Tailoring NO Donors Metallopharmaceuticals: Ruthenium Nitrosyl Ammines and Aliphatic Tetraazamacrocycles
Abstract:The discovery of the involvement of nitric oxide (NO) in several physiological and pathophysiological processes launched a spectacular increase in studies in areas such as chemistry, biochemistry, and pharmacology. As a consequence, the development of NO donors or scavengers for regulation of its concentration and bioavailability in vivo is required. In this sense, ruthenium nitrosyl ammines and aliphatic tetraazamacrocyles have attracted a lot of attention due to their unique chemical properties. These complexes are water soluble and stable in solution, not to mention that they can deliver NO when photochemically or chemically activated by the reduction of the coordinated nitrosonium (NO+). The tuning of the energies of the charge transfer bands, the redox potential, and the specific rate constants of NO liberation, in both solution and matrices, is desirable for the achievement of selective NO delivery to biological targets, hence making the ruthenium ammines and aliphatic tetraazamacrocyles a quite versatile platform for biological application purposes. These ruthenium nitrosyls have shown to be active in firing neurons in mouse hippocampus, performing redox reactions in mitochondria, acting in blood pressure control, exhibiting cytotoxic activities against trypanosomatids (T.cruzi and L.major) and tumor cells. This tailoring approach is explored here, being heavily supported by the accumulated knowledge on the chemistry and photochemistry of ruthenium complexes, which allows NO donors/scavengers systems to be custom made designed.
Keywords: = quantum yield of release of NO; Antiparasitic Effects; Bioavailability; Biodistribution; HepG2 cells; Hipotensive Properties; Mouse Hippocampus; N-hydroxyguanidines; NRU = neutral red uptake; P(OEt)3 = triethylphosphite; PAMAM = polyamidoamine dendrimers; RCR = respiratory control ratio; Ruthenium; T. cruzi = Trypanosoma cruzi; TI = therapeutic; Toxicity; ali-phatic tetraazamacrocyles; aliphatic tetraazamacrocyles; biological applications; differential pulse polarography (DPP); iron-cluster-containing; mac = macrocyclic ligand; mitochondrial permeability transition (MPT); neurotransmission; nic = nicotinamide; nitric oxide carriers; nitric oxide synthase enzyme (NOS); nitrosyls; pathogens killing; performing redox reactions; photodynamic therapy (PDT); pseudo-octahedral complexes; ruthenium nitrosyl ammines; trypanosomatids
Document Type: Research Article
Publication date: November 1, 2010
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