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Tridecaptins comprise a class of linear cationic lipopeptides with an N-terminal fatty acyl moiety. These 13-mer antimicrobial peptides consist of a combination of d- and l-amino acids, conferring increased proteolytic stability. Intriguingly, they are biosynthesized by non-ribosomal peptide synthetases in the same bacterial species that also produce the cyclic polymyxins displaying similar fatty acid tails. Previously, the des-acyl analog of TriA 1 (termed H-TriA 1 ) was found to possess very weak antibacterial activity, albeit it potentiated the effect of several antibiotics. In the present study, two series of des-acyl tridecaptins were explored with the aim of improving the direct antibacterial effect. At the same time, overall physico-chemical properties were modulated by amino acid substitution(s) to diminish the risk of undesired levels of hemolysis and to avoid an impairment of mammalian cell viability, since these properties are typically associated with highly hydrophobic cationic peptides. Microbiology and biophysics tools were used to determine bacterial uptake, while circular dichroism and isothermal calorimetry were used to probe the mode of action. Several analogs had improved antibacterial activity (as compared to that of H-TriA 1 ) against Enterobacteriaceae. Optimization enabled identification of the lead compound 29 that showed a good ADMET profile as well as in vivo efficacy in a variety of mouse models of infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram-negative bacteria. Sil proteins also bind Cu(I) but with reported weaker affinity, therefore leading to the designation of a specific detoxification system for Ag(I). Using isothermal titration calorimetry, we show that binding of both ions is not only tighter than previously thought but of very similar affinities. We investigated the structural origins of ion binding using molecular dynamics and QM/MM simulations underpinned by structural and biophysical experiments. The results of this analysis showed that the binding site adapts to accommodate either ion, with key interactions with the solvent in the case of Cu(I). The implications of this are that Gram-negative bacteria do not appear to have evolved a specific Ag(I) efflux system but take advantage of the existing Cu(I) detoxification system. Therefore, there are consequences for how we define a particular metal resistance mechanism and understand its evolution in the environment., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cyanine dyes are known to form H - and J -aggregates in aqueous solutions. Here we show that the cyanine dye, S0271, assembles in water into vortex induced chiral J -aggregates. The chirality of the J -aggregates depends on the directionality of the vortex. This study utilised both conventional benchtop CD spectropolarimeters and Mueller matrix polarimetry. It was found that J -aggregates have real chirality alongside linear dichroism and linear and circular birefringence. We identify the factors that are key to the formation of metastable chiral J -aggregates and propose a mechanism for their assembly.

Designing the architecture of L-lysine-based polymeric structures is a highly challenging task that requires careful control of the amino acid reactive groups. Conventional processes to obtain branched polylysine need several steps and the addition of specific catalysts. In the present work, to gain a better understanding and control of the formation of L-lysine-based polymers, we have investigated the correlation between the protonation state of L-lysine and the corresponding hydrothermally grown structures. The samples have been characterized by combining optical spectroscopies, such as UV-Vis, fluorescence, and synchrotron radiation circular dichroism with structural analysis by Nuclear Magnetic Resonance, Fourier Transform Infrared spectroscopy, and dynamic light scattering. We have observed that aqueous precursor solutions with alkaline pHs promote the formation of branched structures. In contrast, high pHs favour the reactivity of the ε-amino groups leading to linear structures, as shown by circular dichroism analyses. On the other hand, acidic conditions trigger the branching of the amino acid. Interestingly, the polymeric forms of L-lysine emit in the blue because the increasing number of intermolecular hydrogen bonds promote the intermolecular charge transfer responsible for the emission. Understanding the correlation between the L-lysine charged states and the polymeric structures that could form controlling the protonation-deprotonation states of the amino acid opens the route to a refined design of polypeptide systems based on L-lysine., (© 2022. The Author(s).)

The first example of uniformly chiral thin films of silicon phthalocyanines (SiPcs) are reported. The local domains of the films are mapped using circular dichroism (CD) imaging (CD i ) technique available at the Diamond B23 beamline. The CD i allowed us to increase the spatial resolution up to 525× when compared with benchtop spectrometers. The results indicate formation on-surface of chiral and stable supramolecular assemblies with homogenous distribution. Chemical functionalization and solvent choice for deposition allow controllable chiroptical properties to be obtained. The method and technique reported in this work could be applied to prepare and characterize a wide variety of chiral thin films.

We report herein the first all-donor aromatic [2]catenane formed through dynamic combinatorial chemistry, using single component libraries. The building block is a benzo[1,2- b :4,5- b ']dithiophene derivative, a π-donor molecule, with cysteine appendages that allow for disulfide exchange. The hydrophobic effect plays an essential role in the formation of the all-donor [2]catenane. The design of the building block allows the formation of a quasi-fused pentacyclic core, which enhances the stacking interactions between the cores. The [2]catenane has chiro-optical and fluorescent properties, being also the first known DCC-disulphide-based interlocked molecule to be fluorescent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Structurally Divergent Reactions on Racemic Mixtures are atypical processes in Nature. The few examples reported in the literature take place in organic solvents and are driven by the reagents' interaction with bulky chiral catalysts. Herein, we describe a dynamic combinatorial approach to generate structural divergence from racemic building blocks. The divergence is due to a stereospecific electron-donor - electron-acceptor interaction of diastereomeric macrocycles, leading to structurally distinct pseudorotaxanes. The equilibrated dynamic combinatorial library contains, amongst various macrocycles, two different types of [2]catenanes that are non-isomeric. The formation of these [2]catenanes is due to a spontaneous stereo and structurally divergent assembly of the building blocks.

A novel approach to axially induce chirality on silicon phthalocyanines via a microwave-assisted route is reported. CD analysis provides spectroscopic evidence that chirality is transferred onto both Soret and Q-bands of the phthalocyanine core. A chiral naphthalenediimide ligand was found to induce the largest Cotton effect on the macrocycle absorptions.