RESUMO
cis- and trans-(Cl,Cl)-[RuII(FT)Cl2(NO)](PF6) complexes show efficient NO photodelivery upon two-photon excitation in the NIR region. Moreover, cytotoxicity and phototoxicity studies provide evidence that these complexes are promising candidates as photoactivatable molecular tools for resection of malignancies.
Assuntos
Antineoplásicos/química , Raios Infravermelhos , Óxido Nítrico/metabolismo , FototerapiaRESUMO
The synthesis and behavior in water of a set of various cis(Cl,Cl)-[R-tpyRuCl2(NO)](PF6) and trans(Cl,Cl)-[R-tpyRuCl2(NO)](PF6) (R = fluorenyl, phenyl, thiophenyl; tpy = 2,2':6',2''-terpyridine) complexes are presented. In any case, one chlorido ligand is substituted by a hydroxo ligand and the final species arises as a single trans(NO,OH) isomer, whatever the nature of the starting cis/trans(Cl,Cl) complexes. Six X-ray crystal structures are presented for cis(Cl,Cl)-[thiophenyl-tpyRuCl2(NO)](PF6) (cis-3a), trans(Cl,Cl)-[thiophenyl-tpyRuCl2(NO)](PF6) (trans-3a), trans(NO,OH)-[phenyl-tpyRu(Cl)(OH)(NO)](PF6) (4a), trans(NO,OH)-[thiophenyl-tpyRu(Cl)(OH)(NO)](PF6) (4b), trans(NO,OEt)-[phenyl-tpyRu(Cl)(OEt)(NO)](PF6) (5a), and trans(NO,OH)-[phenyl-tpyRu(Cl)(OEt)(NO)](PF6) (5b) compounds. The different cis/trans(Cl,Cl) complexes exhibit an intense low-lying transition in the λ = 330-390 nm range, which appears to be slightly blue-shifted after Cl â OH substitution. In water, both cis/trans(Cl,Cl) isomers are converted to a single trans(NO,OH) isomer in which one chlorido- is replaced by one hydroxo-ligand, which avoids tedious separation workout. The water stable trans(NO,OH)-species all release NO with quantum yields of 0.010 to 0.075 under irradiation at 365 nm. The properties are discussed with computational analysis performed within the framework of Density Functional Theory.
RESUMO
Antibiotic resistance is becoming a global scourge with 700,000 deaths each year and could cause up to 10 million deaths by 2050. As an example, Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. S. epidermidis can form biofilms, which contribute to its pathogenicity when present in intravascular devices. These staphylococci, embedded in the biofilm matrix, are resistant to methicillin, which had long been the recommended therapy and which has nowadays been replaced by less toxic and more stable therapeutic agents. Moreover, current reports indicate that 75 to 90% of Staphylococcus epidermidis isolates from nosocomial infections are methicillin-resistant strains. The challenge of successfully combating antibiotics resistance in biofilms requires the use of compounds with a controlled mode of action that can act in combination with antibiotics. Ruthenium nitrosyl complexes are potential systems for NO release triggered by light. The influence of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) on Staphylococcus epidermidis resistant to methicillin is described. The results show a 50% decrease in cell viability in bacteria treated with low concentrations of NO. When combined with methicillin, this low dose of NO dramatically decreases bacterial resistance and makes bacteria 100-fold more sensitive to methicillin.
Assuntos
Biofilmes/efeitos dos fármacos , Resistência a Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/farmacologia , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Rutênio/química , Rutênio/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/patogenicidadeRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.