5-Nitroimidazole (5NIMH), chosen as a molecular model of nitroimidazole derivatives, which represent a broadspectrum class of antimicrobials, was incorporated into the ruthenium complexes [Ru(tpy)(phen)(5NIM)]PF 6 (1) and [Ru(tpy)(dmp)(5NIM)]PF 6 (2) (tpy = terpyridine, phen = phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline). Besides the uncommon metal coordination of 5-nitroimidazole in its imidazolate form (5NIM), the different architectures of the spectator ligands (phen and dmp) were exploited to tune the "mode of action" of the resulting complexes, passing from a photostable compound where the redox properties of 5NIMH are preserved (1) to one suitable for the nitroimidazole phototriggered release (2) and whose antibacterial activity against B. subtilis, chosen as cellular model, is effectively improved upon light exposure. This study may provide a fundamental knowledge on the use of Ru(II)−polypyridyl complexes to incorporate and/or photorelease biologically relevant nitroimidazole derivatives in the design of a novel class of antimicrobials.
Human ferritin platforms containing Ru(ii)-polypyridyl-based photosensitizers effectively target cancer cells and provide cytotoxic effects upon light-activation.
The synthesis of a new RuII complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2′-bipyridyl unit linked, via methylene bridges in its 4 and 4′ positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2L]2+) is reported. Protonation and ZnII binding by [Ru(phen)2L]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII/RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2L]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2[Ru(phen)2L]BPA(H−2)}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII(phen)2bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.
In photodynamic therapy (PDT), Ru(II) polypyridyl complexes (RPCs) featuring the popular π-expansive benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn) ligand have attracted much attention, mainly due to the good singlet oxygen sensitizing properties imparted by...
Ruthenium(II) polypyridyl complexes (RPCs) are gaining
momentum
in photoactivated chemotherapy (PACT), thanks to the possibility of
overcoming the classical reliance on molecular oxygen of photodynamic
therapy while preserving the selective drug activation by using light.
However, notwithstanding the intriguing perspectives, the translation
of such an approach in the development of new antimicrobials has been
only barely considered. Herein, MTZH-1 and MTZH-2, two novel analogues
of metronidazole (MTZ), a mainstay drug in the treatment of anaerobic
bacterial infections, were designed and inserted in the strained ruthenium
complexes [Ru(tpy)(dmp)(MTZ-1)]PF6 (Ru2) and
[Ru(tpy)(dmp)(MTZ-2)]PF6 (Ru3) (tpy = terpyridine,
dmp = 2,9-dimethyl-1,10-phenanthroline) (Chart 1). Analogously to
the parental compound [Ru(tpy)(dmp)(5NIM)]PF6 (Ru1) (5-nitroimidazolate), the Ru(II)-imidazolate coordination of MTZ
derivatives resulted in promising Ru(II) photocages, capable to easily
unleash the bioactive ligands upon light irradiation and increase
the antibacterial activity against Bacillus subtilis, which was chosen as a model of Gram-positive bacteria. The photoreleased
5-nitroimidazole-based ligands led to remarkable phototoxicities under
hypoxic conditions (<1% O2), with the lead compound Ru3 that exhibited the highest potency across the series,
being comparable to the one of the clinical drug MTZ. Besides, the
chemical architectures of MTZ derivatives made their interaction with
NimAunfavorable, being NimA a model of reductases responsible for
bacterial resistance against 5-nitroimidazole-based antibiotics, thus
hinting at their possible use to combat antimicrobial resistance.
This work may therefore provide fundamental knowledge in the design
of novel photoresponsive tools to be used in the fight against infectious
diseases. For the first time, the effectiveness of the “photorelease antimicrobial therapy” under therapeutically
relevant hypoxic conditions was demonstrated.
Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the ball milling approach. The ball milling formation of boron esters between PBA BODIPY and dextran proved to be more efficient in terms of reaction time, amount of reactants, and labelling degree compared to the corresponding solution-based synthetic route. PBA-BODIPY dextran assembles into nanoparticles of around 200 nm by hydrophobic interactions. The resulting PBA-BODIPY dextran nanoparticles retain an apolar interior as proved by pyrene fluorescence, suitable for the encapsulation of hydrophobic drugs with high biocompatibility while remaining fluorescent.
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