Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community.

Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three-dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age-associated pathology. The ECM 'Ageing Across the Life Course' interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field.

Tools to enable the study and translation of supramolecular amphiphiles.

This tutorial review focuses on providing a summary of the key techniques used for the characterisation of supramolecular amphiphiles and their self-assembled aggregates; from the understanding of low-level molecular interactions, to materials analysis, use of data to support computer-aided molecular design and finally, the translation of this class of compounds for real world application, specifically within the clinical setting. We highlight the common methodologies used for the study of traditional amphiphiles and build to provide specific examples that enable the study of specialist supramolecular systems. This includes the use of nuclear magnetic resonance spectroscopy, mass spectrometry, X-ray scattering techniques (small- and wide-angle X-ray scattering and single crystal X-ray diffraction), critical aggregation (or micelle) concentration determination methodologies, machine learning, and various microscopy techniques. Furthermore, this review provides guidance for working with supramolecular amphiphiles in in vitro and in vivo settings, as well as the use of accessible software programs, to facilitate screening and selection of druggable molecules. Each section provides: a methodology overview - information that may be derived from the use of the methodology described; a case study - examples for the application of these methodologies; and a summary section - providing methodology specific benefits, limitations and future applications.

Participatory Mathematical Modeling Approach for Policymaking during the First Year of the COVID-19 Crisis, Jordan.

We engaged in a participatory modeling approach with health sector stakeholders in Jordan to support government decision-making regarding implementing public health measures to mitigate COVID-19 disease burden. We considered the effect of 4 physical distancing strategies on reducing COVID-19 transmission and mortality in Jordan during March 2020-January 2021: no physical distancing; intermittent physical distancing where all but essential services are closed once a week; intermittent physical distancing where all but essential services are closed twice a week; and a permanent physical distancing intervention. Modeling showed that the fourth strategy would be most effective in reducing cases and deaths; however, this approach was only marginally beneficial to reducing COVID-19 disease compared with an intermittently enforced physical distancing intervention. Scenario-based model influenced policy-making and the evolution of the pandemic in Jordan confirmed the forecasting provided by the modeling exercise and helped confirm the effectiveness of the policy adopted by the government of Jordan.

An artesunate pharmacometric model to explain therapeutic responses in falciparum malaria.

BACKGROUND: The artemisinins are potent and widely used antimalarial drugs that are eliminated rapidly. A simple concentration-effect pharmacometric model does not explain why dosing more frequently than once daily fails to augment parasite clearance and improve therapeutic responses in vivo. Artemisinins can induce a temporary non-replicative or 'dormant' drug refractory state in Plasmodium falciparum malaria parasites which may explain recrudescences observed in clinical trials despite full drug susceptibility, but whether it explains the dosing-response relationship is uncertain. OBJECTIVES: To propose a revised model of antimalarial pharmacodynamics that incorporates reversible asexual parasite injury and temporary drug refractoriness in order to explain the failure of frequent dosing to augment therapeutic efficacy in falciparum malaria. METHODS: The model was fitted using a Bayesian Markov Chain Monte Carlo approach with the parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from western Cambodia and 40 patients from northwestern Thailand reported previously. RESULTS: The revised model captured the dynamics of parasite clearance data. Its predictions are consistent with observed therapeutic responses. CONCLUSIONS: A within-host pharmacometric model is proposed in which it is hypothesized that some malaria parasites enter a temporary drug refractory state after exposure to artemisinin antimalarials, which is followed by delayed parasite death or reactivation. The model fitted the observed sequential parasite density data from patients with acute P. falciparum malaria, and it supported reduced ring stage activity in artemisinin-resistant infections.

Ultrasound-guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice.

AIMS: Our aim was to determine if ultrasound-guided HPV injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans. METHODS: Fluorescent-polymer microparticles (20 µm) were injected (27G-needle) into the HPV via open laparotomy (n = 4) or under ultrasound-guidance (n = 4) using an MX550D-transducer with a Vevo3100-scanner (FUJIFILM VisualSonics, Inc.). Mice were culled 24-h post injection; organs were frozen, step sectioned (10 µm-slices) and 10 sections/mouse (50 µm-spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy. RESULTS: Murine HPV injection, via open laparotomy-route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound-guided injection resulted in reduced microparticle delivery (p < 0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median (interquartile range) 4.15 (0.00-4.15) versus 0.00 (0.00-0.00) particle-count mm-2 , respectively. CONCLUSIONS: Ultrasound-guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy HPV injection, and high variability in microparticle-counts detected between mice. Ultrasound-guided injection is not currently a technique that can replace open laparotomy HPV of islet transplantation in mice.

The clinical effectiveness of mepolizumab treatment in severe eosinophilic asthma; outcomes from four years cohort evaluation.

BACKGROUND: Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. METHODS: we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. RESULTS: a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period.The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). CONCLUSIONS: mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity.

Insights into rural generalist therapeutic reasoning using a simulated multi-patient emergency scenario.

