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http://hdl.handle.net/10773/41339
Title: | Effect of β-cyclodextrin on the CO release kinetics and antimicrobial activity of [NEt4][Mo(CO)5Br] |
Author: | Monteiro, Rodrigo P. Calhau, Isabel B. Gomes, Ana C. Pereira, Carla Vieira, Cátia Faustino, M. Amparo F. Almeida, Adelaide Pillinger, Martyn Romão, Carlos C. Gonçalves, Isabel S. |
Keywords: | Carbon monoxide-releasing molecules β-cyclodextrin Mb assay Antibacterial activity Escherichia coli |
Issue Date: | 1-Nov-2023 |
Publisher: | Elsevier |
Abstract: | In the present work the possibility of improving the solubility, bioavailability and bactericidal activity of the carbon monoxide releasing molecule (CORM) [Mo(CO)5Br]− (as its tetraethylammonium salt) (1) by solvent-free co-grinding with β-cyclodextrin (βCD) in a planetary ball mill was investigated. Data obtained by FT-IR spectroscopy, Raman spectroscopy, powder X-ray diffraction and thermogravimetric analysis showed that, other than a small decrease in the crystallinity of 1, the co-grinding process produced a finely dispersed physical mixture of crystalline CORM and crystalline excipient. The aqueous solubility of 1 in the 1-βCD product was enhanced with respect to sparingly soluble pure 1, which might be ascribed to increased wettability and a CD-CORM interaction in solution. Investigation of the CO release kinetics by the standard myoglobin assay showed that the half-life of CO release increased from ca. 6 min for 1 to ca. 19 min for 1-βCD, while the number of equivalents released decreased from 3.2 to 1.8. The antibacterial properties of 1 and 1-βCD were evaluated using the broth microdilution method to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against the model Gram-negative bacterium, Escherichia coli. The compounds showed similar growth inhibitory (MIC values of 200 μM) and bactericidal (MBC/MIC ≈ 2) effects. Bacterial viability assays corroborated the MBC/MIC studies, showing 3 logs (99.9% of relative light units - RLU) reduction in viable cell count after 15 min exposure to 2 × MIC. Although the CORM-CD system displays a lengthening of the half-life of CO release and a decrease in the CO release efficiency relative to 1, the co-grinding with βCD does not affect the bactericidal activity of the CORM. Overall, the βCD could be a suitable excipient for the development of immediate-release formulations of CORMs like the pentacarbonyl complex 1. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/41339 |
DOI: | 10.1016/j.jorganchem.2023.122844 |
ISSN: | 0022-328X |
Publisher Version: | https://www.sciencedirect.com/science/article/pii/S0022328X23002322?via%3Dihub |
Appears in Collections: | CESAM - Artigos CICECO - Artigos DBio - Artigos DQ - Artigos REQUIMTE - Artigos |
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File | Description | Size | Format | |
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1-s2.0-S0022328X23002322-main.pdf | 794.19 kB | Adobe PDF | View/Open |
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