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-
/0.5% H
O). However, extended self-associated aggregates are observed to form under aqueous conditions (H
O/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.
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 (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
, 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 : 1 SSA : 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.
The activity of membrane proteins and compounds that interact with the membrane is modulated by the surrounding lipid composition. However, there are no simple methods that determine the composition ...of these annular phospholipids in eukaryotic systems. Herein, we describe a simple methodology that enables the identification and quantification of the lipid composition around membrane-associated compounds using SMA-nanodiscs and routine
H-
P NMR.
While cancer now impacts the health and well-being of more of the human population than ever before, the exponential rise in antimicrobial resistant (AMR) bacterial infections means AMR is predicted ...to become one of the greatest future threats to human health. It is therefore vital that novel therapeutic strategies are developed that can be used in the treatment of both cancer and AMR infections. Whether the target of a therapeutic agent be inside the cell or in the cell membrane, it must either interact with or cross this phospholipid barrier to elicit the desired cellular effect. Here we summarise findings from published research into the phospholipid membrane composition of bacterial and cancer cell lines and biological samples from cancer patients. These data not only highlight key differences in the membrane composition of these biological samples, but also the methods used to elucidate and report the results of this analogous research between the microbial and cancer fields.
This review acts as a repository and comparison of cell membrane phospholipid composition data collected from microbial and cancer fields.
Synthetic ionophores are promising therapeutic targets, yet poor water solubility limits their potential for translation into the clinic. Here we report a water-soluble, supramolecular ...self-associating amphiphile that functions as a cation uniporter in synthetic vesicle systems, deriving mechanistic insight through planar bilayer patch clamp experiments.
Synthetic ionophores are promising therapeutic targets, yet poor water solubility limits their potential for translation into the clinic. Here we report a water soluble, supramolecular self-associating amphiphile (SSA) with cation transport function.
Herein, we report a series of di-anionic supramolecular self-associating amphiphiles (SSAs). We elucidate the antimicrobial properties of these SSAs against both methicillin resistant
and
. In ...addition, we show this class of compound to form both intra- and intermolecular hydrogen bonded macrocyclic structures in the solid state.
Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules ...that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis
versus
either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells.
Herein we show the potential SSA technology towards the development of synergistic next-generation anticancer treatments.
Herein we report 50 structurally related supramolecular self‐associating 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, gas‐phase, 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 property‐antimicrobial activity relationships for our model Gram‐negative and Gram‐positive bacteria, while simultaneously providing insight towards the elucidation of SSA mode of antimicrobial action.
The antimicrobial efficacy of 50 supramolecular self‐associating salts (SSAs) and related compounds was established against MRSA and E. coli. In addition, 14 different physicochemical properties were determined experimentally for each compound within this library. From these data we identified relationships between compound structure, physiochemical property, and antimicrobial activity.
Here we present the synthesis of complementary (pseudo) nucleobase appended Supramolecular Self-associating Amphiphilic (SSA) salts and, establish the potential for this molecular construct to ...produce a new class of DNA inspired synthetic structures/materials. The anionic component of this class of amphiphile contains multiple hydrogen bond donating and accepting functionalities, meaning that these systems can access multiple self-associative hydrogen-bonding modes simultaneously. Herein, we characterise the self-associative properties of these DNA inspired amphiphiles in the solid state, solution state and gas phase. Finally, we investigate the potential of these amphiphilic salts to act as antimicrobial agents against model Gram-positive (methicillin-resistant Staphylococcus aureus - MRSA) and Gram-negative (Escherichia coli - E. coli) bacteria.
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