Water soluble organometallic small molecules as promising antibacterial agents: synthesis, physical–chemical properties and biological evaluation to tackle bacterial infections
Metadatos
Afficher la notice complèteEditorial
Royal Society of Chemistry
Date
2022-04-06Referencia bibliográfica
Dalton Trans., 2022, Advance Article. DOI: [10.1039/d2dt01015a]
Patrocinador
Spanish Government PID2019-106832RB-100 SAF2017-82261-P; Generalitat de Catalunya; General Electric 2017SGR1720; DOC-FAM program under the Marie Sklodowska-Curie grant 754397Résumé
The Na[3,3’-Fe(8-I-1,2-C2B9H10)2] and Na[2,2’-M(1,7-C2B9H11)] (M = Co3+, Fe3+) small molecules are synthesized
and the X-ray structures of [(H3O)(H2O)5][2,2’-Co(1,7-C2B9H11)2] and [Cs(MeCN)][8,8’-I2-Fe(1,2
C2B9H10)2], both displaying a transoid conformation of the [M(C2B9)2]− framework, are reported.
Importantly, the supramolecular structure of [(H3O)(H2O)5][2,2’-Co(1,7-C2B9H11)2] presents 2D layers leading to
a lamellar arrangement of the anions while the cation layers form polymeric water rings made of six- and fourmembered
rings of water molecules connected via OH⋯H hydrogen bonds; B–H⋯O contacts connect the
cationic and anionic layers. Herein, we highlight the influence of the ligand isomers (ortho-/meta-), the metal
effect (Co3+/Fe3+) on the same isomer, as well as the influence of the presence of the iodine atoms on the
physical–chemical and biological properties of these molecules as antimicrobial agents to tackle antibioticresistant
bacteria, which were tested with four Gram-positive bacteria, five Gram-negative bacteria, and three
Candida albicans strains that have been responsible for human infections. We have demonstrated an antimicrobial
effect against Candida species (MIC of 2 and 3 nM for Na[3,3’-Co(8-I-1,2-C2B9H10)2] and Na[2,2’-Co
(1,7-C2B9H11)2], respectively), and against Gram-positive and Gram-negative bacteria, including multiresistant
MRSA strains (MIC of 6 nM for Na[3,3’-Co(8-I-1,2-C2B9H10)2]). The selectivity index for antimicrobial activity of
Na[3,3’-Co(1,2-C2B9H11)2] and Na[3,3’-Co(8-I-1,2-C2B9H10)2] compounds is very high (165 and 1180, respectively),
which reveals that these small anionic metallacarborane molecules may be useful to tackle antibioticresistant
bacteria. Moreover, we have demonstrated that the outer membrane of Gram-negative bacteria constitutes
an impermeable barrier for the majority of these compounds. Nonetheless, the addition of two iodine
groups in the structure of the parent Na[3,3’-Co(1,2-C2B9H11)2] had an improved effect (3–7 times) against
Gram-negative bacteria. Possibly the changes in their physical–chemical properties make the meta-isomers
and the ortho-di-iodinated small molecules more permeable for crossing this barrier. It should be emphasized
that the most active metallabis(dicarbollide) small molecules are both transoid conformers in contrast to the
ortho- [3,3’-Co(1,2-C2B9H11)2]− that is cisoid. The fact that these small molecules cross the mammalian membrane
and have antimicrobial properties but low toxicity for mammalian cells (high selectivity index, SI) represents
a promising tool to treat infectious intracellular bacteria. Since there is an urgent need for antibiotic discovery
and development, this study represents a relevant advance in the field.