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. 2022 Jan 25:9:815827.
doi: 10.3389/fchem.2021.815827. eCollection 2021.

Silver(I)-Tazobactam Frameworks with Improved Antimicrobial Activity

Daniela R Ferreira  1   2 , Paula C Alves  1   2 , Alexander M Kirillov  1 , Patrícia Rijo  3   4 , Vânia André  1   2
Affiliations

Silver(I)-Tazobactam Frameworks with Improved Antimicrobial Activity

Daniela R Ferreira et al. Front Chem. .

Abstract

Tazobactam (TazoH) is a penicillinate sulfone β-lactamase inhibitor with negligible antimicrobial activity, commonly used with other antibiotics to provide an effective combination against many susceptible organisms expressing β-lactamases. Two novel Ag(I)-tazobactam frameworks ([Ag(I)-Tazo] and [Ag(I)-Tazo2]) prepared by mechanochemistry are presented herein as alternative forms to improve the antimicrobial activity of tazobactam by exploring synergistic effects with silver, being the first crystal structures reported of tazobactam coordinating to a metal site. The topological analysis of the 3D ([Ag(I)-Tazo]) and 2D+1D ([Ag(I)-Tazo2]) frameworks revealed underlying nets with the cbs (CrB self-dual) and decorated sql topologies, respectively. These novel frameworks are stable and show an enhanced antimicrobial activity when compared to tazobactam alone. Amongst the tested microorganisms, Pseudomonas aeruginosa is the most sensitive to tazobactam and the new compounds. This study thus unveils novel facets of tazobactam chemistry and opens up its application as a multifunctional linker for the design of antibiotic coordination frameworks and related materials.

Keywords: antibiotic coordination frameworks; mechanochemistry; silver; supramolecular chemistry; tazobactam.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Tazobactam (TazoH) representation.
FIGURE 2
FIGURE 2
Schematic representation of (A) the coordination sites and (B) the coordination geometry around the Ag(I) sites (hydrogen atoms have been omitted for clarity reasons) for [Ag(I)-Tazo].
FIGURE 3
FIGURE 3
Crystal packing of [Ag(I)-Tazo], depicting (A) the view along the b axis, and (B) the formation of the 3D metal-organic framework.
FIGURE 4
FIGURE 4
Topological representation of a dinodal 3,4-linked net in [Ag(I)-Tazo] with a cbs (CrB self-dual) topology; rotated view along the b axis; Ag1/Ag2 centers (gray balls), centroids of µ3-and µ4-Tazo− moieties (yellow).
FIGURE 5
FIGURE 5
Schematic representation of (A) the coordination sites and (B) the coordination geometry around the Ag(I) sites (hydrogen atoms have been omitted for clarity reasons) for [Ag(I)-Tazo2].
FIGURE 6
FIGURE 6
Crystal packing of [Ag(I)-Tazo2] depicting the 2D (blue) and 1D (green) coordination networks.
FIGURE 7
FIGURE 7
Topological representation of a mononodal 4-linked metal-organic layer in [Ag(I)-Tazo2] with a sql topology, decorated with 2C1 chains; rotated view along the b axis; Ag1/Ag2 centers (gray balls), centroids of TazoH/Tazo− moieties (yellow).
FIGURE 8
FIGURE 8
Hirshfeld surface mapped with dnorm, with surfaces shown as transparent to allow the visualization of the compound (A) and two-dimensional fingerprint plots (B) for the most relevant interactions in [Ag(I)-Tazo] (C) and [Ag(I)-Tazo2] (D).
FIGURE 9
FIGURE 9
(A) Differential scanning calorimetry (DSC) and thermogravimetry (TGA) and (B) hot-stage microscopy (HSM) images at 23, 155 and 227°C for compound [Ag(I)-Tazo2].
FIGURE 10
FIGURE 10
Minimum inhibitory concentration values (MIC, µg/ml) of the synthesized compounds {[Ag(I)-Tazo] and [Ag(I)-Tazo2]} and the starting materials for Candida albicans and Saccharomyces cerevisiae (yeasts), Escherichia coli and Pseudomonas aeruginosa (Gram-negative bacteria) and Staphylococcus aureus, Enterococcus faecalis and Mycobacterium smegmatis (Gram-positive bacteria) after 24 h for bacteria and 48 h for yeasts. DMSO was used as negative control and nystatin, norfloxacin and vancomycin were used as positive controls for yeasts, Gram-negative and Gram-positive bacteria, respectively.
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