Crystal engineering of the composition of pharmaceutical phases.

The carboxylic acid-pyridine supramolecular heterosynthon can be exploited to predictably generate binary crystalline phases involving rac-ibuprofen, rac-flurbiprofen or aspirin.

Regio- and stereocontrol elements in Rh(II)-catalyzed intramolecular C-H insertion of alpha-diazo-alpha-(phenylsulfonyl)acetamides.

[reaction: see text]. Intramolecular C-H insertion reaction of alpha-diazo-alpha-(phenylsulfonyl)acetamides proceeded with high regio- and stereoselectivities to afford highly functionalized gamma-lactams predominantly or exclusively. The high regioselectivity was attributed to the use of the phenylsulfonyl moiety, which altered electron density at the carbenoid center and exerted a steric effect during the insertion reaction. Also described herein are three control elements to determine regioselectivity, which are amide conformational, stereoelectronic, and substituent effects.

Hydroxylated nanoballs: synthesis, crystal structure, solubility and crystallization on surfaces.

The reaction of equimolar amounts of Cu(NO3)2 and bdc-5-OH (bdc-5-OH = benzene-1,3-dicarboxylate-5-hydroxy) affords hydroxylated nanoballs with high solubility and an ability to form microcrystals on surfaces.

Stepwise Complexation of Ni(II) and Cu(II) Ions by 6,6'-C-spirobi(cyclam) (cyclam = 1,4,8,11-Tetraazacyclotetradecane), L(1). Syntheses and Redox Chemistry of [M(H(2)L(1))]X(4) (M = Cu(2+), Ni(2+)), [Cu(2)(L(1))]X(4), and [CuNi(L(1))]X(4) (X = ClO(4)(-)) and the X-ray Crystal Structure of [Cu(2)(L(1))](ClO(4))(4).

In aqueous HClO(4), the cation [H(4)(L(1))](4+) where L(1) is 6,6'-C-spirobi(cyclam) (cyclam = 1,4,8,11-tetraazacyclotetradecane), complexes Cu(2+) and Ni(2+) ions in a stepwise fashion to form [M(H(2)L(1))](ClO(4))(4) (M = Cu(2+) and Ni(2+)) from which [CuNi(L(1))](ClO(4))(4) has been prepared selectively. The preparation and the structure of [Cu(2)(L(1))](ClO(4))(4) (empirical formula, C(19)H(44)N(8)Cu(2)Cl(4)O(16); space group, triclinic; P&onemacr;; a = 8.1815(6) Å, b = 12.6098(9) Å, c = 16.6565(12) Å, alpha = 80.3890(10) degrees, beta = 76.5840(10) degrees, gamma = 87.1750(10) degrees, V = 1647.9(2) Å(3), and Z = 2; of the 9531 total reflections collected, 6779 reflections with I > 2sigma(I) on least-squares refinement provided final R(1) = 0.0657 and wR(2) = 0.1424) are also reported. The cyclic voltammograms (1.0 M NaCl, 0.1 M H(+); Pt electrodes; all E(1/2) vs NHE) of [M(H(2)L(1))](4+) (M = Cu(2+) and Ni(2+)) ions show single waves for the Cu(II)/Cu(III) couple (E(1/2) = 0.79 V, irreversible) and the Ni(II)/Ni(III) couple (E(1/2) = 0.56 V, reversible), respectively. In CH(3)CN (0.1 M Et(4)NClO(4)), the [Cu(2)(L(1))](4+) ion shows a reversible wave for the Cu(II)-Cu(II)/Cu(II)-Cu(III) couple ((1)E(1/2) = 1.120 V) and an irreversible wave for the Cu(II)-Cu(III)/Cu(III)-Cu(III) couple ((2)E(1/2) = 1.430 V). Similarly, a reversible wave for the Cu(II)-Ni(II)/Cu(II) -Ni(III) couple ((1)E(1/2) = 0.750 V) and an irreversible wave for the Ni(III)-Cu(II)/Ni(III)-Cu(III) couple ((2)E(1/2) = 1.20 V) are observed in the case of the [Cu(II)Ni(II)(L(1))](4+) ion. The [Cu(2)(L(1))](4+) ion (g( perpendicular) = 2.120, g( parallel) = 2.256 and 2.196, A( parallel) = 150 G, and D( parallel) = 75 G) and the mixed valent species [Cu(II)Ni(III)(L(1))](5+) (for Cu(2+), g( perpendicular) = 2.060, g( parallel) = 2.219, and A( parallel) = 100 G; for Ni(3+) in sulfate media, g( perpendicular) = 2.204 and g( parallel) = 1.967) and [Cu(II)Cu(III)(L(1))](5+) (g(xx)() = 1.982, g(yy)() = 2.155, g(zz)() = 2.386, A(yy)() = 80 G, and A(zz)() = 120 G) show dipolar-dipolar interaction. In the mixed-valent ions, due to strong electrostatic repulsion from either the Ni(III) or Cu(III) ions, significantly smaller A( parallel) (or A(zz)()) values are observed for the Cu(2+) ion compared to 200 G in the mononuclear ions. Also, the [Cu(II)Ni(II)(L(1))](4+) in aqueous HClO(4) and the [Ni(2)(L(1))](4+) ion in CH(3)NO(2) show a tendency to reduce perchlorate very slowly.

