Chemical data as markers of the geographical origins of sugarcane spirits.

In an attempt to classify sugarcane spirits according to their geographic region of origin, chemical data for 24 analytes were evaluated in 50 cachaças produced using a similar procedure in selected regions of Brazil: São Paulo - SP (15), Minas Gerais - MG (11), Rio de Janeiro - RJ (11), Paraiba -PB (9), and Ceará - CE (4). Multivariate analysis was applied to the analytical results, and the predictive abilities of different classification methods were evaluated. Principal component analysis identified five groups, and chemical similarities were observed between MG and SP samples and between RJ and PB samples. CE samples presented a distinct chemical profile. Among the samples, partial linear square discriminant analysis (PLS-DA) classified 50.2% of the samples correctly, K-nearest neighbor (KNN) 86%, and soft independent modeling of class analogy (SIMCA) 56.2%. Therefore, in this proof of concept demonstration, the proposed approach based on chemical data satisfactorily predicted the cachaças' geographic origins.

Chemical Typification of the Sugarcane Spirits Produced in São Paulo State.

UNLABELLED: To typify São Paulo State sugarcane spirits, 37 chemical compounds were analyzed in 81 Brazilian sugarcane spirits (cachaça), which were produced in different cities from São Paulo State. Among these samples, 56 were distilled in copper alembics, and the other 25 were distilled in steel columns. Hierarchical cluster analysis and principal component analysis were performed with both chemical data sets. The chemical profiles of the cachaças distilled in the column apparatus formed 4 specific clusters, which correspond to 4 distinct geographic regions of São Paulo State. For the cachaças that were distilled in copper alembics, 2 cachaça clusters were formed; however, no correlation between their respective chemical similarities and geographical origins was observed. PRACTICAL APPLICATION: This study aims to differentiate the many sugarcane spirits that are produced throughout Brazil's São Paulo State using chemical analysis with chemometric tools. This contribution is expected to improve the production process of cachaças, map the regions that produce the best cachaças, and assure consumers about a product's provenance.

Tailoring NO donors metallopharmaceuticals: ruthenium nitrosyl ammines and aliphatic tetraazamacrocycles.

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.

Functionalization of PAMAM dendrimers with [Ru(III)(edta)(H2O)](-).

The anchoring of K[Ru(III)(edta)(Cl)] on poly(amidoamine) dendrimers (PAMAM of three generations G(x)/Ru (x=0, 2 and 3)) through a peptide type bond yielded the aquo species, [Ru(III)(edta)(H2O)] on dendrimer surface, and upon NO exposure, yielded their nitrosyl analogues, G(x)/RuNO. Characterization of these compounds by elemental analysis, and a UV-vis, IR and 13C NMR spectroscopies indicated the immobilization of 4, 12 and 29 molecules of [Ru(III)(edta)(H2O)] or of the nitrosyl complex [Ru(II)(edta)NO] on the dendrimer surface for G(X)=0, 2 and 3, respectively. For each complex the electrochemical spectrum presented only one redox process with redox potential values of -0.20 and -0.32 V(vs SCE) attributed to the Ru(III)/Ru(II) and NO+/NO(0) couples in G(x)/Ru and G(x)/RuNO, respectively. The one-electron reduction of G(x)/RuNO+ generates G(x)/RuNO(0), which undergoes aquation with a k(-NO) of 2.1+/-0.7 x 10(-3)s(-1) (pH 1.0, mu=0.2 mol/L, CF3COOH/NaCF3COO, 25 degrees C). The G(x)/RuNO species induced a relaxing effect in aortic rings denuded of endothelium and exhibited in vitro assay trypanocidal activity.

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

BACKGROUND AND PURPOSE: 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 Trypanosoma cruzi, the agent responsible for the American trypanosomiasis (Chagas' disease). EXPERIMENTAL APPROACH: Ruthenium NO donors were incubated with a partially drug-resistant strain of T. cruzi and the anti-proliferative and trypanocidal activities evaluated. In a mouse model of acute Chagas' disease, trypanocidal activity was evaluated by measuring parasitemia, survival rate of infected mice and elimination of amastigotes in myocardial tissue. KEY RESULTS: In vitro, the observed anti-proliferative and trypanocidal activities of trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) were due to NO liberated upon reduction of these nitrosyls. Ru(NO)isn had a lower IC(50 epi) (67 microM) than the NO donor, sodium nitroprusside (IC(50 epi)=244 microM) and Ru(NO)imN (IC(50 try)=52 microM) was more potent than gentian violet (IC(50 try)=536 microM), currently used in the treatment of blood. Both ruthenium nitrosyls eliminated, in vivo, extracellular as well as intracellular forms of T. cruzi in the bloodstream and myocardial tissue and allowed survival of up to 80% of infected mice at a dose (100 nmol kg(-1) day(-1)) much lower than the optimal dose for benznidazole (385 micromol kg(-1) day(-1)). CONCLUSIONS AND IMPLICATIONS: Our data strongly suggest that NO liberated is responsible for the anti-proliferative and trypanocidal activities of the ruthenium NO donors and that these compounds are promising leads for novel and effective anti-parasitic drugs.

