‘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

Antibacterial compounds

The present invention relates to certain compounds of formula (I) wherein - Ar is (Ar1) or (Ar2) and to their uses as antibacterial agents. The invention further relates to methods of treatment of bacterial infection with such compounds, optionally in combination with other antimicrobials and to compositions and pharmaceutical formulations containing such compounds. The invention additionally relates to coatings containing such compounds and to items having such coatings

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

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

‘Function First’: how to promote physical activity and physical function in people with long-term conditions managed in primary care? A study combining realist and co-design methods

Objectives To develop a taxonomy of interventions and a programme theory explaining how interventions improve physical activity and function in people with long-term conditions managed in primary care. To co-design a prototype intervention informed by the programme theory. Design Realist synthesis combining evidence from a wide range of rich and relevant literature with stakeholder views. Resulting context, mechanism and outcome statements informed co-design and knowledge mobilisation workshops with stakeholders to develop a primary care service innovation. Results A taxonomy was produced, including 13 categories of physical activity interventions for people with long-term conditions. Abridged realist programme theory Routinely addressing physical activity within consultations is dependent on a reinforcing practice culture, and targeted resources, with better coordination, will generate more opportunities to address low physical activity. The adaptation of physical activity promotion to individual needs and preferences of people with long-term conditions helps affect positive patient behaviour change. Training can improve knowledge, confidence and capability of practice staff to better promote physical activity. Engagement in any physical activity promotion programme will depend on the degree to which it makes sense to patients and professions, and is seen as trustworthy. Co-design The programme theory informed the co-design of a prototype intervention to: improve physical literacy among practice staff; describe/develop the role of a physical activity advisor who can encourage the use of local opportunities to be more active; and provide materials to support behaviour change. Conclusions Previous physical activity interventions in primary care have had limited effect. This may be because they have only partially addressed factors emerging in our programme theory. The co-designed prototype intervention aims to address all elements of this emergent theory, but needs further development and consideration alongside current schemes and contexts (including implications relevant to COVID-19), and testing in a future study. The integration of realist and co-design methods strengthened this study

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

Promoting physical activity and physical function in people with long-term conditions by primary care:the Function First realist synthesis with co-design

Background As people age and accumulate long-term conditions, their physical activity and physical function declines, resulting in disability and loss of independence. Primary care is well placed to empower individuals and communities to reduce this decline; however, the best approach is uncertain. Objectives To develop a programme theory to explain the mechanisms through which interventions improve physical activity and physical function in people with long-term conditions in different primary care contexts, and to co-design a prototype intervention. Data sources Systematic literature searches of relevant databases with forwards and backwards citation tracking, grey literature searches and further purposive searches were conducted. Qualitative data were collected through workshops and interviews. Design Realist evidence synthesis and co-design for primary care service innovation. Setting Primary care in Wales and England. Participants Stakeholders included people with long-term conditions, primary care professionals, people working in relevant community roles and researchers. Methods The realist evidence synthesis combined evidence from varied sources of literature with the views, experiences and ideas of stakeholders. The resulting context, mechanism and outcome statements informed three co-design workshops and a knowledge mobilisation workshop for primary care service innovation. Results Five context, mechanism and outcome statements were developed. (1) Improving physical activity and function is not prioritised in primary care (context). If the practice team culture is aligned to the elements of physical literacy (mechanism), then physical activity promotion will become routine and embedded in usual care (outcome). (2) Physical activity promotion is inconsistent and unco-ordinated (context). If specific resources are allocated to physical activity promotion (in combination with a supportive practice culture) (mechanism), then this will improve opportunities to change behaviour (outcome). (3) People with long-term conditions have varying levels of physical function and physical activity, varying attitudes to physical activity and differing access to local resources that enable physical activity (context). If physical activity promotion is adapted to individual needs, preferences and local resources (mechanism), then this will facilitate a sustained improvement in physical activity (outcome). (4) Many primary care practice staff lack the knowledge and confidence to promote physical activity (context). If staff develop an improved sense of capability through education and training (mechanism), then they will increase their engagement with physical activity promotion (outcome). (5) If a programme is credible with patients and professionals (context), then trust and confidence in the programme will develop (mechanism) and more patients and professionals will engage with the programme (outcome). A prototype multicomponent intervention was developed. This consisted of resources to nurture a culture of physical literacy, materials to develop the role of a credible professional who can promote physical activity using a directory of local opportunities and resources to assist with individual behaviour change. Limitations Realist synthesis and co-design is about what works in which contexts, so these resources and practice implications will need to be modified for different primary care contexts. Conclusions We developed a programme theory to explain how physical activity could be promoted in primary care in people with long-term conditions, which informed a prototype intervention. Future work A future research programme could further develop the prototype multicomponent intervention and assess its acceptability in practice alongside existing schemes before it is tested in a feasibility study to inform a future randomised controlled trial. Study registration This study is registered as PROSPERO CRD42018103027. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 16. See the NIHR Journals Library website for further project information. </jats:sec