INTRODUCTION: Therapeutic reasoning focuses on the decisions related to patient disposition and management. This is in contrast to diagnostic reasoning, which is the focus of much of the current discourse in the medical literature. Few studies relate to therapeutic reasoning, and even fewer relate to the rural and remote context. This project sought to explore the therapeutic reasoning used by rural generalists working in a small rural hospital setting in Australia, caring for patients for whom it was unclear if escalation of care, including admission or interhospital transfer, was needed. METHODS: This study was conducted using an interpretivist approach. A simulation scenario was developed with rural generalists and experts in medical simulation to use as a test bed to explore the reasoning of the rural generalist participants. The simulation context was a small rural Australian hospital with resources and treatment options typical of those found in a similar real-life setting. A simulated patient and a registered nurse were embedded in the scenario. Participants needed to make decisions throughout the scenario regarding the simulated patient and two anticipated patients who were said to be coming to the department. The scenario was immediately followed by a semi-structured interview exploring participants' therapeutic reasoning when planning care for these three patients. An inductive content analysis approach was used to analyse the data, and a mental model was developed. The researchers then tested this mental model against the recordings of the participants' simulation scenarios. RESULTS: Eight rural generalists, with varying levels of experience, participated in this study. Through the semi-structured interviews, participants described five themes: assessing clinician capacity to manage patient needs; availability of local physical resources and team members; considering options for help when local management was not enough; patients' wishes and shared decision making; and anticipating future requirements. The mental model developed from these themes consisted of seven questions: 'What can I do for this patient locally and what are my limits?'; 'Who is in my team and who can I rely on?'; 'What are the advantages and disadvantages of local management vs transfer?'; 'Who else needs to be involved and what are their limits?;' 'How can we align the patient's wants with their needs?'; 'How do we adapt to the current and future situation?'; and 'How do I preserve the capacity of the health service to provide care?' CONCLUSION: This study explored the therapeutic reasoning of rural generalists using a simulated multi-patient emergency scenario. The mental model developed serves as a starting point when discussing therapeutic reasoning and is likely to be useful when providing education to medical students and junior doctors who are working in rural and remote contexts where resources and personnel may be limited.

Levels of SARS-CoV-2 population exposure are considerably higher than suggested by seroprevalence surveys.

Accurate knowledge of prior population exposure has critical ramifications for preparedness plans for future SARS-CoV-2 epidemic waves and vaccine prioritization strategies. Serological studies can be used to estimate levels of past exposure and thus position populations in their epidemic timeline. To circumvent biases introduced by the decay in antibody titers over time, methods for estimating population exposure should account for seroreversion, to reflect that changes in seroprevalence measures over time are the net effect of increases due to recent transmission and decreases due to antibody waning. Here, we present a new method that combines multiple datasets (serology, mortality, and virus positivity ratios) to estimate seroreversion time and infection fatality ratios (IFR) and simultaneously infer population exposure levels. The results indicate that the average time to seroreversion is around six months, IFR is 0.54% to 1.3%, and true exposure may be more than double the current seroprevalence levels reported for several regions of England.

Supramolecular self-associating amphiphiles as aqueous pollutant scavengers.

We present a series of supramolecular self-associated amphiphiles, which spontaneously self-assemble into aggregated species. These aggregates are shown to absorb a variety of (polar) micropollutants from aqueous mixtures and as a result we determine the suitability for this technology to be developed further as aqueous environmental clean-up agents.

Supramolecular self-associating amphiphiles: determination of molecular self-association properties and calculation of critical micelle concentration using a high-throughput, optical density based methodology.

Supramolecular self-associating amphiphiles are a class of amphiphilic salt, the anionic component of which is 'frustrated' in nature, meaning multiple hydrogen bonding modes can be accessed simultaneously. Here we derive critical micelle concentration values for four supramolecular self-associating amphiphiles using the standard pendant drop approach and present a new high-throughput, optical density measurement based methodology, to enable the estimation of critical micelle concentrations over multiple temperatures. In addition, we characterise the low-level hydrogen bonded self-association events in the solid state, through single crystal X-ray diffraction, and in polar organic DMSO-d6 solutions using a combination of 1H NMR techniques. Moving into aqueous ethanol solutions (EtOH/H2O or EtOH/D2O (1 : 19 v/v)), we also show these amphiphilic compounds to form higher-order self-associated species through a combination of 1H NMR, dynamic light scattering and zeta potential studies.

The assembly effect: the connectedness between populations is a double-edged sword for public health interventions.

