Ruthenium Complexes as NO Donors for Vascular Relaxation Induction

Abstract

Nitric oxide (NO) donors are substances that can release NO. Vascular relaxation induction is among the several functions of NO, and the administration of NO donors is a pharmacological alternative to treat hypertension. This review will focus on the physicochemical description of ruthenium-derived NO donor complexes that release NO via reduction and light stimulation. In particular, we will discuss the complexes synthesized by our research group over the last ten years, and we will focus on the vasodilation and arterial pressure control elicited by these complexes. Soluble guanylyl cyclase (sGC) and potassium channels are the main targets of the NO species released from the inorganic compounds. We will consider the importance of the chemical structure of the ruthenium complexes and their vascular effects.

Design, Reactivity, and Biological Activity of Ruthenium Nitrosyl Complexes

“…The nitrosyl ruthenium complexes slowly induce relaxation that is at least 10 Â more potent than that promoted by SNP, a standard drug ( (32) is enough to activate the biological pathway, and the process takes less time than those conducted in the dark. For the cis-[Ru II (NO + )(bpy) 2 (py) Cl] 2+ complex, the maximum effect is 100%, but this effect does not occur in the absence of light (46).…”

“…The relaxation induced by ruthenium compounds involves activation of cyclic guanosine 3 0 ,5 0 -monophosphate (cGMP), which could mediate several biological mechanisms. As described in our work (27,32,39,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51) one of these mechanisms involves activation of a calcium-sensitive potassium channel through the cGMP-dependent protein kinase. Another common process is induction of cell membrane hyperpolarization.…”

The versatile ruthenium(II/III) tetraazamacrocycle complexes and their nitrosyl derivatives

“…NO release from this complex was also found to occur via photo induced electron transfer from [Ru(pyz)(NH 3 ) 5 ] 2+ ( irr = 436 nm) in phosphate buffer solution in a concentration dependent manner [190]. Interestingly, phosphate anions appear to mediate trans-[Ru II (NO + )Cl([15]aneN 4 )] 2+ reduction and, therefore, NO generation [51,191], meaning that this must be taken into consideration when performing an experiment in phosphate buffer.…”

“…NO release upon irradiation can potentially be used as a biological tool and in clinical applications [40,41,49,51,52]. The photoinduced release of NO from ruthenium nitrosyl complexes is a strategy that offers the advantages of not just only a single by-product (the ruthenium photoproduct) along with chloride for tetraazamacrocyclic complexes in some cases, but also and importantly site-specific delivery of the reactive species NO to cells, thereby controlling location, timing, and dosage.…”

“…with low toxicity for healthy cells. Both the chemical properties and biological activities of ruthenium nitrosyl complexes have been extensively investigated [40,[48][49][50][51], not only in solution but also incorporated into drug delivery systems such as polymeric nanoparticles [52][53][54]. With that aim, a large number of ruthenium nitrosyl complexes with macrocyclic ligands ([Ru(NO)L(mac)] q+ ) have been reported [40,47,48,50].…”