The effects of ruthenium tetraammine compounds on vascular smooth muscle.

The time course of the relaxation effect induced by a single dose (3 x 10(-6) mol/L) of trans-[Ru(NH3)4L(NO)]3+ (L=nic, 4-pic, py, imN, P(OEt)3, SO(3)(2-), NH3, and pz) species and sodium nitroprusside (4 x 10(-9) mol/L) was studied in aortic rings without endothelium and pre-contracted with noradrenaline (1 x 10(-6) mol/L). All the compounds induced a relaxing effect in the aortic rings, but the intensity and time of relaxation were different. Only the species where L=py, 4-pic, and P(OEt)3 were able to induce 100% (99-100%) of the relaxing effect during the assay. trans-[Ru(NH3)4(L)(NO)]3+ (L=SO(3)(2-) and NH3) showed the lowest relaxing effect (36 and 37%, respectively) when compared with the other compounds. Relationship was observed between the time corresponding to half of the maximum relaxation intensity observed and, respectively, k-NO, E0'[Ru(NO)]3+/[Ru(NO)]2+ in trans-[Ru(NH3)4(L)(NO)]3+ species and E0'Ru(III)/Ru(II) in trans-[Ru(NH3)4(L)(H2O)]3+ ions. These relationships strongly suggested that the NO liberation from the reduced nitrosyl complexes was responsible for the observed relaxation.

Copper(II) catalysis in cyanide conversion into ethyl carbamate in spirits and relevant reactions.

The role of copper(II) species in the oxidation of inorganic cyanide to cyanate and in the conversion of cyanate or urea into ethyl carbamate was investigated. The oxidation process has been shown to be independent from the dissolved oxygen. Elemental analysis and infrared spectroscopy have shown the formation of a mixed copper carbonate/hydroxide in the process of oxidation of cyanide to cyanate in water/ethanol. The complexation to Cu(II) of cyanate formed upon cyanide oxidation makes the former more susceptible to nucleophilic attack from ethanol, with conversion into ethyl carbamate. Comparatively, urea has a minor role with respect to cyanide in the formation of ethyl carbamate. Therefore, the urea present in some samples of Brazilian sugar cane spirit (cachaça) has been shown to have almost no influence on the ethyl carbamate content of cachaças, which comes essentially from cyanide. Fe(II,III) affords results similar to those found with Cu(II). Some suggestions are presented to avoid ethyl carbamate formation in spirits during distillation.

The influence of NO-containing ruthenium complexes on mouse hippocampal evoked potentials in vitro.

The influence of different, nitric oxide-containing ruthenium complexes on the evoked potentials recorded from the CA1 region of the mouse hippocampus in vitro has been investigated. Of the compounds tested, only trans-[(NO)(P(OEt)3)(NH3)4Ru](PF6)3 (1-2.5 mM) exerted a strong facilitatory action on the population spike, the EPSP, and the spontaneous activity. Its activity probably depends upon its ability to release NO following reduction. The phosphito ligand is important both in terms of adjusting the reduction potential of the complex to be biologically accessible and in labilizing the coordinated NO. The effects of this compound could not be reversed by perfusion. Scavenging NO in slices preincubated with oxyhemoglobin prior to the addition of this compound eliminated its neurophysiological effects. The control molecules trans-[(P(OEt)3)2(NH3)4Ru](PF6)2, trans-[(H2O)(P(OEt)3) (NH3)4Ru](PF6)3, and [(NO)(NH3)5Ru]Cl3, which are structurally similar, but unable to generate NO, were ineffective. NaNO2 suppressed neuronal firing. Attempts to induce Long-Term Potentiation (LTP) at the time of maximal effect of trans-[(NO)(P(OEt)3)(NH3)4Ru](PF6)3 were unsuccessful, suggesting that the mechanism of amplification induced by trans-[(NO)(P(OEt)3)(NH3)4Ru](PF6)3 and LTP may share common pathways.

