Katrina M Miranda

Abstract:

Described are the spectra and kinetics of transients formed by laser flash photolysis of the ruthenium nitrosyl nitrito complexes Ru(P)(NO)(ONO), P= TPP (meso-tetraphenylporphyrin), OEP (octaethylporphyrin), TmTP (tetra(m- tolyl)porphyrin); and FTTP (tetra(m-trifluoromethylphenyl)porphyrin)in benzene solutions. Two transient decay processes are seen on the time frame ( 1 ms) of the flash photolysis experiment, and a residual difference spectrum, which decays to baseline on a longer time frame, is noted as well. The accumulated evidence points to the formation of two primary photoproducts, Ru(P)(ONO) (A) formed by NO photolabilization and Ru(P)(NO) (B) formed by NO2 photolabilization. Both decay by NO dependent pathways, the reaction of A with NO to re-form Ru(P)(NO)(ONO) being substantially faster (2.4-5.5 x 10⁸ M^-1 s^-1 in ambient temperature benzene) than the reaction of B with NO (2.4-10 x 10⁷ M^-1 s^-1). The product of the latter reaction is apparently the dinitrosyl complex Ru(P)(NO)2, which undergoes a much slower thermal reaction with excess NO to give again Ru(P)(NO)(ONO). The possibility of B being the oxo complex O=Ru(P)(No) formed by NO loss from coordinated nitrite was considered but concluded to be a minor pathway at best. Isotopic exchange reactions using either labeled complex or labeled NO in cyclohexane demonstrate photochemical exchange of NO into both the nitrosyl and nitrito complexes, and time-resolved infrared experiments are consistent with formation of a long-lived nitrosyl-containing intermediate. Flash photolysis studies of the respective nitrosyl chloro complexes Ru(TPP)(NO)Cl and Ru(OEP)(NO)Cl indicate that only a single transient species, presumably Ru(P)Cl, is formed in each case, and this decays by a single NO dependent pathway back to starting material.

Abstract:

The synthesis, X-ray crystal structures, and some spectroscopic and chemical properties of the nitrosylruthenium(II) porphyrin complexes Ru(TPP) (NO) (ONO), Ru(TPP) (NO) (OH), Ru(OEP) (NO) (ONO), and Ru(OEP) (NO)-(OH) (TPP = tetraphenylporphyrinato dianion; OEP = octaethylporphyrinato dianion) derived from the analogous Ru(II) carbonyl complexes are reported. Also described are experiments which quantitatively demonstrate that N2O is formed as a product of the synthesis scheme and that NO serves as the principal oxidant in the transformation of N(II) to N(III). The two TPP complexes are isostructural and consist of columns of molecules stacked along the c axis. The two OEP complexes are also isostructural and can be considered as layers of OEP complexes stacked along the b axis with solvent molecules situated at the cavities between layers. The nitrite ions are coordinated in a unidentate fashion through the oxygen atom. Crystal data for Ru(TPP) (NO) (ONO) (1): M = 789.79, space group I4/m (No. 87), a = 13.6529(6) Å, c = 9.7904(5) Å, V = 1825.0(2) ų, Z = 2, ρ = 1.437 g cm^-3, purple bipyramid, 2θmax = 50.0°, R(F) = 4.87% for 86 parameters and 838 reflections with I > 2σ(I). Crystal data for Ru(TPP) (NO) (OH) (2): M = 760.79, space group I4/m (No. 87), a = 13.5423(4) Å, c = 9.7150-(4) Å, V= 1781.7(1) ų, Z = 2, ρ = 1 .418 g cm^-3, dark red plate, 2θmax = 50.0°, R(F) = 3.92% for 83 parameters and 811 reflections with I > 2σ(I). Crystal data for Ru(OEP) (NO)(ONO)·CH2Cl2 (3): M = 794.77, space group P21 (No. 4), a = 10.7687(2) Å, b = 21.0320(2) Å, c = 8.5936(2) Å, β= 102.683(1)°, V= 1898.85(6) ų, Z = 2, ρ = 1.390 g cm^-3, black plate, 2θmax = 50.0°, R(F) = 6.23% for 453 parameters and 4702 reflections with I > 2σ(I). Crystal data for Ru(OEP) (NO) (OH)·C2H5OH (4): M = 726.91, space group P21 (No. 4), a = 10.8474-(7) Ǎ, b = 21.002(1) Å, c = 8.3646(5) Å, β= 103.571(1)°, V= 1852.4(2) ų, Z= 2, ρ = 1.303 g cm^-3, brown plate, 2θmax = 45.0°, R(F) = 6.74% for 421 parameters and 3527 reflections with I > 2σ(I).

