Enhancing antibacterial efficacy through macrocyclic host complexation of fluoroquinolone antibiotics for overcoming resistance.

The use of supramolecular assemblies in pharmaceuticals has garnered significant interest. Recent studies have shown that the activities of antibacterial agents can be enhanced through complexation with cyclic oligomers and metal ions. Notably, these complexes sometimes possess greater therapeutic properties than the parent drugs. To develop microbiologically potent supramolecular drugs, the complexation of macrocyclic hosts with fluoroquinolone (FQ) antibiotics was investigated. FQs are a successful family of antibiotics that target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, leading to bacterial cell death through the inhibition of DNA synthesis. However, antibiotic resistance resulting from the repeated use of FQs over time has limited their effectiveness against resistant pathogens. To overcome this issue, the encapsulation of FQs in polyphenolic macrocycles was investigated. This study highlights resorcinarene, a polyphenolic host with antibacterial properties, and its ability to chemically interact with FQs. The inclusion complexation process was analyzed using NMR and FTIR techniques. The binding constants determined by 1H-NMR titration revealed that levofloxacin forms more stable complexes with resorcinarene than with ß-cyclodextrin, which aligned with MD simulations. Assessment of the geometric characteristics of the inclusion complexes using 2D NMR analysis confirmed that different moieties of various FQs can fit into a single host cavity and improve activity against gram-negative bacteria. Overall, these findings suggest that encapsulation in polyphenolic macrocycles is a promising strategy for utilizing FQs against antibiotic-resistant bacteria.

Dynamic macromolecular material design: the versatility of cucurbituril over cyclodextrin in host-guest chemistry.

The keto-enol tautomerism of avobenzone (AVO) is pivotal to its photostability, influenced by microenvironmental factors, such as, the type of solvent and complexation with macrocyclic compounds. This study explores the effect of host-guest complexation on AVO photostabilization, employing cucurbit[7]uril (CB[7]) and ß-cyclodextrin (ß-CD) to form inclusion complexes. CB[7] exhibits a higher affinity to the keto form of AVO, a UVC radiation absorber. The complexed keto form facilitates the regeneration of the enol form, reducing skin permeation. Spectroscopic and thermal analyses confirm 1 : 1 AVO-CB[7] and AVO-ß-CD complex formation. Computational and MD simulations show that host-guest complex is favored over isolated AVO and ß-CD or CB[7] molecules by 95-125 kJ mol-1, depending on the presence of implicit solvent. Both macrocycles enhance AVO photostabilization in aqueous environments, with CB[7] displaying greater selectivity for the keto form, while ß-CD shows ethanol concentration-dependent binding.

Novel keto-enol tautomerism in 1,3,5-trihydroxybenzene systems.

We report a new synthesis of the water-soluble compound 1,3,5-trihydroxy-2,4,6-trimethylsulfonic acid (1), which exists in two tautomeric forms (60 : 40::enol%:keto%) and can be used as a proton conductor. Quantum chemical calculations show the importance of intramolecular hydrogen bonding and the presence of implicit MeOH solvent on the relative stabilities of the tautomers. 1 complexes with lanthanides through its sulfonato groups and forms a layered cage-like structure with one intramolecular and two intermolecular hydrogen bonds.

Conversion of Pregabalin to 4-Isobutylpyrrolidone-2.

Solid-state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica, Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4-isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation was implemented to further our understanding of the factors affecting the conversion process.