BACKGROUND: Many public health interventions lead to disruption or decrease of transmission, providing a beneficial effect for people in the population regardless of whether or not they individually participate in the intervention. This protective benefit has been referred to as a herd or community effect and is dependent on sufficient population participation. In practice, public health interventions are implemented at different spatial scales (i.e., at the village, district, or provincial level). Populations, however defined (i.e., neighbourhoods, villages, districts) are frequently connected to other populations through human movement or travel, and this connectedness can influence potential herd effects. METHODS: The impact of a public health intervention (mass drug administration for malaria) was modelled, for different levels of connectedness between populations that have similar disease epidemiology (e.g., two nearby villages which have similar baseline malaria incidences and similar malaria intervention measures), or between populations of varying disease epidemiology (e.g., two nearby villages which have different baseline malaria incidences and/or malaria intervention measures). RESULTS: The overall impact of the interventions deployed could be influenced either positively (adding value to the intervention) or negatively (reducing the impact of the intervention) by how much the intervention units are connected with each other (e.g., how frequent people go to the other village or town) and how different the disease intensity between them are. This phenomenon is termed the "assembly effect", and it is a meta-population version of the more commonly understood "herd effect". CONCLUSIONS: The connectedness of intervention units or populations is an important factor to be considered to achieve success in public health interventions that could provide herd effects. Appreciating the assembly effect can improve the cost-effective strategies for global disease elimination projects.

Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination.

BACKGROUND: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost-benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. METHODS: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. RESULTS: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018-2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. CONCLUSIONS: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.

Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.

Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polymerase chain reaction if treatment levels are high and screening is conducted during the dry season. Along with other factors, such as coverage, choice of drug, timing of the intervention, importation of infections, and seasonality, the sensitivity of the diagnostic can play a part in increasing the chance of interrupting transmission.

Macrophage phenotype in response to ECM bioscaffolds.

Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (MECM) is distinct from both the classically activated IFNγ+LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an MECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers.

Estimating the programmatic cost of targeted mass drug administration for malaria in Myanmar.

BACKGROUND: Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar. METHODS: We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses. RESULTS: The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5. CONCLUSION: This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages.

The Role of Low-Energy Electron Interactions in cis-Pt(CO)2Br2 Fragmentation.

Platinum coordination complexes have found wide applications as chemotherapeutic anticancer drugs in synchronous combination with radiation (chemoradiation) as well as precursors in focused electron beam induced deposition (FEBID) for nano-scale fabrication. In both applications, low-energy electrons (LEE) play an important role with regard to the fragmentation pathways. In the former case, the high-energy radiation applied creates an abundance of reactive photo- and secondary electrons that determine the reaction paths of the respective radiation sensitizers. In the latter case, low-energy secondary electrons determine the deposition chemistry. In this contribution, we present a combined experimental and theoretical study on the role of LEE interactions in the fragmentation of the Pt(II) coordination compound cis-PtBr2(CO)2. We discuss our results in conjunction with the widely used cancer therapeutic Pt(II) coordination compound cis-Pt(NH3)2Cl2 (cisplatin) and the carbonyl analog Pt(CO)2Cl2, and we show that efficient CO loss through dissociative electron attachment dominates the reactivity of these carbonyl complexes with low-energy electrons, while halogen loss through DEA dominates the reactivity of cis-Pt(NH3)2Cl2.

A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity.

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.

Algorithm in the Diagnosis of Febrile Illness Using Pathogen-specific Rapid Diagnostic Tests.

BACKGROUND: In the absence of proper guidelines and algorithms, available rapid diagnostic tests (RDTs) for common acute undifferentiated febrile illnesses are often used inappropriately. METHODS: Using prevalence data of 5 common febrile illnesses from India and Cambodia, and performance characteristics (sensitivity and specificity) of relevant pathogen-specific RDTs, we used a mathematical model to predict the probability of correct identification of each disease when diagnostic testing occurs either simultaneously or sequentially in various algorithms. We developed a web-based application of the model so as to visualize and compare output diagnostic algorithms when different disease prevalence and test performance characteristics are introduced. RESULTS: Diagnostic algorithms with appropriate sequential testing predicted correct identification of etiology in 74% and 89% of patients in India and Cambodia, respectively, compared with 46% and 49% with simultaneous testing. The optimally performing sequential diagnostic algorithms differed in India and Cambodia due to varying disease prevalence. CONCLUSIONS: Simultaneous testing is not appropriate for the diagnosis of acute undifferentiated febrile illnesses with presently available tests, which should deter the unsupervised use of multiplex diagnostic tests. The implementation of adaptive algorithms can predict better diagnosis and add value to the available RDTs. The web application of the model can serve as a tool to identify the optimal diagnostic algorithm in different epidemiological settings, while taking into account the local epidemiological variables and accuracy of available tests.

Dissociation of the FEBID precursor cis-Pt(CO)2Cl2 driven by low-energy electrons.

In this study, we present experimental and theoretical results on dissociative electron attachment and dissociative ionisation for the potential FEBID precursor cis-Pt(CO)2Cl2. UHV surface studies have shown that high purity platinum deposits can be obtained from cis-Pt(CO)2Cl2. The efficiency and energetics of ligand removal through these processes are discussed and experimental appearance energies are compared to calculated thermochemical thresholds. The present results demonstrate the potential effectiveness of electron-induced reactions in the deposition of this FEBID precursor, and these are discussed in conjunction with surface science studies on this precursor and the design of new FEBID precursors.

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.