Development of photoactivatable CO-releasing tricarbonylrhenium(I) complexes and their integration into cellulose nanocrystals in view of antibacterial activity

Abstract

Infections caused by antibiotic-resistant bacteria represent a major public health problem, and efforts continue to be made to seek new ways of addressing this issue. Photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs) could be an alternative solution to conventional antibiotics, but their mechanism of action is complex and still badly known. In the present work, a tricarbonylrhenium(I) complex (Re-Phe(TPP)) was developed, as well as a more hydrophobic analogue substituted by an adamantyl moiety (Re-Ada(TPP)). When irradiated in the near UV, these molecules generate rapidly one molecule of CO, as well as small amounts of singlet oxygen (1O2). Their decarbonylated photoproducts D-Re-Phe(TPP) and D-Re-Ada(TPP) generate only 1O2, on a prolonged period of time. All these complexes were immobilized on a biocompatible cellulose nanocrystal (CNC) matrix, so that only the diffusive species (CO and 1O2) may be the active ones. Finally, the bactericidal activity of all these systems was evaluated on two bacteria strains, causative of the main wound infections. No compound was active against Pseudomonas aeruginosa. Free Re-Phe(TPP) appeared to be a very good antibacterial agent in the dark against Staphylococcus aureus, although the same molecule adsorbed on the CNC material was ineffective, so that its activity was mainly attributed to direct biological effect. The adamantyl derivative Re-Ada(TPP) was more active in the presence of light than in the dark, possibly due to the contribution of CO and 1O2. In contrast, the decarbonylated photoproduct D-Re-Phe(TPP) only showed moderate activity, suggesting that the production of 1O2 is not enough to induce a significant bactericidal effect. This work allows to identify the limits of Re(I) photoCORMs and corresponding nanomaterials, which are still little used in the fight against bacteria, and it provides good indications on how to improve their design.