Gold(I) complexes of water-soluble diphos-type ligands: synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition.

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)(2)] and [L(2)Au]X (X = Cl, PF(6)) are obtained. The ligands used are diphosphanes with azoyl substituents R(2)P(CH(2))(2)PR(2) {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH(2))(2)PRPh {R = 1-methylimidazol-2-yl (3)} and R(2)P(CH(2))(3)PR(2) {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)(2)Au]PF(6) and [(5)(2)Au]PF(6) with intermediate lipophilicity (logD(7.4) = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase.

Gold(I) catalysts with bifunctional P, N ligands.

A series of phosphanes with imidazolyl substituents were prepared as hemilabile PN ligands. The corresponding gold(I) complexes were tested as bifunctional catalysts in the Markovnikov hydration of 1-octyne, as well as in the synthesis of propargylamines by the three component coupling reaction of piperidine, benzaldehyde, and phenylacetylene. While the activity in the hydration of 1-octyne was low, the complexes are potent catalysts for the three component coupling reaction. In homogeneous solution the conversions to the respective propargylamine were considerably higher than under aqueous biphasic conditions. The connectivity of the imidazolyl substituents to the phosphorus atom, their substitution pattern, as well as the number of heteroaromatic substituents have pronounced effects on the catalytic activity of the corresponding gold(I) complexes. Furthermore, formation of polymetallic species with Au(2), Au(3), and Au(4) units has been observed and the solid-state structures of the compounds [(5)(2)Au(3)Cl(2)]Cl and [(3c)(2)Au(4)Cl(2)]Cl(2) (3c = tris(2-isopropylimidazol-4(5)-yl phosphane, 5 = 2-tert-butylimidazol-4(5)-yldiphenyl phosphane) were determined. The gold(I) complexes of imidazol-2-yl phosphane ligands proved to be a novel source for bis(NHC)gold(I) complexes (NHC = N-heterocyclic carbene).

[(C3H4N2)2Au]Cl--a bis protic gold(I)-NHC.

The gold(I) bis-NHC (NHC = imidazol-2-ylidene) parent compound was synthesised in high yield by a three step reaction starting from imidazole. The compound is highly water soluble and stable in concentrated hydrochloric acid.

A new crystal modification of diammonium hydrogen phosphate, (NH(4))(2)(HPO(4)).

The addition of hexa-fluorido-phosphate salts (ammonium, silver, thallium or potassium) is usually used to precipitate complex cations from aqueous solutions. It has long been known that PF(6) (-) is sensitive towards hydrolysis under acidic conditions [Gebala & Jones (1969 ▶). J. Inorg. Nucl. Chem.31, 771-776; Plakhotnyk et al. (2005 ▶). J. Fluorine Chem.126, 27-31]. During the course of our investigation into coinage metal complexes of diphosphine ligands, we used ammonium hexa-fluorido-phosphate in order to crystallize [Ag(diphos-phine)(2)]PF(6) complexes. From these solutions we always obtained needle-like crystals which turned out to be the title compound, 2NH(4) (+)·HPO(4) (2-). It was received as the hydrolysis product of NH(4)PF(6). The crystals are a new modification of diammonium hydrogen phosphate. In contrast to the previously published polymorph [Khan et al. (1972 ▶). Acta Cryst. B28, 2065-2069], Z' of the title compound is 2. In the new modification of the title compound, there are eight mol-ecules of (NH(4))(2)(HPO(4)) in the unit cell. The structure consists of PO(3)OH and NH(4) tetra-hedra, held together by O-H⋯O and N-H⋯O hydrogen bonds.

Determination of the optical properties of anisotropic biological media using an isotropic diffusion model.

We investigate anisotropic light propagation in biological tissue in steady-state and time domains. Monte Carlo simulations performed for tissue that consists of aligned cylindrical and spherical scatterers show that steady-state and time-resolved reflectance depends strongly on the measurement direction relative to the alignment of the cylinder axis. We examine the determination of optical properties using an isotropic diffusion model and find that in the time domain, in contrast to steady-state spatially resolved reflectance measurements, the obtained absorption coefficient does not depend on the measurement direction and is close to the true value. Contrarily, the derived reduced scattering coefficient depends strongly on the measurement direction in both domains. Measurements of the steady-state and time-resolved reflectance from bovine tendon confirm the theoretical findings.