Highly selective organo-gallium hydroxamate mediated inhibition of antibiotic resistant Klebsiella pneumoniae

Abstract

Five complexes of gallium derived from hydroxamic acids have been synthesised, characterised, and their anti-bacterial activity and mammalian cell toxicity established. These are three metal–organic complexes; [Ga(BPHA)3] 1, [Ga(BHA-H)3] 2, [Ga(SHA-H2)(SHA-H)3] 3, and two heteroleptic organometallic complexes [GaMe2(BPHA)] 4, and [GaMe(BHA-H)2] 5, along with the iron complex [Fe(BPHA)3] 6 (BPHA-H = N-benzoyl-N-phenylhydroxamic acid, BHA-H2 = phenylhydroxamic acid, and SHA-H3 = salicylhydroxamic acid). Solid-state structures of 1, 4–6 were identified by single-crystal X-ray crystallography. Complexes 1 and 6 adopt an octahedral geometry at the metal centre, while the organometallic complexes 4 and 5 adopt, respectively, tetrahedral and trigonal bipyramidal geometry. The solution and solid-state chemistry of complex 3 was found to differ: the solution state is composed of an equilibrium mixture of the bis-complexed hydroximate–hydroxamate species and the homoleptic tris-hydroxamate species, with the solid state preferring the bis-complexed hydroximate–hydroxamate composition. The methyl gallium complexes 4 and 5 differed in their preferred composition with 4 forming the expected dimethyl hydroxamate complex while 5 stabilises as the methyl bis-hydroxamate complex. Complexes were tested for the anti-microbial activity against a series of Gram-positive and Gram-negative bacteria, with an emphasis on the Gram-negative Klebsiella pneumoniae. While the metal–organic complexes 1, 2, 3 and 6 showed little to no activity towards either the bacteria or mammalian cells, the alkyl gallium complexes 4 and 5 were found to have exceptional activity toward K. pneumoniae in RPMI-HS media with MIC values of 78 nM. Interestingly, [GaMe2(OH)] also showed significant activity with an MIC of 156 nM.

Graphical abstract: Highly selective organo-gallium hydroxamate mediated inhibition of antibiotic resistant Klebsiella pneumoniae

Supplementary files

Article information

Article type
Paper
Submitted
28 Aug 2024
Accepted
05 Nov 2024
First published
11 Nov 2024

Dalton Trans., 2025, Advance Article

Highly selective organo-gallium hydroxamate mediated inhibition of antibiotic resistant Klebsiella pneumoniae

R. N. Duffin, J. T. A. Kelderman, M. E. Herdman and P. C. Andrews, Dalton Trans., 2025, Advance Article , DOI: 10.1039/D4DT02440K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements