No abstract

Despite four additional electron‐withdrawing substituents, the octahalogenated porphyrins 2 are more easily oxidized than their tetra‐halogenated counterparts 1. This apparent paradox can be explained by the structures of the molecules: porphyrins 2 are almost planar, whereas in 1 steric interactions are minimized by a saddle conformation, which makes these porphyrins easier to oxidize.

The X-ray structures of the 8-substituted-pyrrole tetraarylporphyrin 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetramesitylporphyrin (H2TMOBP), its nickel(I1) complex (NiTMOBP), and the nickel(I1) derivative of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20tetrakis(pentafluoropheny1)porphyrin (NiTPFPOBP.1/2CH2C1z) are reported. The synthesis of the free base H,TPFPOBP is also described. All these molecules are nonplanar, displaying saddle-shaped conformations. The saddle distortions minimize the intramolecular steric interactions between the bromine substituents and the ortho (ortho') carbon atoms or ortho (ortho') substituents of the phenyl rings, and consequently, the corresponding contact distances have similar values in all compounds. Because of the distortion of the porphyrin cores, the cavity defined by the ortho (ortho') substituents gives slightly less steric protection than in the nonbrominated nearly planar ortho-and ortho'-substituted tetraarylporphyrin complexes. Crystallographic data: C56H4sN4Brs (H2TMOBP), tetragonal, space group P42,c, a = b = 15.085 (4) A, c = 14.056 (4) A, V = 3198.8 A', Z = 2, RF = 0.054, RwF = 0.069 based on 638 reflections with I > 3a(10), T = 298 K; NiC56H44N4Brs,1s (NiTMOBP), tetragonal, space group P421c, a = b = 15.024 (3) A, c = 14.068 (6) 1, V = 3175.2 A', Z = 2, RF = 0.049, R w F = 0.057 based on 877 reflections with lo > 2.5u(10), T = 298 K; NiCMN4F2 BrsJ/2CH2C12 (NiTPFPOBP-1/2CH2C1z), monoclinic, space group C2/c, a = 18.105 (3) A, b = 22.141 (5) A, c = 24.301 ( 5 ) 1, B = 93.32 (2)O, V = 9725.5 A', Z = 8, RF = 0.047, RwF = 0.064 based on 2896 reflections with Io > 3a(10), T = 298 K.

The tetraaza macrocycles 2-oxa-3-oxotetramesitylporphine (|H(2) 1|) and 2-oxa-3-oxotetrakis(2,6-dichlorophenyl)porphine (|H(2) 2|) and the corresponding iron complexes (|Fe(III)(X) 1| and |Fe(III)(X) 2|; X= Cl(-), OH(-), or SO(3)CF(3)(-)) have been synthesized. These macrocycles are derived from porphyrins by transformation of one pyrrole ring to an oxazolone ring. The resulting lactone functionality serves to restrict but not completely block pi-conjugation around the periphery. These complexes thus share properties with both porphyrins and chlorins. The ferric and high-valent iron complexes have been characterized by a variety of spectroscopic techniques. The molecular structure of |Fe(III)(Cl) 2| has been obtained by X-ray crystallography and shows that the structural changes at the macrocycle periphery do not perturb the coordination sphere of iron relative to the corresponding porphyrin complexes. This is illustrated by the observation that Fe-O frequencies in the resonance Raman spectra of the porpholactone analogues of compounds I and II are not substantially different from those of porphyrins and by the axial appearance of the EPR signals of the high-spin ferric complexes. This is consistent with reports that the Fe=O unit of oxidized porphyrins and chlorins is relatively insensitive to alteration of macrocycle symmetry. Nevertheless, probes of properties of the porpholactone macrocycle ((1)H NMR, resonance Raman skeletal modes) show effects of the asymmetry induced by the oxazolone ring. On the basis of (1)H NMR, EPR, Mössbauer, and resonance Raman data, the singly occupied molecular orbital of oxoferryl porpholactone pi-cation radicals correlates with the a(1u) molecular orbital of porphyrins under D(4)(h)() symmetry. Moreover, the paramagnetic properties and the intramolecular exchange interaction of ferryl iron and the porpholactone pi-radical have been characterized by EPR and magnetic Mössbauer measurements and spin-Hamiltonian analyses. The values J(0) = 17 cm(-)(1) and J(0) = 11 cm(-)(1) obtained for the exchange coupling constants of the oxoferryl porpholactone pi-cation radical complexes |Fe(IV)=O 1|(+) and |Fe(IV)=O 2|(+), respectively, are among the lowest found for synthetic compound I analogues.

experiments we report here, we have measured spectral changes associated with both the disulfide radical anion and the a subunit heme group. Moreover, since we have found that C02*~r educes the heme group in Fe(III)-a-Hb with no attached disulfide and predominantly the disulfide of Fe(III)-a-Hb-SSR, unwanted side reactions due to "contaminating" radical reduction at other protein sites most presumably do not occur in this system.

