TY - JOUR
T1 - Effect of β-cyclodextrin on the CO release kinetics and antimicrobial activity of [NEt4][Mo(CO)5Br]
AU - Monteiro, Rodrigo P.
AU - Calhau, Isabel B.
AU - Gomes, Ana C.
AU - Pereira, Carla
AU - Vieira, Cátia
AU - Faustino, M. Amparo F．
AU - Almeida, Adelaide
AU - Pillinger, Martyn
AU - Romão, Carlos C.
AU - Gonçalves, Isabel S.
N1 - Funding Information:
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020), LAQV-REQUIMTE ( UIDB/50006/2020 and UIDP/50006/2020 ), and CESAM (UIDB/50017/202 and UIDP/50017/2020), financed by national funds through the FCT (Fundação para a Ciência e a Tecnologia) / MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) (PIDDAC). I.B.C. (ref. 2021.05953.BD ), R.P.M. (ref. 2020.04758.BD ), and C.V. (ref. SFRH/BD/150358/2019 ) are grateful to the FCT and the European Social Fund (ESF) for PhD grants. A.C.G. ( CEECIND/02128/2017 ) thanks the FCT/MCTES for funding through the Individual Call to Scientific Employment Stimulus.
Publisher Copyright:
© 2023
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
KW - Antibacterial activity
KW - Carbon monoxide-releasing molecules
KW - Escherichia coli
KW - Mb assay
KW - β-cyclodextrin
UR - http://www.scopus.com/inward/record.url?scp=85169910387&partnerID=8YFLogxK
U2 - 10.1016/j.jorganchem.2023.122844
DO - 10.1016/j.jorganchem.2023.122844
M3 - Article
AN - SCOPUS:85169910387
SN - 0022-328X
VL - 1000
JO - Journal of Organometallic Chemistry
JF - Journal of Organometallic Chemistry
M1 - 122844
ER -