The electroplated magnetic alloys ͑1.0T Ni 80 Fe 20 , 1.6T Ni 45 Fe 55 , 2.4T Co 40 Fe 60 ͒, obtained in the presence of saccharin, and sputtered magnetic alloys of the same composition showed dramatically different corrosion properties at pH 5.9. The higher corrosion susceptibility of electroplated magnetic alloys, known for many years, was generally attributed to sulfur inclusions into the deposit. However, there was no direct evidence of the structure of sulfur-containing molecules included in deposit. We have analyzed electroplated, EP-CoFe, and sputtered, SP-CoFe, magnetic films using electrochemical, secondary ion mass spectroscopy, X-ray photoelectron spectroscopy ͑XPS͒, and high-pressure liquid chromatography ͑HPLC͒ techniques. The analysis of electroplated CoFe films obtained in the presence of saccharin revealed saccharin, benzamide, o-toluenbenzamide ͑HPLC͒ and metal sulfides ͑XPS͒ in EP-CoFe deposit. The proposed mechanism for saccharin transformation to metal sulfides involves four steps: ͑i͒ a reductive cleavage of C-S bond in saccharin giving rise to benzamido sulfinate, ͑ii͒ a desulfurization step leading to benzamide and sulfur dioxide, ͑iii͒ an electrochemical reduction of sulfur dioxide to hydrogen sulfide, and ͑iv͒ a reaction between H 2 S and M +2 ͑M = CO, Fe͒ to metal sulfides. The higher corrosion susceptibility of EP-CoFe magnetic alloys than SP-CoFe magnetic alloys is discussed in terms of the mechanism of sulfur-assisted corrosion.Saccharin is an additive that has been widely used for more than three decades in the industry for electrodeposition of magnetic alloys such as 1.0T NiFe, 1 1.6T NiFe, 2 and 1.8T CoNiFe, 3-5 used as writer materials in the recording heads. It has been reported that saccharin reduces tensile stress, 1,6 grain size, 6 roughness, 7 and coercivity 1-6 of magnetic materials. However, it is also known that electroplated magnetic films in the presence of saccharin show higher corrosion susceptibility than magnetic films deposited without saccharin or sputtered by vacuum deposition. [8][9][10][11] The higher corrosion susceptibility of electroplated magnetic alloys was generally attributed to sulfur inclusions into the deposit. Notably, the sulfur in the deposit was associated with saccharin present in the plating bath but there was no direct evidence about the structure of the sulfurcontaining molecules included in the deposit.The CoFe magnetic alloys with 50-70% Fe have the highest magnetic moment of 2.4 Tesla 12 and can be obtained electrochemically in the presence of saccharin as an organic additive. Such CoFe alloy has also very high corrosion susceptibility and when used as a writer element in recording heads it can have detrimental effects on performance. Attempts were made to electrodeposit 2.4T CoFe alloys without additives 13 or by replacing saccharin with another organic additive. 14-16 However, replacing saccharin is a difficult task. It is very often a trade-off between good corrosion resistance on one side, and high stress, roughness, grain size, and coer...

Metabolic activation of estradiol leading to the formation of catechol estrogens is believed to be a prerequisite for its genotoxic effects. Previous studies have shown that 3,4-estrone quinone (3,4-EQ) can redox-cycle and is capable of inducing exclusively single-strand DNA breaks in MCF-7 breast cancer cells [Nutter et al. (1991) J. Biol. Chem. 226, 16380-16386]. These studies, however, could not provide conclusive evidence about the mechanism of estrogen carcinogenesis. In order to explore this in more detail, we have shown previously that 3,4-EQ can react with adenine under electrochemical reductive conditions to yield an estrogen-nucleic acid adduct [Abul-Hajj et al. (1995) J. Am. Chem. Soc. 117, 6144-6145]. In this paper, we report the synthesis and identification of seven estrogen-nucleic acid adducts obtained from reaction of 3,4-EQ with adenine, thymine, and cytosine. Initial purification of reaction mixtures using TLC followed by HPLC gave sufficient quantities of reaction products for identification using 1H-NMR and mass spectral determinations. Reaction of 3,4-EQ with adenine, thymine, and cytosine gave the following estrogen-nucleic acid adducts: 8-(4-hydoxyestrone-1-yl)adenine, 3-adenylimino-1,5(10)-estradiene-4,17-dione,4-adenylimino-1, 5(10)-estradiene-3,17-dione, N1- [4-hydroxyestrone-1(alpha,beta)-yl]thymine, N4-(4-hydroxyestrone-1- yl)cytosine, and N4-(4-hydroxy- estrone-2-yl)cytosine. No reaction products were obtained with guanine presumably due to poor solubility in DMF.