A Novel Mixed Macrocycle Complex of Nickel: Synthesis, Structure, and Redox Chemistry of [Ni(II)([9]aneN(3))([9]aneS(3))](ClO(4))(2).CHCl(3) ([9]aneN(3) = 1,4,7-Triazacyclononane and [9]aneS(3) = 1,4,7-Trithiacyclononane).

The mixed macrocycle cation, [Ni([9]aneN(3))([9]aneS(3))](2+) (where [9]aneN(3) = 1,4,7-triazacyclononane and [9]aneS(3) = 1,4,7-trithiacyclononane), has been prepared by stepwise complexation of [9]aneN(3) and [9]aneS(3), respectively, to Ni(II) cation. The intermediate [Ni([9]aneN(3))(CH(3)NO(2))(3)](2+) has been isolated and characterized by mass spectrometry and UV-visible spectroscopy. Cyclic voltammetry of [Ni([9]aneN(3))(CH(3)NO(2))(3)](2+) shows a quasireversible wave for the Ni(II/III) couple (E(1/2) = 0.73V vs Fc(+/0)), and the Ni(III) species exhibits an axial ESR spectrum (g( perpendicular) = 2.101 and g( parallel) = 1.985). The structure of [Ni([9]aneN(3))([9]aneS(3))](ClO(4))(2).CHCl(3) has been determined. It crystallizes in monoclinic space group P2(1)/c with a = 13.3911(8) Å, b = 14.4430(9) Å, c = 13.6116(8) Å, beta = 107.2090(10) degrees, V = 2514.7(3) Å(3), and Z = 4. Of the 15 047 reflections collected, 5765 reflections (I > 2sigma(I)) were used in the refinement to obtain a final R(w) = 0.0278 and R(F) = 0.0368. In the cation [Ni([9]aneN(3))([9]aneS(3))](2+), the two macrocycles occupy the trigonal faces of the Ni(2+) ion, imposing a distorted octahedral geometry. Cyclic voltammetry of the complex in CH(3)CN (Pt electrodes, 0.1 M n-Bu(4)NClO(4), 500 mV) shows a quasireversible wave for the Ni(II)/Ni(III) couple (E(1/2) = 0.86V vs Fc(+/0)). Chemical oxidation by NOPF(6) of the cation [Ni([9]aneN(3))([9]aneS(3))](2+) generates a Ni(III) species that shows axial ESR spectrum with g( perpendicular) = 2.106 and g( parallel) = 2.063. No characteristic reduction wave was observed in either CH(3)CN or CH(3)NO(2) media.

1-(p-carbamoylphenyl)-3,3-dimethyl-triazene, an antitumour agent.