The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-Ih) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-CPBA and DMDO as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT)·(AACAA)] with DMDO. 2-Ih has not been reported as an oxidative lesion at the level of single/double-stranded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification suggesting that 2-Ih may be a stable biomarker in vivo. The oxidation products have been structurally characterized and the reaction mechanism probed by oxidation of the monomeric species dGuo, dGMP and dGTP. DMDO selectively oxidizes the guanine moiety of dGuo, dGMP and dGTP to 2-Ih, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer through rotation about the formamido C-N bond. Labeling studies with 18O2-m-CPBA and H218O to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-Ih base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker.

Abstract1,3-Butadiene is an important industrial chemical used in the production of synthetic rubber and is also found in gasoline and combustion products. It is a multispecies, multisite carcinogen in rodents, with mice being the most sensitive species. 1,3-Butadiene is metabolized to several epoxides that form DNA and protein adducts. Previous analysis of 1,2,3-trihydroxybutyl-valine globin adducts suggested that most adducts resulted from 3-butene-1,2-diol metabolism to 3,4-epoxy-1,2-butanediol, rather than from 1,2;3,4-diepoxybutane. To specifically examine metabolism of 1,3-butadiene to 1,2;3,4-diepoxybutane, the formation of the 1,2;3,4-diepoxybutane-specific adduct N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was evaluated in mice treated with 3, 62.5, or 1250 ppm 1,3-butadiene for 10 days and rats exposed to 3 or 62.5 ppm 1,3-butadiene for 10 days, or to 1000 ppm 1,3-butadiene for 90 days, using a newly developed immunoaffinity liquid chromatography tandem mass spectrometry assay. In addition, 2-hydroxy-3-butenyl-valine and 1,2,3-trihydroxybutylvaline adducts were determined. The analyses of several adducts derived from 1,3-butadiene metabolites provided new insight into species and exposure differences in 1,3-butadiene metabolism. Mice formed much higher amounts of N,N-(2,3-dihydroxy-1,4-butadiyl)-valine than rats. The formation of 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was similar in mice exposed to 3 or 62.5 ppm 1,3-butadiene, whereas 2-hydroxy-3-butenyl-valine was 3-fold higher at 1250 ppm. In both species, 1,2,3-trihydroxybutyl-valine adducts were much higher than 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine. Together, these data show that 1,3-butadiene is primarily metabolized via the 3-butene-1,2-diol pathway, but that mice are much more efficient at forming 1,2;3,4-diepoxybutane than rats, particularly at low exposures. This assay should also be readily adaptable to molecular epidemiology studies on 1,3-butadiene-exposed workers

The perchloratoiron(III) complexes of a series of 2,6-disubstituted tetraphenylporphyrin ligands, where the 2,6-phenyl substituents were -H, -F, -Cl, -Br, or -OMe, as well as two 2,4,6-phenyl-substituted complexes, where the substituents were -Me and -OMe, have been investigated as a function of temperature by 1H NMR spectroscopy. Curvature in the 1/T dependence was evident in most cases. Forced linear extrapolation of the temperature dependence observed over the range of the study yielded Curie plots that include negative slopes with very large positive 1/T intercepts (Cl approximately Br > Me > H) to negative slope with near zero intercept (tri-OMe) to positive slope with very large negative intercept (F, di-OMe). The NMR results were combined with EPR spectroscopic data and curve-fitting procedures based on an expanded Curie law to arrive at a consistent overview of the variety of temperature-dependence behaviors observed. This overview relies upon the premise that, in addition to the ground state observed by EPR spectroscopy, one (or more) thermally accessible excited state(s) are populated to varying degrees over the temperature range of the NMR measurements. If only one excited state is considered, the analysis is consistent with the ground state being a largely intermediate-spin state (S = 3/2) for the majority of the complexes but a largely high-spin state (S = 5/2) for ((2,6-F2)4TPP)FeOClO3 and ((2,6-(OMe)2)4TPP)FeOClO3.