Detection of the EPR spectra of NO. in ruthenium(II) complexes.

The EPR of NO. can be detected in the liquid and solid states when crystal fields are sufficient to remove the axial symmetry and separate the (pi*)x and (pi*)y orbitals by a few hundred reciprocal centimeters. The theory of the EPR spin Hamiltonian of bound NO. is reviewed, further developed, and then applied to the observed frozen-liquid spectra of NO. bound to Ru(II) obtained from RuIINO+ complexes by reduction. Comparisons to earlier reports on the observation of the EPR spectra of NO. are made.

A controlled NO-releasing compound: synthesis, molecular structure, spectroscopy, electrochemistry, and chemical reactivity of R,R,S,S-trans-[RuCl(NO)(cyclam)]2+(1,4,8,11-tetraazacyclotetradecane).

The synthesis of trans-[RuCl(NO)(cyclam)]2+ (cyclam = 1,4,8,11-tetraazacyclotetradecane) can be accomplished by either the addition of cyclam to K2[RuCl5NO] or by the addition of NO to trans-[RuCl(CF3SO3)(cyclam)](CF3-SO3). Crystals of trans-[RuCl(NO)(cyclam)](ClO4)2 form in the monoclinic space group P2(1)/c, with unit cell parameters of a = 7.66500(2) A, b = 24.7244(1) A, c = 16.2871(2) A, beta = 95.2550(10) degrees, and Z = 4. One of the two independent molecules in the unit cell lies disordered on a center of symmetry. For the ion in the general position, the Ru-N and N-O bond distances and the [Ru-N-O]3+ bond angle are 1.747(4) A, 1.128(5) A, 178.0(4) degrees, respectively. In both ions, cyclam adopts the (R,R,S,S) configuration, which is also consistent with 2D COSY 1H NMR studies in aqueous solution. Reduction (E degree = -0.1 V) results in the rapid loss of Cl- by first-order kinetics with k = 1.5 s-1 and the slower loss of NO (k = 6.10 x 10(-4) s-1, delta H++ = 15.3 kcal mol-1, delta S++ = -21.8 cal mol-1 K-1). The slow release of NO following reduction causes trans-[RuCl(NO)(cyclam)]2+ to be a promising controlled-release NO prodrug for vasodilation and other purposes. Unlike the related complex trans-[Ru(NO)(NH3)4(P(OEt)3)](PF6)2, trans-[RuCl(NO)(cyclam)]Cl2 is inactive in modulating evoked potentials recorded from mice hippocampal slices probably because of the slower dissociation of NO following reduction.

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.

Evidence of competitive mechanisms during oxidation of CS(2)N(-)(3) by permanganate ion in alkaline solution.

The oxidation of the 1,2,3,4-thiatriazole-5-thiolate ion, CS(2)N(-)(3), by permanganate ions in alkaline medium has been investigated over a wide range of oxidant concentrations. With a moderate excess of permanganate ion a 17-electron reaction takes place, yielding sulphate, nitrogen and carbon dioxide. With a high permanganate concentration the pseudohalide undergoes a 26-electron reaction yielding sulphate, carbon dioxide and nitrite as final products. These two different stoichiometries arise from the existence of competitive mechanisms and the ratio C(MnO(-)(4))/C(CS(2)N(-)(3)) will determine the course of the reaction.

Spectrophotometric determination of the pseudohalide 1,2,3,4-thiatriazol-5-thiolate ion, CS(2)N(-)(3).

A critical study of the analytical methods available for the CS(2)N(-)(3) ion is reported. A modification of the argentimetric method is proposed. An oxidative study gave evidence of various steps corresponding to incompletely oxidized intermediates. The absorption maximum of the 1,2,3,4-thiatriazol-5-thiolate ion at 313 nm, with molar absorptivity of 7.4 x 10(-3)1.mole(-1).cm(-1) is utilized to develop a new analytical method. The spectrophotometric procedure is rapid and free from interference by many ions. A value of 1.51 +/- 0.02 was found for pK of HCS(2)N(3) at an ionic strength of 1.00M and at 25 degrees . The spectrum of CS(2)N(-)(3) is changed by increasing acidity of the medium, due to the formation of HCS(2)N(3); an isosbestic point is observed at 251 nm.