Ligand controlled dioxygen oxidation of rhenium nitrosyl complexes.

The addition of an excess of phenyldiazomethane to chlorobenzene solutions of the cationic dinitrosyl bisphosphine rhenium(-I) complexes [Re(NO)2(PR3)2][BAr(F)4] (R = Cy 1a, R = (i)Pr 1b) gave the corresponding benzylidene complexes [Re{=CH(C6H5)}(NO)2(PR3)2][BAr(F)4] (2a and 2b) in good yields. The treatment of 2b with dioxygen resulted in the oxidation of one of the nitrosyl ligands into the corresponding eta2-nitrito (3b) and nitrato complexes (4b) both in the solid state and in solution. In the case of the tricyclohexylphosphine derivative 2a the analogous conversion was not observed. A mechanism for the reaction of 2b with O2 is proposed which is based on an initial SET to the O2 molecule and subsequent formation of a peroxynitrite complex followed by the formation of a dinuclear mU-N2O4 intermediate. This in turn would undergo fission of the peroxo bond to afford 3b. A related sequence of steps is anticipated for the transformation of 3b to 4b. Furthermore, a similar mechanism seems reasonable for the seemingly topochemical reaction of 2b to 3b and 4b in the solid state. The initial SET to dioxygen and subsequent formation of the peroxynitrite complex is supported by DFT calculations on the trimethylphosphine model complexes [Re=CH{C6H5})(NO)2(PMe3)2]n+ (n = 1 and 2).

Metal nitrosyl reactivity: Acetonitrile-promoted insertion of an alkylidene into a nitrosyl ligand with fission of the NO bond.

Treatment of the complexes [Re(NO)2(PR3)2][BAr(F)4] (R = Cy, 1 a; R = iPr, 1 b) with phenyldiazomethane gave the cationic benzylidene species [Re{CH(C6H5)}(NO)2(PR3)2][BAr(F)4] (2 a and 2 b) in good yields. Upon reaction of 2 a and 2 b with acetonitrile, the consecutive formation of [Re(N[triple bond]CCH3)(N[triple bond]CPh)(NO)(OC(CH3)=NH)(PR3)][BAr(F)4] (3 a and 3 b) and [Re(NCCH3)(OC{CH3}NH{C6H5})(NO)(PR3)2][BAr(F)4] (4 a and 4 b) was observed. The proposed reaction sequence involves the coupling of coordinated NO, carbene and acetonitrile molecules to yield the (1Z)-N-[imino(phenyl)methyl]ethanimidate ligand. The coupling of the nitrosyl and the benzylidene is anticipated to occur first, forming an oximate species. The subsequent acetonitrile addition can be envisaged as a heteroene reaction of the oximate and the acetonitrile ligand yielding 3 a and 3 b, which in turn can cyclise and undergo a prototropic shift initiated by an internal attack of the ethaneimidate ligand on the benzonitrile moiety to afford 4 a and 4 b.

Dicarbonyl-nitrosyl-complexes of rhenium (Re) and technetium (Tc), a potentially new class of compounds for the direct radiolabeling of biomolecules.

Re- and Tc-complexes of the oxidation state (+I) offer a useful synthetic pool for the labeling of biomolecules due to their co-ordination properties and stability, which are superior to compounds of the oxidation state (+V). Based on the results for Tc-tricarbonyl complexes it was the topic of this work to develop an access to similar but higher charged compounds, which could be performed by replacing a neutral [CO]-group by a [NO](+)-group. The resulting Re(I)- and Tc(I)-dicarbonyl-nitrosyl complexes, such as [N(CH2CH3)4][ReX3(CO)2(NO)], show a tendency for co-ordination at carboxylic and amine groups of biomolecules (X = Br, Cl). This was shown with picolinic acid (H-pic), a suitable model for amino acids, forming the neutral complex [ReX(pic)(CO)2(NO)]. In a similar fashion conjugation of [188Re(CO)2(NO)](2+)- or [99mTc(CO)2(NO)](2+)-compounds to proteins or antibodies is feasible. This approach opens a way to a potentially new class of radiopharmaceuticals.

A mixed-valence iron complex of the antitumour drug 6-mercaptopurine: tris(6-mercaptopurine)iron(II) tetrachloroferrate(III) chloride.

