Solution dependent self-association leads to the production of tuneable hydrogels and spherical aggregates with antimicrobial activity against MRSA and E. coli.

Herein we report 50 structurally related supramolecular selfassociating amphiphilic (SSA) salts and related compounds. These SSAs are shown to act as antimicrobial agents, active against model Gram-positive (methicillin-resistant Staphylococcus aureus) and/or Gram-negative (Escherichia coli) bacteria of clinical interest. Through a combination of solution-state, gasphase, solid-state and in silico measurements, we determine 14 different physicochemical parameters for each of these 50 structurally related compounds. These parameter sets are then used to identify molecular structure-physicochemical propertyantimicrobial activity relationships for our model Gram-negative and Gram-positive bacteria, while simultaneously providing insight towards the elucidation of SSA mode of antimicrobial action.

Herein, we present a series of supramolecular self-associating amphiphilic (SSA) salts and establish the potential for these molecular constructs to act as next-generation solution-state molecular delivery vehicles. We characterise the self-association of these SSAs, both alone and when co-formulated with a variety of drug(like) competitive guest species. Single crystal X-ray diffraction studies enable the observation of hydrogen-bonded self-association events in the solid state, whilst high resolution mass spectrometry confirms the presence of anionic SSA dimers in the gas-phase. These same anionic SSA dimeric species are also identified within a competitive organic solvent environment (DMSO-d6/0.5% H2O). However, extended self-associated aggregates are observed to form under aqueous conditions (H2O/5.0% EtOH) in both the absence and presence of these competitive guest species. Finally, through the completion of these studies, we present a framework to support others in the characterisation of such systems.

Using supramolecular self-associating amphiphiles (SSAs) and antimicrobial/therapeutic agents as combination therapies that lead to increased efficacy against Escherichia coli.

A combination of computational and synthetic phospholipid vesicle/nanodisc assays are used to investigate the mode of action for a class of antimicrobial agents, while a range of DMPK studies establish agent druggability.

Herein we show the potential SSA technology towards the development of synergistic next-generation anticancer treatments.

This review acts as a repository and comparison of cell membrane phospholipid composition data collected from microbial and cancer fields.

As a result of the looming antimicrobial resistance crisis, there is an urgent need for novel antimicrobial treatments. This is particularly true for hard‐to‐treat Gram‐negative bacteria, as many antimicrobial agents are unable to cross the cell membrane to gain access to the cell interior, and thus elicit a therapeutic response. Herein, evidence is provided of the use of anionic supramolecular self‐associating amphiphiles (SSAs) as antimicrobial efficacy enhancers for commonly used antimicrobial agents, to which there is known resistance, against Gram‐negative bacteria. The co‐administration of the SSAs with antimicrobials is shown to sensitize traditionally hard to treat Pseudomonas aeruginosa to both rifampicin and novobiocin, from which structure activity relationships can be elucidated. Quantitative fluorescence microscopy is performed, indicating membrane permeabilization to be the likely mode of action of drug efficacy enhancement by the SSAs. These results offer an alternative strategy in antimicrobial adjuvant design, expanding focus beyond cationic peptides and into the realm of anionic small molecules. Finally, the self‐assembly of the SSAs in the presence of these antimicrobials is investigated through a combination of quantitative NMR, tensiometry, dynamic light scattering, and zeta potential studies, demonstrating the impact of these agents on SSA self‐association events.