Reactivity and selectivity modulation within a molecular assembly: recent examples from photochemistry

In recent years, photochemical reactions have emerged as powerful transformations which significantly expand the repertoire of organic synthesis. However, a certain lack of selectivity can hamper their application and limit their scope. In this context, a major research effort continues to focus on an improved control over stereo- and chemoselectivity that can be achieved in molecular assemblies between photosubstrates and an appropriate host molecule. In this tutorial review, some recent, representative examples of photochemical reactions have been collected whose unique outcome is dictated by the formation of a molecular assembly driven by non-covalent weak interactions. Graphical Abstract

A Fluorescent Detection for Paraquat Based on β-CDs-Enhanced Fluorescent Gold Nanoclusters

In this report, a fluorescent sensing method for paraquat based on gold nanoclusters (AuNCs) is proposed. It was found that paraquat could quench both glutathione-capped AuNCs (GSH-AuNCs) and β-cyclodextrin-modified GSH-AuNCs (GSH/β-CDs-AuNCs). The modification of β-CDs on the surface of GSH-AuNCs obviously enhanced the fluorescence intensity of GSH-AuNCs and improved the sensitivity of paraquat sensing more than 4-fold. This sensibilization was ascribed to the obvious fluorescence intensity enhancement of GSH-AuNCs by β-CDs and the “host–guest” interaction between paraquat and β-CDs. The fluorescence quenching was mainly due to the photoinduced energy transfer (PET) between GSH/β-CDs-AuNCs and paraquat. With the optimized β-CDs modification of the GSH-AuNC surfaces and under buffer conditions, the fluorescent detection for paraquat demonstrated a linear response in the range of 5.0–350 ng/mL with a detection limit of 1.2 ng/mL. The fluorescent method also showed high selectivity toward common pesticides. The interference from metal ions could be easily masked by ethylene diamine tetraacetic acid (EDTA). This method was applied to the measurement of paraquat-spiked water samples and good recoveries (93.6–103.8%) were obtained. The above results indicate that host molecule modification of fluorescent metal NC surfaces has high potential in the development of robust fluorescent sensors.

Crystal structure of a methanol solvate of a macrocycle bearing two flexible side-arms

Di-tert-butyl N,N′-{[13,15,28,30,31,33-hexaethyl-3,10,18,25,32,34-hexaazapentacyclo[25.3.1.15,8.112,16.120,23]tetratriaconta-1(31),3,5,7,9,12(33),13,15,18,20,22,24,27,29-tetradecaene-14,29-diyl]bis(methylene)}dicarbamate methanol disolvate, C52H72N8O4·2CH3OH, was found to crystallize in the space group P21/c with one half of the macrocycle (host) and one molecule of solvent (guest) in the asymmetric unit of the cell, i.e. the host molecule is located on a crystallographic symmetry center. Within the 1:2 host–guest complex, the solvent molecules are accommodated in the host cavity and held in their positions by O—H...N and N—H...O bonds, thus forming ring synthons of graph set R 2 2(7). The connection of the 1:2 host-guest complexes is accomplished by C—H...O, C—H...N and C—H...π interactions, which create a three-dimensional supramolecular network.

Macrocyclic host molecules with aromatic building blocks: state of art and progress

Macrocyclic host molecule plays the central role in host-guest chemistry and supramolecular chemistry. Highly structural symmetry of macrocyclic host molecules can meet people's pursuit of aesthetics in molecular design, and...

Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms.

: Drugs have to overcome numerous barriers to reach their desired therapeutic targets. In several cases drugs, especially the highly lipophilic molecules, suffer from low solubility and bioavailability and therefore their desired targeting is hampered. In addition, undesired metabolic products might be produced or off-targets could be recognized. Along these lines, nanopharmacology has provided new technological platforms, to overcome these boundaries. Specifically, numerous vehicle platforms such as cyclodextrins and calixarenes have been widely utilized to host lipophilic drugs such as antagonists of the angiotensin II AT1 receptor (AT1R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves the therapeutic index. In this minireview we report on the formulations of Silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin’s and candesartan’s stability, respectively. Moreover we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.

Selective Binding of a Lower Lysine Methylation State: An N,N-Dimethyllysine Selective Host Molecule and Its Use in Methyl Proteomics

<p>Post-translational modifications (PTMs) are critical controllers of protein functions. One set of important PTMs are <i>N</i>-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 a new calixarene modification – the installation of a sulfonate ester at the lower rim of <i>p</i>-sulfonatocalix[4]arene —efficiently generates a <i>N,N</i>-dimethyllysine (Kme2)-selective host. We characterize its binding behaviors in solution, and demonstrate its effectiveness in a pan-methyllysine enrichment step that enables the observation of hundreds of otherwise unobservable methylation marks in global proteomics experiments.</p><p>The submission includes a manuscript preprint, supporting information, and a tabulation of proteomics data.</p>

Selective Binding of a Lower Lysine Methylation State: An N,N-Dimethyllysine Selective Host Molecule and Its Use in Methyl Proteomics

<p>Post-translational modifications (PTMs) are critical controllers of protein functions. One set of important PTMs are <i>N</i>-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 a new calixarene modification – the installation of a sulfonate ester at the lower rim of <i>p</i>-sulfonatocalix[4]arene —efficiently generates a <i>N,N</i>-dimethyllysine (Kme2)-selective host. We characterize its binding behaviors in solution, and demonstrate its effectiveness in a pan-methyllysine enrichment step that enables the observation of hundreds of otherwise unobservable methylation marks in global proteomics experiments.</p><p>The submission includes a manuscript preprint, supporting information, and a tabulation of proteomics data.</p>

Effect of α-Bisabolol and Its β-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains

Efflux pumps are proteins present in the plasma membrane of bacteria, which transport antibiotics and other compounds into the extracellular medium, conferring resistance. The discovery of natural efflux pump inhibitors is a promising alternative. α-Bisabolol is a sesquiterpene isolated from several plants such as Matricaria chamomilla L. and has important properties such as antibacterial and anti-inflammatory activity. Currently, the formation of inclusion complexes with β-Cyclodextrin has been used for improving the physicochemical characteristics of the host molecule. This study evaluated the effect of α-Bisabolol, in isolation and in complexation with β-Cyclodextrin, as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) was determined. Subsequently, inhibitory activity over the pumps was observed by an MIC reduction for the antibiotics, by using subinhibitory concentrations (MIC/8) in combination with tetracycline and norfloxacin. The MIC of the compounds was ≥1024 μg/mL. α-Bisabolol potentiated the action of tetracycline and reduced the MIC of norfloxacin to a clinically relevant concentration. The complexed substance showed synergism however, the effect of the isolated α-Bisabolol was superior to the complex. These results indicate α-Bisabolol is a potential substance to be used as an efflux pump inhibitor.

Supra-blot: an accurate and reliable assay for detecting target proteins with a synthetic host molecule–enzyme hybrid

A new way to detect target proteins is developed using a high-affinity host–guest interaction for a wide variety of biological samples including bacteria and mammalian cells.