Adamantane appended antimicrobial supramolecular self-associating amphiphiles

Andzelika Rutkauskaite; Lisa J. White; Jessica E. Boles; Kira L.F. Hilton; Melanie Clifford; Bethany Patenall; Bree R. Streather; Daniel P. Mulvihill; Samantha A. Henry; Mark Shepherd; J. Mark Sutton; Charlotte K. Hind; Jennifer R. Hiscock

doi:10.1080/10610278.2022.2161902

Adamantane appended antimicrobial supramolecular self-associating amphiphiles

Andzelika Rutkauskaite, Lisa J. White, Jessica E. Boles, Kira L.F. Hilton, Melanie Clifford, Bethany Patenall, Bree R. Streather, Daniel P. Mulvihill, Samantha A. Henry, Mark Shepherd, J. Mark Sutton, Charlotte K. Hind, Jennifer R. Hiscock^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d ₆ 0.5% H₂O and H₂O (D₂O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of ¹H NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of ¹H NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents.

Original language	English
Pages (from-to)	677-686
Number of pages	10
Journal	Supramolecular Chemistry
Volume	33
Issue number	12
DOIs	https://doi.org/10.1080/10610278.2022.2161902
Publication status	Published - 2021

Bibliographical note

Funding Information:
A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship.

Funding Information:
This work was supported by the UKHSA [PhD studentship funding]; UK Research and Innovation [MR/T020415/1]. A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship.

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

Hydrogen bond
amphiphile
antimicrobial
self-association

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10.1080/10610278.2022.2161902

Cite this

Rutkauskaite, A., White, L. J., Boles, J. E., Hilton, K. L. F., Clifford, M., Patenall, B., Streather, B. R., Mulvihill, D. P., Henry, S. A., Shepherd, M., Sutton, J. M., Hind, C. K., & Hiscock, J. R. (2021). Adamantane appended antimicrobial supramolecular self-associating amphiphiles. Supramolecular Chemistry, 33(12), 677-686. https://doi.org/10.1080/10610278.2022.2161902

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abstract = "Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d 6 0.5% H2O and H2O (D2O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of 1H NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of 1H NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents.",

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note = "Funding Information: A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship. Funding Information: This work was supported by the UKHSA [PhD studentship funding]; UK Research and Innovation [MR/T020415/1]. A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

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doi = "10.1080/10610278.2022.2161902",

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AU - Clifford, Melanie

AU - Patenall, Bethany

AU - Streather, Bree R.

AU - Mulvihill, Daniel P.

AU - Henry, Samantha A.

AU - Shepherd, Mark

AU - Sutton, J. Mark

AU - Hind, Charlotte K.

AU - Hiscock, Jennifer R.

N1 - Funding Information: A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship. Funding Information: This work was supported by the UKHSA [PhD studentship funding]; UK Research and Innovation [MR/T020415/1]. A. Rutkauskaite, L.White, J.Boles, K. Hilton and J. Hiscock would like to thank the University of Kent for funding. Additionally, J. Hiscock and L. White would also like to thank UKRI for the funding of J. Hiscock's Future Leaders Fellowship (MR/T020415/1). J. Boles thank UKHSA for the funding of her PhD studentship. Publisher Copyright: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2021

Y1 - 2021

N2 - Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d 6 0.5% H2O and H2O (D2O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of 1H NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of 1H NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents.

AB - Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d 6 0.5% H2O and H2O (D2O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of 1H NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of 1H NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents.

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SN - 1061-0278

VL - 33

SP - 677

EP - 686

JO - Supramolecular Chemistry

JF - Supramolecular Chemistry

IS - 12

ER -

Adamantane appended antimicrobial supramolecular self-associating amphiphiles

Abstract

Bibliographical note

Keywords

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