In the crystal structure of the title compound, 4-(3,3-dimethyl-1-triazeno)benzamide, C9H12N4O, (2), the N = N double bond [1.282 (8) A] is 0.030 A shorter than the N--N single bond [1.312 (8) A], but both bonds are shorter than an isolated N--N single bond suggesting that there is double-bond character in each N--N bond, although it is unequally distributed. The molecule adopts a trans geometry around the N = N bond, but there is a significant deviation from planarity between the benzene ring and the plane of the triazene moiety. Compound (2) forms chains in the solid state in which the molecules are linked by C = O...H--N hydrogen bonds between carbamoyl groups. These chains are cross-linked into sheets by hydrogen bonding between the second N--H moiety and triazene units in adjacent chains.

Uptake, distribution, and metabolism of trivalent arsenic in the pregnant mouse.

To investigate the distribution of trivalent arsenic (arsenite) in the pregnant rodent, CD-1 mice were dosed with sodium arsenite by ip injection or by gavage on gestation d 18 (copulation plug day = d 1). Doses were 8 (ip) or 25 (po) mg/kg, and samples of maternal blood, liver, and kidneys, as well as fetuses and pooled placentas, were analyzed for total arsenic at intervals of up to 24 h. Fetal tissue was also analyzed for relative proportions of inorganic arsenic and methylated metabolites. Arsenic uptake was significantly greater in the injected mice and their fetuses (as a proportion of the administered dose), with levels highest at 10 min to 4 h in maternal tissues and 24 h in fetuses. Peak maternal arsenic levels (as microgram/g or microgram/ml) ranged from 2.36 (blood) to 26.15 (liver) for the ip injected and 1.25 (blood) to 17.64 (liver) for the gavaged treatment group. The rate of arsenic elimination from maternal samples was not significantly influenced by administration route, with first-order elimination rate constants (k) of 0.215 and 0.234 h-1 for the po and ip dosed mice, respectively. Fetal tissue arsenic peaks were 2.10 and 0.77 micrograms/g for the ip and po treatment groups, respectively. The proportion of methylated arsenic in fetuses increased to 79% in the ip treatment group and 88% in the po group by 24 h. Such results show that much of the arsenic reaching the mouse fetus has been methylated to less toxic metabolites. They also confirm that assumptions made regarding hazard to the fetus must reflect the likelihood that a portion of any maternal dose of inorganic arsenite reaching a fetus may have been methylated, and they support previous findings that arsenite is toxic to the conceptus at lower doses when given by injection than by gavage.

Distribution, metabolism, and fetal uptake of pentavalent arsenic in pregnant mice following oral or intraperitoneal administration.

Pregnant CD-1 mice were treated with 20 (i.p.) or 40 (p.o.) mg/kg sodium arsenate on gestation day 18 (plug = day 1). Individual fetuses, pooled placentas and maternal blood, urine, liver, and kidneys were obtained from three or more litters at intervals up to 24 hours following treatment. Acid-digested samples were analyzed for total arsenic by hydride generation atomic absorption spectrophotometry. The rate of arsenic elimination from maternal samples was not influenced by administration route. First-order elimination followed a brief period of distribution, and the biological half-life was approximately 10 hours. Arsenic was found in most samples, with mean peak concentrations expressed as micrograms As/gm (wet wt.) or /ml (values listed are post-treatment sampling times in minutes or hours and concentrations for i.p. and for p.o. treated groups, respectively) as follows: fetuses-2, 3.5; 6, 0.8, placentas-2, 9.3; 1, 2.3, blood-10 minutes, 6.9; 1, 2.0, urine-1, 712; 2, 342, kidney-20 minutes, 25.4; 1, 11.0, liver-0.5, 7.9; 1, 11.7. By 24 hours, arsenic levels in fetuses and placentas had declined to 0.22 microgram/gm and 0.74 microgram/gm for i.p. and 0.33 microgram/gm and 0.57 microgram/gm for p.o. treatments, respectively. Fetal arsenic uptake and loss were more rapid following i.p. than p.o. treatments, and although the i.p. dose was only half that used p.o., peak fetal As+5 was almost fivefold higher following i.p. treatment. These results agree with the finding that oral dosing of pregnant mice with arsenate has less effect on the conceptus than does treatment by injection.(ABSTRACT TRUNCATED AT 250 WORDS)