Single crystals of the title complex, tris(1, 6-dihydro-9H-purine-6-thione-N(7),S)iron(II) tetrachloroferrate(III) chloride, [Fe(C(5)H(4)N(4)S)(3)][FeCl(4)]Cl, were grown on the surface of solid 6-mercaptopurine monohydrate pellets in a solution of iron(III) chloride. The solution of the hexagonal structure required the application of twin refinement techniques. All the component ions lie on threefold rotation axes. The complex contains distorted octahedral [Fe(C(5)H(4)N(4)S)(3)](2+) cations with three N7/S6-chelating neutral 6-mercaptopurine ligands, tetrahedral [FeCl(4)](-) anions with a mean Fe-Cl distance of 2.189 (1) A, and free chloride ions.

Structure of 2',6'-dihydroxy-4,4'-dimethoxychalcone.

1-(2,6-Dihydroxy-4-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-o ne, C17H16O5, Mr = 300.31, orthorhombic, Pbca, a = 27.903 (3), b = 13.958 (2), c = 7.662 (1) A, V = 2984 (1) A3, Z = 8, D chi = 1.337 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.729 mm-1, F(000) = 1264, T = 295 K, R = 0.040 for 1702 observed reflections. Two intramolecular hydrogen bonds are observed. The hydroxyl H atom at O(6A) is hydrogen bonded to the C(9) carbonyl group with short distances O(6A)...O(9) = 2.406 (3) and O(9)...H(6A) = 1.38 (3), O(6A)--H(6A) = 1.09 (3) A, the angle O(6A)--H(6A)...O(9) is 153 (4) degrees. The other hydrogen bond is of the C--H...O type with distances C(8)...O(2A) = 2.778 (4), H(8)...O(2A) = 2.09 (3) A and the angle around H(8) is 124 (2) degrees. Conjugation is observed between the aromatic rings and the central enone system. The molecule is not planar, the angle between the planes of the phenyl rings being 13.1 (4) degrees. Intermolecular O--H...O bonds with distances O(6A)...O(2A) = 2.689 (2), H(2A)...O(6A) = 1.86 (4) A and angle O(2A)--H...O(6A) = 176 (4) degrees form endless chains of molecules along b.

Structure of 2-methoxy-6-nonyl-1,4-benzoquinone, C16H24O3, a synthetic contact allergen related to the naturally occurring primin.

C16H24O3, Mr = 264.36, triclinic, P1, alpha = 4.167 (1), b = 9.658 (1), c = 19.093 (1) A, alpha = 89.66 (1), beta = 87.27 (1), gamma = 79.07 (1) degrees, V = 753.65 (1) A3, Z = 2, D chi = 1.165 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.595 mm-1, F(000) = 288, T = 295 K, R is 0.047 for 1682 observed unique reflections. The angle between the quinone ring plane and the mean plane defined by the aliphatic nonyl chain atoms is 17.4 (3) degrees. The average Csp3--Csp3 bond distance and corresponding angle of the side chain are 1.522 (3) A and 113.2 (2) degrees. The average dimensions of the quinone ring are C--C 1.485 (3), C = C 1.337 (3), C = O 1.209 (3) A, C--C--C 118.4 (2), C = C--C 120.8 (2), O = C--C 120.8 (2) degrees. Neighboring molecules form dimers across centres of symmetry which are linked by C--H...O hydrogen bonds, with H(3)...O(4i) 2.42 (4), C(3)...O(4i) 3.29 (2) A, and angle C(3)--H(3)...O(4i) 164 (3) degrees. The dimers are held together by van der Waals forces between the nonyl side chains, and by C(16)--H...O(2ii) hydrogen bonds, with H(163)...O(2ii) 2.56 (4), C(16)...O(2ii) 3.357 (3) A, and angle C(16)--H(163)...O(2ii) 140 (3) degrees [(i) -x, 1 -y, -z; (ii) -1 -x, 1-y, -z].

Structure of 6-dodecyl-2-methoxy-1,4-benzoquinone, a new synthetic contact allergen.

C19H30O3, Mr = 306.45, triclinic, P-1, a = 5.453 (1), b = 5.608 (1), c = 30.129 (2) A, alpha = 85.85 (1), beta = 88.66 (1), gamma = 83.02 (1) degree, V = 912.0 (1) A3, Z = 2, Dx = 1.116 Mg m-3, Cu K alpha radiation, lambda = 1.5418 A, mu = 0.548 mm-1, F(000) = 336, T = 296 K, R is 0.040 for 2489 observed unique reflections. The aliphatic side chain is slightly rotated from the quinone ring. The angle between the quinone-ring plane and the mean dodecyl-chain plane is 20.8 (2) degrees. The average Csp3-Csp3 bond lengths and corresponding angles of the side chain are 1.515 (5) A and 113.8 (3) degrees. The average dimensions of the quinone ring are C-C 1.477 (4), C = C 1.337 (4), C = O 1.222 (3) A, C-C-C 118.9 (3), C = C-C 120.6 (3), O = C-C 120.6 (3)degrees. Neighbouring molecules form dimers by C-H...O interactions across centres of symmetry [C(3)...O(3) 3.413 (2) A]. The dimers are linked together via methyl H and carbonyl O along [100] [C(19)...O(3) 3.338 (3) A]; O(3) is a bifurcated acceptor.

