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Misregulation of transmembrane ion transport in biological systems has been linked to a variety of diseases. As a result, supramolecular chemists have been trying to develop small molecules that facilitate the transmembrane transport of several ionic species. However, ion transport by small molecules is a passive process and needs to be overall charge neutral (i.e., when an ion is transported across a membrane, another ion needs to be transported as well to avoid charge separation). Ion pair receptors could therefore have great potential as transmembrane ion transporters because they can facilitate transport of an overall neutral species. Furthermore, ditopic ion pair receptors also have the potential to transport biologically important zwitterionic species, such as amino acids. In this manuscript, we report the synthesis of a series of ditopic receptors based on squaramides as the anion binding unit and 18-crown-6 as the cation binding unit. UV-vis and NMR titrations revealed that these compounds can bind a variety of chloride salts, especially KCl. Furthermore, liquid–liquid extractions and transport experiments using bulk liquid membranes and liposomes indicate that these ditopic receptors are capable of transporting chloride salts and hydrophilic amino acids. In fact, compound 5 was even able to facilitate the transport of amino acids with charged side chains at physiological pH (arginine and glutamate), making it the first example of a small molecule that can transport these highly polar and charge-dense species. These findings open up the possibility of using these receptors in a wide range of biological applications. 

The North American Supramolecular Chemistry (NASC) meetings were established 3 years ago to strengthen the supramolecular chemistry community in North America and to provide a platform for researchers at any stage of their career to present their work and allow network opportunities. NASC 2024 was the third edition of this annual conference and once again showcased the breadth of the field with talks on metal-organic cages and frameworks, anion binding, supramolecular chemistry in space, and many other topics. In this proceedings article, a selection of speakers provides their impression of the NASC 2024 meeting and the field of supramolecular chemistry. 

Anions play an important role in our life, from storing our genetic code on the polyanion DNA, to being the active ingredient in agricultural fertilizers and other industrial processes. Consequently, chemists have been designing systems that can sense anionic species through a variety of methods, such as unimolecular chromophores or sensor arrays. Nonetheless, most existing sensing approaches still have some drawbacks, particularly related to obtaining adequate selectivity and achieving sensing of anions in aqueous environments. In this manuscript, we report a liquid-liquid extraction (LLE)-based sensing approach that allows the conversion of non-selective optical anion sensors that only work in organic media, into selective sensing systems that allow detection of anions in water. We tested this approach on deprotonation-based anion sensors (alizarin, naphthol AS, 4-nitrophenol, BI-Lawsone, and chromophore 1) and hydrogen bonding-based anion sensors (1,2-diaminoanthraquinone and 4-nitro-1,2-phenylenediamine). In general, the deprotonation-based sensors could be converted from a non-selective sensor for basic anions (NCO¯, H2PO4¯, AcO¯ and F¯) to a selective sensing system for NCO¯ with the aid of carefully chosen tetraalkylammonium salts as extracting agents. On the other hand, the hydrogen-bonding based sensors could be converted to a selective sensing system for the hydrophobic anion ClO4¯ using similar tetraalkylammonium salts. 

Abstract The World Health Organization has described the antimicrobial resistance crisis as one of the top ten global public health threats. New antimicrobial agents that can fight infections caused by antimicrobial resistant pathogens are therefore needed. A potential strategy is the development of small molecules that can selectively interact with bacterial membranes (or membranes of other microbial pathogens), and thereby rapidly kill the bacteria. Here, we report the structure‐activity relationship within a group of 22 compounds that were designed to bind the bacterial lipid phosphatidylethanolamine (PE). Liposome‐based studies reveal that the lipophilicity of the compounds has the strongest effect on both the affinity and selectivity for PE. The best results were obtained for compounds with logP≈3.75, which showed a 5x–7x selectivity for bacterial PE lipids over human PC (phosphatidylcholine) lipids. Furthermore, these compounds also showed potent antibacterial activity against the Gram‐positive bacteriumB. cereus, with minimum inhibitory concentrations (MICs) below 10 μM, a concentration where they showed minimal hemolytic activity against human red blood cells. These results not only show the possibility of PE‐binding small molecules to function as antibiotics, but also provide guidelines for the development of compounds targeting other types of biologically relevant membrane lipids. 

Early-career scientists need opportunities to present their research and to network. Within the supramolecular chemistry community, local conferences that provide such opportunities have arisen over the last few decades. However, a suitable conference in North America was still missing. In 2022, we therefore organized the first North American Supramolecular Chemistry (NASC) meeting to bring together supramolecular chemists from across the continent and to provide career building opportunities for PhD students and postdocs. For this Conference Proceeding, we asked some of the invited speakers, as well as the winners of the best talk prizes, to provide their opinion of the meeting and their vision on the future of supramolecular chemistry in North America. 

An increasing number of people are infected with antibiotic-resistant bacteria each year, sometimes with fatal consequences. In this manuscript, we report a novel urea-functionalized crown ether that can bind to the bacterial lipid phosphatidylethanolamine (PE), facilitate PE flip-flop and displays antibacterial activity against the Gram-positive bacterium Bacillus cereus with a minimum inhibitory concentration comparable to that of the known PE-targeting lantibiotic duramycin.