Review Biological activity of ruthenium nitrosyl complexes Elia Tfouni b , Daniela Ramos Truzzi a , Aline Tavares a , Anderson Jesus Gomes c , Leonardo Elias Figueiredo b , Douglas Wagner Franco a,⇑ a Departamento de Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil b Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil c Faculdade de Ceilândia, Universidade de Brasília, Brasília, DF, Brazil article info Article history: Received 2 September 2011 Revised 29 November 2011 Available online 7 December 2011 Keywords: Ruthenium nitrosyls Nitric oxide carriers Reactivity and biologic activity abstract Nitric oxide plays an important role in various biological processes, such as neurotransmission, blood pressure control, immunological responses, and antioxidant action. The control of its local concentration, which is crucial for obtaining the desired effect, can be achieved with exogenous NO-carriers. Coordina- tion compounds, in particular ruthenium(III) and (II) amines, are good NO-captors and -deliverers. The chemical and photochemical properties of several ruthenium amine complexes as NO-carriers in vitro and in vivo have been reviewed. These nitrosyl complexes can stimulate mice hippocampus slices, pro- mote the lowering of blood pressure in several in vitro and in vivo models, and control Trypanosoma cruzi and Leishmania major infections, and they are also effective against tumor cells in different models of can- cer. These complexes can be activated chemically or photochemically, and the observed biological effects can be attributed to the presence of NO in the compound. Their efficiencies are explained on the basis of the [Ru II NO + ] 3+ /[Ru II NO 0 ] 2+ reduction potential, the specific rate constant for NO liberation from the [RuNO] 2+ moiety, and the quantum yield of NO release. Ó 2011 Published by Elsevier Inc. Contents Introduction............................................................................................................ 38 Nitric oxide activation on ruthenium(II) nitrosyl complexes ..................................................................... 41 Biological molecules and nitric oxide activation on ruthenium(II) nitrosyl complexes ............................................ 41 Photochemical activation ............................................................................................. 41 Biological tests.......................................................................................................... 42 Vasodilation and vasoconstriction ...................................................................................... 42 Ruthenium nitrosyls as anti-infective agents ............................................................................. 44 Cancer ............................................................................................................ 46 Immobilization of ruthenium nitrosyl complexes .......................................................................... 48 Conclusions and perspectives .............................................................................................. 48 References ........................................................................................................... 49 Introduction Coordination compounds have long been used as metallophar- maceuticals [1–3]. There is a wide range of metal complexes that have biological activities and applications for diseases, such as can- cer [4–6], cardiovascular problems [7], arthritis [8], and parasitosis [9], and some of these complexes are commercially available. The best known and most studied metal drugs are the anticancer com- pounds of platinum, which have been used since the antitumor activity of cisplatin (cis-diamminedichloridoplatinum(II), [cis- Pt II (NH 3 ) 2 Cl 2 ]) was discovered in the 1960s [3]. The continued development of metal complexes has sought to overcome the drug resistance and side effects of [cis-Pt II (NH 3 ) 2 Cl 2 ]. Iron complexes have been extensively used in the treatment of anemia, cancer, and cardiovascular problems. Iron(II) citrate is a classical anemia treatment [10]; ferrocenyl derivatives are antican- cer drugs for breast cancer [11], while sodium nitroprusside (SNP) 1089-8603/$ - see front matter Ó 2011 Published by Elsevier Inc. doi:10.1016/j.niox.2011.11.005 ⇑ Corresponding author. Fax: +55 16 3373 9976. E-mail address: douglas@iqsc.usp.br (D.W. Franco). Nitric Oxide 26 (2012) 38–53 Contents lists available at SciVerse ScienceDirect Nitric Oxide journal homepage: www.elsevier.com/locate/yniox