PMID: 16910783;Abstract:

Nitrite (NO2^-), N^G-hydroxy-L-arginine (NOHA), and hydroxylamine (NH2OH) are products of nitric oxide synthase (NOS) activity and can also be formed by secondary reactions of nitric oxide (NO). These compounds are commonly considered to be rather stable and as such to be dosimeters of NO biosynthesis. However, each can be converted via metal-catalyzed reactions into either NO or other reactive nitrogen oxide species (RNOS), such as nitrogen dioxide (NO2) and nitroxyl (HNO), which have biologic activities distinct from those of the parent molecules. Consequently, certain aspects of tissue regulation controlled by RNOS may be dictated to a significant extent by metal-dependent reactions, thereby offering unique advantages for cellular and tissue regulation. For instance, because many metal-catalyzed reactions depend on the redox and oxygen status of the cellular environment, such reactions could serve as redox indicators. Formation of RNOS by metal-mediated pathways would confine the chemistry of these species to specific cellular sites. Additionally, such mechanisms would be independent both of NO and NOS, thus increasing the lifetime of RNOS that react with NO. Thus metal-mediated conversion of nitrite, NOHA, and NH2OH into biologically active agents may provide a unique signaling mechanism. In this review, we discuss the biochemistry of such reactions in the context of their pharmacologic and biologic implications. © Mary Ann Liebert, Inc.

Abstract:

The function of nitric oxide (^•NO) in pathophysiology remains confounding as both protective and cytotoxic effects of ^•NO have been demonstrated in many disease processes. Nitric oxide chemistry culminating in the generation of oxidative as well as nitrosative intermediates have generally been proposed as mediators of pathophysiology and have overshadowed the antioxidant capabilities of ^•NO. However, the counteracting role of ^•NO in providing a balance under conditions of oxidative and nitrosative stress has been underappreciated. The purpose of this review is the discussion of the role of ^•NO as an antioxidant and interceptor of more potent reactive intermediates in normal physiology and disease. © 2004 Bentham Science Publishers Ltd.

PMID: 14642390;Abstract:

The poly(ADP-ribose) polymerase (PARP) family of nuclear enzymes is involved in the detection and signaling of single strand breaks induced either directly by ionizing radiation or indirectly by the sequential action of various DNA repair proteins. Therefore, PARP plays an important role in maintaining genome stability. Because PARP proteins contain two zinc finger motifs, these enzymes can be targets for reactive nitrogen oxide intermediates (RNOS) generated as a result of nitric oxide (NO) biosynthesis in an aerobic environment. The effects of RNOS on the activity of purified PARP were examined using donor compounds. Both NO and nitroxyl (HNO) donors were found to be inhibitory in a similar time and concentration manner, indicating that PARP activity can be modified under both nitrosative and oxidative conditions. Moreover, these RNOS donors elicited comparable PARP inhibition in Sf21 insect cell extract and intact human MCF-7 cancer cells. The concentrations of donor required for 90% inhibition of PARP activity produce RNOS at a similar magnitude to those generated in the cellular microenvironment of activated leukocytes, suggesting that cellular scavenging of RNOS may not be protective against PARP modification and that inhibition of PARP may be significant under inflammatory conditions. © 2003 Elsevier Inc.