Zn2+ and some other divalent metal ions bind to duplex DNA at pHs above 8 and cause a conformational change. This new structure does not bind ethidium, allowing the development of a rapid fluorescence assay. All duplex DNAs, regardless of sequence or G.C content, can form this structure. The rate of formation shows a strong dependence on temperature, pH, and Zn2+ concentration; at 20 degrees C, 1 mM Zn2+, and pH 8.6 the dismutation is half complete in 30 min. Addition of EDTA causes rapid reversion to 'B' DNA, showing that the new conformation retains two strands that are antiparallel. Unlike the ultraviolet or circular dichroism spectra, the nuclear magnetic resonance spectrum was informative since the imino protons of both A.T and G.C base pairs are lost upon addition of a stoichiometric amount of Zn2+. The pitch of the helix was estimated from gel electrophoresis of circular DNAs in the presence of Zn2+ and it contains at least 5% fewer base pairs per turn than 'B' DNA. The transformation is cooperative and shows hysteresis, suggesting that this is a distinct structure and not simply a minor variant of 'B' DNA. It is proposed to call this new structure 'M' DNA because of the intimate involvement of metal ions.

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This paper is dedicated to Professor W . E. Harris on the occasion of his retirementfrom the Universio ofAlberta R. STEPHEN REID and DALLAS L. RABENSTEIN. Can. J. Chem. 59, 1505 (1981. Complexation of methylmercury, CH,Hg(II), by mercaptoacetic acid, mercaptoethanol, mercaptosuccinic acid, cysteine, penicillamine, homocysteine, and N-acetylpenicillamine has been studied by 'H nuclear magnetic resonance spectroscopy. The equilibrium constant for displacement of mercaptoacetic acid from its CH,Hg(II) complex by each of the other thiols was measured over a wide range of pH. From the displacement constants and a literature value for the formation constant of the mercaptoethanol complex of CH,Hg(II), formation constants were calculated for thiol complexes with the other ligands, including microscopic formation constants for cysteine and penicillamine complexes in which the amino groups are protonated and deprotonated. Detailed information on the acid-base chemistry of the free amino and carboxylic acid groups in the complexes is also reported. The formation constants increase as the Bransted basicity of the deprotonated sulfhydryl group increases according to the relation log Kf = pK + 6.86. The conditional formation constants of the CH,Hg(II) complexes are strongly pH dependent due to competitive reactions involving hydrogen and hydroxide ions at low and high pH. The results at physiological pH are discussed with reference to the effectiveness of mercaptosuccinic acid, N-acetylpenicillamine, and penicillamine as antidotes for methylmercury poisoning. Chem. 59, 1505Chem. 59, (1981. Utilisant la spectroscopie de rmn du 'H, on aetudie la complexation du m6thylmercure, CH,Hg(II), par I'acide mercaptoacetique, le mercaptokthanol, I'acide mercaptosuccinique, la cysteine, la penicillamine, I'homocystiine et la N-acetylpenicillamine. Dans un large intervalle de pH, on a mesure la constante d'equilibre de la reaction de diplacement de I'acide mercaptoacetique de son complexe avec le CH,Hg(II) par chacun des autres thiols. En utilisant les constantes de deplacement et les donnees de la littkrature relatives la constante de formation du complexe de CH,Hg(II) avec le mercaptoethanol, on a calcul6 les constantes de formation des complexes de thiol avec d'autres ligands en incluant les constantes de formation microscopiques des complexes de la cysteine et de la penicillamine dans lesquels les groupes amino sont protones et deprotonks. On rapporte egalement une information detaillee de la chimie acide-base des groupes carboxyliques Libres de ces complexes. Les constantes de formation augmentent avec la basicite de Bransted du groupe sulfhydryle dtprotonee selon I'kquation: log K, = pK + 636. Les constantes deformation conditionnelle des complexes de CH,Hg(II) dependent fortement du pH a cause des reactions compktitives qui font intervenir les ions hydrogenes et hydroxyles aux pH faible et eleve. On discute des rksultats au pH physiologique dans le but d'evaluer I'efficacite de I'acide mercaptosuccinique, de la N-acetylpenicillin...

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Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens accompanied by neurotoxicity when given to mice by the intraperitoneal route. However quantitative data revealed protection indices (TD50/ED50) of less than 4 in general. Oral administration of the compounds to rats led to excellent potency in the MES screen accompanied by high protection indices while virtually no activity in the scPTZ test was displayed. These observations support the theory that one large hydrophobic group (in this case the aryl ring) and two electron donor atoms (present in the semicarbazono group) are requirements for protection in the MES screen. In general, the semicarbazones had rapid onsets of action, and one of the ways in which these compounds displayed their anticonvulsant activity is likely to be interaction with chloride channels. Empirical and semiempirical conformational calculations indicated that certain molecular fragments and hydrophobicity of these molecules affect bioactivity.

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