‘Frustrated’ hydrogen bond mediated amphiphile self-assembly – a solid state study

Herein, we present the synthesis of ten structurally related ‘frustrated’ amphiphiles, from which were obtained eleven single crystal X-ray structures, allowing observation of the hydrogen bonding modes present in the solid state. We previously reported the synthesis of a novel amphiphilic salt which contains both hydrogen bond donating (HBD) and hydrogen bond accepting (HBA) functionalities. This amphiphilic salt was shown to self-associate in the solution state, aided by the formation of hydrogen bonds. The exact nature of the hydrogen bonding modes involved in this self-association process remains unclear due to the combination of HBD and HBA groups present in the amphiphile structure. This results in a ‘frustrated’ system with access to a variety of possible hydrogen bonding modes

Biasing hydrogen bond donating host systems towards chemical warfare agent recognition

A series of neutral ditopic and negatively charged, monotopic host molecules have been evaluated for their ability to bind chloride and dihydrogen phosphate anions, and neutral organophosphorus species dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PMP) and the chemical warfare agent (CWA) pinacolyl methylphosphonofluoridate (GD, soman) in organic solvent via hydrogen bonding. Urea, thiourea and boronic acid groups are shown to bind anions and neutral guests through the formation of hydrogen bonds, with the urea and thiourea groups typically exhibiting higher affinity interactions. The introduction of a negative charge on the host structure is shown to decrease anion affinity, whilst still allowing for high stability host-GD complex formation. Importantly, the affinity of the host for the neutral CWA GD is greater than for anionic guests, thus demonstrating the potential for selectivity reversal based on charge repulsion

Editorial: International Women of Supramolecular Chemistry

There is a need to address the lack of diversity in Chemistry (Urbina-Blanco et al., 2020). Despite dedicated programmes and outreach activities to attract individuals from minority backgrounds to initiate their academic studies in this area, at the most senior levels there remains an underrepresentation of minority and marginalised groups (RSC, 2018). People who have one or more protected EDI (Equality, Diversity, Inclusion) characteristic such as race, religion, disability, sexuality, or gender face more barriers to remain and to succeed within science

Supramolecular Self-associating Amphiphiles (SSAs) as enhancers of antimicrobial agents towards Escherichia coli (E. coli)

Supramolecular self-associating amphiphiles (SSAs) are a class of amphiphilic salt which have demonstrated antimicrobial activity against both Gram-positive and Gram-negative bacteria. Herein, we show that SSAs are also able to increase the efficacy of a range of currently used antimicrobial/therapeutic agents with a range of different chemical structures and modes of antimicrobial action against Gram-negative Escherichia coli, which include: octenidine (an antiseptic); ampicillin (an antibiotic); and cisplatin (a DNA chelating agent). Additionally, we show these effects to be dependent on the order of agent addition. Finally, through completion of a range of 1[thin space (1/6-em)]:[thin space (1/6-em)]1 SSA[thin space (1/6-em)]:[thin space (1/6-em)] antimicrobial/therapeutic agent physicochemical studies we gain an understanding as to how the self-association events and resultant SSA aggregate structure are effected by the presence of these secondary molecular species

Supramolecular Chemistry: Young Talents and their Mentors

Celebrating Supramolecular Chemistry and Mentoring: ChemPlusChem is pleased to publish a Special Collection on Supramolecular Chemistry: Young Talents and their Mentors, guest‐edited by Anna McConnell, Cally Haynes, Claudia Caltagirone, and Jennifer Hiscock. The Special Collection features recent developments in supramolecular chemistry and highlights mentoring relationships between emerging investigators and their mentor

Supramolecular self-associating amphiphiles inhibit biofilm formation by the critical pathogens, Pseudomonas aeruginosa and Candida albicans

In 2019, 4.95 million deaths were directly attributed to antimicrobial resistant bacterial infections globally. In addition, the mortality associated with fungal infections is estimated at 1.7 million annually, with many of these deaths attributed to species that are no longer susceptible to traditional therapeutic regimes. Herein, we demonstrate the use of a novel class of supramolecular self-associating amphiphilic (SSA) salts as antimicrobial agents against the critical pathogens Pseudomonas aeruginosa and Candida albicans. We also identify preliminary structure activity relationships for this class of compound that will aid the development of next-generation SSAs demonstrating enhanced antibiofilm activity. To gain insight into the possible mode of action for these agents, a series of microscopy studies were performed, taking advantage of the intrinsic fluorescent nature of benzothiazole substituted SSAs. Analysis of these data showed that the SSAs interact with the cell surface and that a benzothiazole containing SSA inhibits hyphal formation by C. albicans

Towards the Application of Supramolecular Self-Associating Amphiphiles as Next-Generation Delivery Vehicles

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

'Frustrated' hydrogen bonded self-associated systems as templates towards DNA incorporated nanostructure formation

Herein, we present the synthesis of a thymine nucleobase appended ‘frustrated’ monomer, which exhibits self-association in DMSO solutions through the formation of hydrogen bonds. This self-association process has been explored in both competitive DMSO solutions and the solid state, using a combination of NMR and single crystal X-ray diffraction techniques. The self-associative equilibria within the solution state are balanced in such a way that the hydrogen bond donating (HBD) and accepting (HBA) thymine residue present within the monomeric structure is free to coordinate further guest species such as the complimentary DNA base adenine. The adenine simulants, 2-aminopyridine and 2,6-diaminopyridine have been used to explore the potential of these self-associated structures towards the coordination of complimentary DNA base pairs