Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

Anita Toscani; Charlotte Hind; Melanie Clifford; Seong Heun Kim; Antonia Gucic; Charlotte Woolley; Naima Saeed; Khondaker Miraz Rahman; J. Mark Sutton; Daniele Castagnolo

doi:10.1016/j.ejmech.2021.113172

Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

Anita Toscani, Charlotte Hind, Melanie Clifford, Seong Heun Kim, Antonia Gucic, Charlotte Woolley, Naima Saeed, Khondaker Miraz Rahman, J. Mark Sutton, Daniele Castagnolo^*

^*Corresponding author for this work

Institute of Pharmaceutical Science

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

13 Citations (Scopus)

Abstract

The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-[Mn(N^∧N)(CO)₃(L)] have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435–450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1–3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1–2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4–8 μg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments.

Original language	English
Article number	113172
Journal	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume	213
DOIs	https://doi.org/10.1016/j.ejmech.2021.113172
Publication status	Published - 5 Mar 2021

Keywords

antibacterial
biofilm
Carbon monoxide
CORM
photoactivation

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10.1016/j.ejmech.2021.113172

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Toscani, A., Hind, C., Clifford, M., Kim, S. H., Gucic, A., Woolley, C., Saeed, N., Rahman, K. M., Sutton, J. M., & Castagnolo, D. (2021). Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 213, Article 113172. https://doi.org/10.1016/j.ejmech.2021.113172

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title = "Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms",

abstract = "The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-[Mn(N∧N)(CO)3(L)] have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435–450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1–3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1–2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4–8 μg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments.",

keywords = "antibacterial, biofilm, Carbon monoxide, CORM, photoactivation",

author = "Anita Toscani and Charlotte Hind and Melanie Clifford and Kim, {Seong Heun} and Antonia Gucic and Charlotte Woolley and Naima Saeed and Rahman, {Khondaker Miraz} and Sutton, {J. Mark} and Daniele Castagnolo",

note = "Funding Information: University of London is gratefully acknowledged for the CW Maplethorpe Fellowship to AT. NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research, NC/T001240/1) is acknowledged for research funding. Publisher Copyright: {\textcopyright} 2021 Elsevier Masson SAS Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

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doi = "10.1016/j.ejmech.2021.113172",

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Toscani, A, Hind, C, Clifford, M, Kim, SH, Gucic, A, Woolley, C, Saeed, N, Rahman, KM, Sutton, JM & Castagnolo, D 2021, 'Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms', EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 213, 113172. https://doi.org/10.1016/j.ejmech.2021.113172

TY - JOUR

T1 - Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

AU - Toscani, Anita

AU - Hind, Charlotte

AU - Clifford, Melanie

AU - Kim, Seong Heun

AU - Gucic, Antonia

AU - Woolley, Charlotte

AU - Saeed, Naima

AU - Rahman, Khondaker Miraz

AU - Sutton, J. Mark

AU - Castagnolo, Daniele

N1 - Funding Information: University of London is gratefully acknowledged for the CW Maplethorpe Fellowship to AT. NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research, NC/T001240/1) is acknowledged for research funding. Publisher Copyright: © 2021 Elsevier Masson SAS Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/5

Y1 - 2021/3/5

N2 - The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-[Mn(N∧N)(CO)3(L)] have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435–450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1–3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1–2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4–8 μg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments.

AB - The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-[Mn(N∧N)(CO)3(L)] have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435–450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1–3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1–2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4–8 μg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments.

KW - antibacterial

KW - biofilm

KW - Carbon monoxide

KW - CORM

KW - photoactivation

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U2 - 10.1016/j.ejmech.2021.113172

DO - 10.1016/j.ejmech.2021.113172

M3 - Article

AN - SCOPUS:85099851561

SN - 0223-5234

VL - 213

JO - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

M1 - 113172

ER -

Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

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