydrophobicity are combined with an aldehyde-containing calixarene, and each system spontaneously forms AB hydrazones that subsequently self-assemble into four-component (AB)2 structures in water. The assemblies display varying responses to added NaCl and/or urea. The most robust assembly survives completely intact in solution up to 5 M urea. We also combine the aldehyde calixarene with two different hydrazides in the same tube to create complex, competitive dynamic libraries. We report experiments in which the composition of the dynamic equilibrating library is under the control of self-assembly, allowing the systems to choose the components that form the most stable assemblies under a variety of competitive solutions conditions. These dynamic networks of equilibrating molecules maintain remarkably similar equilibrium positions under widely varying concentrations of urea and NaCl.

Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.

Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.

Attraction by repulsion: compounds with like charges undergo self-assembly in water that improves in high salt and persists in real biological fluids.

We report a family of highly anionic calixarenes that form discrete homo-dimeric assemblies in pure water, that get stronger in high salt solutions, and that remain assembled in complex, denaturing solutions like real urine. The results reveal the potential of like-charged subunits for self-assembly in high-salt solutions and biological fluids.

A highly selective chemodosimeter for fast detection and intracellular imaging of Hg2+ ions based on a dithiocarbamate-isothiocyanate conversion in aqueous ethanol.

A new naphthalene diimide-dithiocarbamate based fluorescence probe was synthesized and its fluorogenic behavior towards various metal ions was studied. Upon addition of various metal ions, the probe afforded an irreversible change only with Hg(2+) ions in aqueous-ethanol media (4 : 1 v/v) with a fourfold enhancement of the fluorescence (Φ = 0.03 → 0.11) along with a distinct 43 nm blue shift of the emission maxima. The mechanism of the chemodosimetric behavior of the probe has been attributed to a Hg(2+) induced transformation of a weakly fluorescent dithiocarbamate to a highly fluorescent isothiocyanate which has been characterized by a number of spectroscopic techniques and a crystal structure. Intracellular detection of Hg(2+) ions was achieved using the probe.