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1. Bisphosphonium Benzene Diimides

   https://doi.org/10.1002/chem.202402791  

   Leake_Gebresilassie, Feven; Ji_Kim, Min; Castellanos, Daniela; Broderick, Conor_H; Ngo, Steven_M; Young, Jr., Victor_G; Cao, Dennis_D (September 2024, Chemistry – A European Journal)

   Abstract The incorporation of cationic groups onto electron‐poor compounds is a viable strategy for achieving potent electron acceptors, as evidenced by reports of air‐stable radical forms of large aromatic diimides such as naphthalene and perylene diimides. These ions have also been observed to exhibit anion–π interaction tendencies of interest in molecular recognition applications. The benefits of phosphonium incorporation, however, have not yet been extended to the smallest benzene diimides. Here, we report that dibrominated pyromellitic diimide and mellophanic diimide both readily undergo substitution reactions with phosphine sources to yield bisphosphonium compounds. In the single crystalline form, these dications display anion‐π interactions and, in the case of mellophanic diimide, the stabilization of a bromide–water H−bonding ring pattern. The reaction of these dications with chemical reductants readily provides the singly and doubly reduced redox states, which were characterized by UV‐vis spectroscopy and found to exhibit intense absorptions extending into the near‐IR region. Taken together, this work demonstrates that phosphonium incorporation onto congested aromatic diimide scaffolds is synthetically viable and produces unusual electron‐poor compounds. 

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2. Evaluation of acyllysine isostere interactions with the aromatic pocket of the AF9 YEATS domain

   https://doi.org/10.1002/pro.4533  

   Travis, Christopher R.; Francis, Denver Y.; Williams, Jr., David C.; Waters, Marcey L. (December 2022, Protein Science)

   Abstract Amide−π interactions, in which an amide interacts with an aromatic group, are ubiquitous in biology, yet remain understudied relative to other noncovalent interactions. Recently, we demonstrated that an electrostatically tunable amide−π interaction is key to recognition of histone acyllysine by the AF9 YEATS domain, a reader protein which has emerged as a therapeutic target due to its dysregulation in cancer. Amide isosteres are commonly employed in drug discovery, often to prevent degradation by proteases, and have proven valuable in achieving selectivity when targeting epigenetic proteins. However, like amide−π interactions, interactions of amide isosteres with aromatic rings have not been thoroughly studied despite widespread use. Herein, we evaluate the recognition of a series of amide isosteres by the AF9 YEATS domain using genetic code expansion to evaluate the amide isostere−π interaction. We show that compared to the amide−π interaction with the native ligand, each isostere exhibits similar electrostatic tunability with an aromatic residue in the binding pocket, demonstrating that the isosteres maintain similar interactions with the aromatic residue. We identify a urea‐containing ligand that binds with enhanced affinity for the AF9 YEATS domain, offering a promising starting point for inhibitor development. Furthermore, we demonstrate that carbamate and urea isosteres of crotonyllysine are resistant to enzymatic removal by SIRT1, a protein that cleaves acyl post‐translational modifications, further indicating the potential of amide isosteres in YEATS domain inhibitor development. These results also provide experimental precedent for interactions of these common drug discovery moieties with aromatic rings that can inform computational methods. 

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3. Tuning surface‐cross‐linking of molecularly imprinted cross‐linked micelles for molecular recognition in water

   https://doi.org/10.1002/jmr.2769  

   Zhang, Shize; Zhao, Yan (November 2018, Journal of Molecular Recognition)

   Abstract Molecular recognition in water is an important challenge in supramolecular chemistry. Surface‐core double cross‐linking of template‐containing surfactant micelles by the click reaction and free radical polymerization yields molecularly imprinted nanoparticles (MINPs) with guest‐complementary binding sites. An important property of MINP‐based receptors is the surface‐cross‐linking between the propargyl groups of the surfactants and a diazide cross‐linker. Decreasing the number of carbons in between the two azides enhanced the binding affinity of the MINPs, possibly by keeping the imprinted binding site more open prior to the guest binding. The depth of the binding pocket can be controlled by the distribution of the hydrophilic/hydrophobic groups of the template and was found to influence the binding in addition to electrostatic interactions between oppositely charged MINPs and guests. Cross‐linkers with an alkoxyamine group enabled two‐stage double surface‐cross‐linking that strengthened the binding constants by an order of magnitude, possibly by expanding the binding pocket of the MINP into the polar region. The binding selectivity among very similar isomeric structures also improved. 

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4. Intramolecularly enhanced molecular tweezers with unusually strong binding for aromatic guests in unfavorable solvents

   https://doi.org/10.1039/C8OB00786A  

   Xing, Xiaoyu; Zhao, Yan (January 2018, Organic & Biomolecular Chemistry)

   Molecular tweezers using aromatic interactions for binding normally work best in polar instead of nonpolar solvents due to the strong solvophobic effect in the binding. Inspired by biological receptors that utilize “delocalized binding interactions” remote from the binding interface to strengthen guest-binding, we constructed molecular tweezers that have a reversed solvent effect. As the direct aromatic binding interactions were weakened by nonpolar solvent, guest-triggered intrahost interactions between two strategically placed carboxylic acids became stronger and contributed to the binding. 

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5. Molecularly Imprinted Polymers (MIPs) in Sensors for Environmental and Biomedical Applications: A Review

   https://doi.org/10.3390/molecules26206233  

   Kadhem, Abbas J.; Gentile, Guillermina J.; Fidalgo de Cortalezzi, Maria M. (October 2021, Molecules)

   Molecular imprinted polymers are custom made materials with specific recognition sites for a target molecule. Their specificity and the variety of materials and physical shapes in which they can be fabricated make them ideal components for sensing platforms. Despite their excellent properties, MIP-based sensors have rarely left the academic laboratory environment. This work presents a comprehensive review of recent reports in the environmental and biomedical fields, with a focus on electrochemical and optical signaling mechanisms. The discussion aims to identify knowledge gaps that hinder the translation of MIP-based technology from research laboratories to commercialization. 

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