Estrogens have been shown to induce mammary, pituitary, cervical, and uterine tumors in rats, mice, and guinea pigs.1 Estradiol and other estrogens induce renal carcinoma in 80-100% of Syrian hamsters within 6-8 months.* 12 Although the exact mechanism for carcinogenesis induced by estrogenic compounds is not fully understood, it is generally believed that metabolic activation of estradiol leading to the formation of catechol estrogens is a prerequisite for its genotoxic activity.3 It has been proposed that the steroid estrogens may generate reactive intermediates, particularly arene oxides4 and quiñones/ semiquinones, during their metabolism in analogy to the metabolism of aromatic polycyclic hydrocarbons which are known to be implicated in carcinogenesis.5 Thus, the estrogen o-quinones/semiquinones produced by the oxidation of catechol estrogens by phenol oxidase,6 prostaglandin H synthetase,7 and cytochrome P-450 oxidase8 have the potential to be cytotoxic and genotoxic. Studies in our laboratories have shown that 3,4estronequinone (3,4-EQ), which can "redox-cycle" leading to the formation of hydrogen peroxide, the hydroxyl radical, and the semiquinone of 3,4-EQ,9b was capable of inducing exclusively single strand DNA breaks/alkali-labile sites in a human breast cancer cell line.93 Although hydroxyl radical production was found to correlate with 3,4-EQ-induced DNA damage,9c the production of hydrogen peroxide and the hydroxyl radical may only be an indicator of the metabolism of 3,4-EQ to a DNA-damaging species. Thus, two potential mechanisms may be involved in the carcinogenicity/toxicity of estrogen quiñones: ary latí on of macromolecules including proteins, DNA and RNA, and generation of reactive oxygen species (ROS). While Michael addition products from reaction of amino acid nucleophiles are well documented,10 *many previous attempts at

Reaction of 3,4-estrone o-quinone (3,4-EQ) with several amino acid side chain mimics, including 4-ethylphenol, 4-methylimidazole, acetic acid, and propanethiol, gave a mixture of several products including the catechol, Michael addition products, and dimeric products of the catechol. On the other hand, several other amino acid side chain mimics, including ethanol, acetamide, 1-ethylguanidine, and 3-methylindole, did not result in any addition products or catechol formation. Michael addition to 3,4-EQ with 4-methylimidazole, acetate, and 4-ethyl phenoxide resulted in 1,4-addition, leading to C-1 adducts while reaction with propanethiol gave the C-2 addition product.

The carcinogenicity of estrogens in rodents and man has been attributed to either alkylation of cellular macromolecules and/or redox-cycling, generation of active radicals, and DNA damage. Metabolic activation of estradiol leading to the formation of catechol estrogens is believed to be a prerequisite for its genotoxic effects. 4-Hydroxyestradiol, although not 2-hydroxyestradiol, is a potent inducer of tumors in hamsters. Previous studies have shown that 3,4-estrone quinone can redox-cycle and is capable of inducing exclusively single strand DNA breaks in MCF-7 breast cancer cells, as well as react with various nucleophiles (thiol, imidazole, amino, phenolate, and acetoxy) to give Michael addition products. These results support the possible involvement of 3,4-catechol/quinone estrogens in estrogen's carcinogenicity. To explain the decreased carcinogenicity of 2-hydroxyestrogens, the reactions of 2,3-estrone quinone (2,3-EQ) with nucleophiles were investigated. Reactions of 4-methylimidazole with 2,3-EQ gave a complex mixture of products leadng to the formation of the catechol, C-O dimerization product, and a 1,6-Michael addition product identified as the 1-(4-methylimidazolo)-2-hydroxyestrone. Reactions of 2,3-EQ under mildly basic conditions with either ethyl phenolate or acetate gave several products which were characterized as the C-O and C-C dimers, catechol, and 3,5-dihydroxy-1(10), 3-estradiene-2, 17-dione. No Michael addition products were detected under these experimental conditions. The same products were also observed during the synthesis of 2,3-EQ, which led us to postulate that the lack of carcinogenicity of 2-hydroxyestrogens may be related to the increased reactivity and decreased stability of the quinone under physiological conditions. These results are contrasted with those obtained with 3,4-EQ which is much more stable and therefore could diffuse from the site of formation to the target tissue. These results along with rapid methylation and clearance may be very likely explanations for the decreased carcinogenicity of 2-hydroxyestrogens.