Toward a rationalization of the sensitizing potency of substituted p-benzoquinones: reaction of nucleophiles with p-benzoquinones.

MNDO calculations have been carried out for the contact sensitizers 2,6-dimethoxy-1,4-benzoquinone (6) and 2-methoxy-6-methyl-1,4-benzoquinone (10) and for 2,5-dimethoxy-1,4-benzoquinone (7), which is nonallergenic in contrast to thymoquinone (8) (2-methyl-5-isopropyl-1,4-benzoquinone), which is a relatively strong contact allergen. Theoretical results indicate that the conformational flexibility of methoxy groups substituted at the quinone rings influences the electronic properties of these compounds, in particular their reactivity with regard to nucleophiles. According to theory, 6, 10, and 8 should possess a pronounced reactivity toward nucleophiles while 7 should resist nucleophilic attack. Hence, the allergenic capacity of a quinone seems to depend on their binding interactions with nucleophiles such as amino or thio groups of amino acids.

Structure-activity aspects of 4 allergenic sesquiterpene lactones lacking the exocyclic alpha-methylene at the lactone ring.

4 sesquiterpene lactones lacking the exocyclic alpha-methylene at the lactone ring, but possessing further unsaturated centers such as a cyclopentenone ring or an epoxy group, were proved to be sensitizers in guinea pigs. Lack of substitution in the cyclopentenone ring and unsaturation in the side chains appear to be necessary prerequisites for nucleophilic attack. Our results suggest that to the estimated 650 potential sensitizing sesquiterpene lactones of the Compositae family, a further 50 sesquiterpene lactones should be added.

5,8-dihydroxyflavone (primetin) the contact sensitizer of Primula mistassinica Michaux.

5,8-Dihydroxyflavone (primetin) has been shown to be the sensitizer in Primula mistassinica Michaux and probably the source of allergic contact dermatitis in four milkers. Its sensitizing properties as determined in guinea-pigs, are strong. As far as is known this is the first experimental demonstration of the sensitizing potency of a flavone. Presumably the flavone, with its uncommon 5,8-arrangement of hydroxy groups, is oxidized in the skin to the corresponding quinone (primetinquinone). Quinone was prepared from primetin and used for experimental sensitization of guinea-pigs. It also revealed strong sensitizing properties. Cross-reactions were obtained not only with the synthetic quinone in the flavone-sensitive animals but also with primetin in primetinquinone-sensitive guinea-pigs. Preliminary sensitization tests with other flavones have demonstrated that the whole group of flavonoid components should be taken into consideration as potential sensitizers.

Quinonoid constituents as contact sensitisers in Australian blackwood (Acacia melanoxylon RBR).

Australian blackwood (Acacia melanoxylon RBR) is a valuable commercial timber that since 1925 has been incriminated as being injurious to health. In addition to toxic effects numerous cases of allergic contact dermatitis and bronchial asthma have been observed in woodworkers. Several constituents have been identified in recent years, but none of them could be considered as aetiological factors. Sensitizing experiments performed with blackwood heartwood extracts corroborated the described sensitising properties. Chemical studies showed the occurrence of two or possibly three quinones that produced positive skin responses in the sensitised guinea pigs. The main contact allergens were isolated and identified by x-ray analysis. The first, a yellow quinone, was identified as 2,6-dimethoxy-1,4-benzoquinone while the second, a red quinone, has the structure of 6-methoxy-2-methyl-3,5-dihydrobenzofurano-4,7-dion and was named acamelin. Whereas 2, 6-dimethoxy-p-benzoquinone is already known from natural sources, acamelin is new and belongs to the rate group of naturally occurring furanoquinones. Though the obtained sensitising capacity of A melanoxylon RBR in respect of its quinones is not high, it should be considered as a possible source of allergic contact dermatitis, especially as greater amounts of Australian blackwood may enter European countries in the near future.