Douglas W. Franco

Structure, chemical and photochemical reactivity and biological activity of some ruthenium amine nitrosyl complexes

Abstract Through spectroscopic (X-ray, Infrared, 1H-NMR, EPR, UV–vis) and electrochemical (cyclic voltammetry, differential pulse polarography) data and quantum mechanical calculations, the formulation [Ru(II)NO+] was attributed to a series of new ruthenium(II) amine compounds. A remarkable stability of the Ru(II) relative to Ru(III) was observed upon coordination to NO. The presence of nitrosyl in the coordination sphere results in dramatic implications in the lability, acidity and redox properties of the ligand trans to NO. These effects are higher than expected just on the basis of one unity increment in the metal center charge. Based on molecular orbital (MO) analysis and on reduction product analysis, the site of the reduction [Ru(NO)]3++e−→[Ru(NO)]2+ was assigned to the NO ligand. The dissociation of the coordinated NO0 is dependent on the trans effect and trans influence of the trans ligand L. Irradiation of the nitrosyl complexes with 300–350 nm light results in NO aquation and formation of the corresponding aquaruthenium(III) complex, i.e. trans-[ Ru ( NO )( NH 3 ) 4 L ] 3+ → H 2 O , H + hν trans-[ Ru ( NH 3 ) 4 ( H 2 O ) L ] 3+ + NO 0 Irradiation in the visible region (400–500 nm) did not result in any observable reaction in solution; however, at low temperature and in the solid state, evidence in favor of the formation of linkage isomers has been obtained. The hypotensive properties of trans-[Ru(NO)(NH3)4(P(OC2H5)3)](PF6)3 and trans-[Ru(NO)Cl(cyclam)](ClO4)2 have been demonstrated in mice and rats.

Biological activity of ruthenium nitrosyl complexes.

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. Coordination 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, promote 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 cancer. 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.

Efficient and clean synthesis of N-alkyl carbamates by transcarboxylation and O-alkylation coupled reactions using a DBU-CO2 zwitterionic carbamic complex in aprotic polar media

N-Alkyl carbamates were obtained with good to excellent yields by clean and mild transcarboxylation of several amines with the previously synthesized DBU–CO2 complex and subsequent O-alkylation. Transcarboxylation was found to be selective, as only carbamate was formed from 1-hydroxy-2-aminobutanol.

Qualitative and quantitative high-performance liquid chromatographic analysis of aldehydes in Brazilian sugar cane spirits and other distilled alcoholic beverages

A study is presented on the high-performance liquid chromatographic analysis of eighteen aldehydes in Brazilian sugar cane spirits and other international brandies. The aldehydes were separated by reversed-phase high-performance liquid chromatography as 2,4-dinitrophenylhydrazones (DNPHs). A very good chromatographic separation was achieved for eighteen different aldehyde-DNPHs. The proposed methodology is quite simple and not very time-consuming. Ten aldehydes were identified in 75 beverages and quantified using the external standard method with UV detection at 365 nm. A detailed knowledge of the aldehyde content should significantly contribute to improving the quality control of distilled spirits.

Electronic spectra of trans-[Ru(NH3)4(L)NO]3+/2+ complexes

Density functional theory (DFT) with local, non-local and hybrid functionals has been used to obtain the geometry of a series of nitrosyl–metal complexes [Ru(NH3)4(L)NO]n+, where L=NH3, H2O, pyrazine and pyridine (n=3), Cl− and OH− (n=2). Based on the molecular orbital analysis and the time dependent DFT (TD-DFT) calculations, we discuss the electronic structure and the assignment of the bands in the electronic spectra of these complexes.

In vitro and in vivo antiproliferative and trypanocidal activities of ruthenium NO donors

Many compounds liberating NO (NO donors) have been used as therapeutic agents. Here we test two ruthenium nitrosyls, which release NO when activated by biological reducing agents, for their effects in vitro and in vivo against Trypanasoma cruzi, the agent responsible for the American trypanosomiasis (Chagas’ disease).

Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro/in vivo trypanocidal activity

Background and purpose:  The discovery of the pharmacological functions of nitric oxide has led to the development of NO donor compounds as therapeutic agents. A new generation of ruthenium NO donors, cis‐[Ru(NO)(bpy)2L]Xn, has been developed, and our aim was to show that these complexes are able to lyse Trypanosoma cruzi in vitro and in vivo.

Metastable excited state and electronic structure of [Ru(NH3)5NO]3+ and [Ru(NH3)4(OH)NO]2+

Abstract Light-induced metastable excited states of complexes [Ru(NH3)5NO]3+ and [Ru(NH3)4(OH)NO]2+ were investigated by FTIR spectroscopy. Both systems showed only one metastable excited state (MSI), with decay temperatures higher than 200 K. MSI formation occurs upon irradiation in the visible band (450–500 nm). According to ab initio density functional theory (DFT) molecular orbital analysis and ZINDO semi empirical C.I. calculation, MSI originates from the charge transfer transition 2b2(dxy)→7e(π*NO). Since irradiation in regions other than the charge transfer transition causes fast depopulation of the metastable excited state, this light-induced decay is tentatively assigned to light absorption by the systems in the excited state.

A new inorganic vasodilator, trans-[Ru(NO)(NH3)4(POEt)3](PF6)3: hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models☆

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.

Identification and dosage by HRGC of minor alcohols and esters in Brazilian sugar-cane spirit

A presenca de 51 compostos volateis, entre alcoois e esteres, em aguardentes de cana (cachaca) foi investigada por cromatografia gasosa de alta resolucao. Os seguintes compostos foram identificados e quantificados: metanol, 1,4-butanodiol, alcool 2-feniletilico, alcool amilico, alcool cetilico, alcool cinâmico, n-decanol, geraniol, alcool isoamilico, isobutanol, mentol, n-butanol, n-dodecanol, n-propanol, n-tetradecanol, propionato de amila, acetato de etila, benzoato de etila, heptanoato de etila, valerato de isoamila, propionato de metila, butirato de propila. O teor medio de alcoois superiores (262 mg/ 100 mL de alcool anidro a.a.) e o teor medio de esteres (24 mg/100 mL a.a.) em cachacas sao menores que os encontrados em outros destilados. O teor medio de metanol em cachacas, (6 mg/100 mL a.a.) e o mesmo que o encontrado em rum e menor em relacao ao encontrado em destilados de uva. Com relacao aos compostos analisados, nao foram observadas diferencas significativas no perfil quimico qualitativo das cachacas analisadas.