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)

Synthesis and Structure–Property Relationship of meso-Substituted Porphyrin- and Benzoporphyrin–Thiophene Conjugates toward Electrochemical Reduction of Carbon Dioxide

A novel series of ZnII-trans-A2B2 porphyrins and benzoporphyrins bearing phenyl and thiophene-based meso-substituents was successfully synthesized and characterized by spectroscopic and electrochemical techniques. Systematic comparison among the compounds in this series, together with the corresponding A4 analogs previously studied by our group, led to the understanding of the effects of π-conjugated system extension of a porphyrin core through β-fused rings, replacement of the phenyl with the thiophene-based meso-groups, and introduction of additional thiophene rings on thienyl substituents on photophysical and electrochemical properties. Oxidative electropolymerization through bithiophenyl units of both A4 and trans-A2B2 analogs was achieved, resulting in porphyrin– and benzoporphyrin–oligothiophene conjugated polymers, which were characterized by cyclic voltammetry and absorption spectrophotometry. Preliminary studies on catalytic performance toward electrochemical reduction of carbon dioxide (CO2) was described herein to demonstrate the potential of the selected compounds for serving as homogeneous and heterogeneous electrocatalysts for the conversion of CO2 to carbon monoxide (CO)

Conjugation of a novel histidine derivative to biomolecules and labelling with [99mTc(OH2)3(CO)3]+.

The new histidine derivative 3-[1-[3-(9H-fluoren-9-ylmethoxycarbonylamino)-propyl]-1H-imidazol-4-yl]-2-(3-trimethylsilanyl-ethylcarboxyamino)-propionic acid methyl ester (7) has been prepared via alkylation of the histidine urea derivative (7S)-5,6,7,8-tetrahydro-7-(methoxycarbonyl)-5-oxoimidazo-[1,5-c]-pyrimidine (2) with Fmoc-protected 3-iodopropyl-amine, followed by ring opening with 2-trimethylsilylethanol. After Fmoc cleavage by HNEt2, the histidine amine derivative was coupled to biotin, to the pentapeptide leucine-enkephalin and to Vitamin B12-b-acid by amide formation, employing TBTU as the coupling reagent. In order to make the histidine accessible for labelling, the teoc protecting group was removed by either NBu4F (for the biotin conjugate) or by TFA (for the enkephalin and B12 conjugates). Reaction of a 10(-4) M solution of the bioconjugates with [99mTc(H2O)3(CO)3]+ at 50 degrees C for 30 min led to the formation of one single new peak in the HPLC radiochromatogram in each case, confirming quantitative labelling of the respective biomolecules. To assess the nature of the labelled compounds, the rhenium analogues with Re(CO)3 were also synthesised and similar retention times confirmed the identity with the 99mTc labelled conjugates

Derivatives of sodium boranocarbonate as novel CO-releasing molecules (CO-RMs)

Despite the apparent and well-known toxic effects of carbon monoxide (CO), studies on the intriguing biological roles of this molecule are rapidly emerging. Recent investigations have brought to the limelight various physiological effects of CO which include, among others, vasorelaxation and inhibition of organ rejection after transplantation. The importance of CO in biology can be compared with another gas, nitric oxide (NO), an essential and ubiquitous signalling molecule. This parallelism led to the tantalising concept of using CO for therapeutic purposes wherein compounds that transport and deliver this gas to a target tissue would clearly facilitate both the clinical feasibility and the specificity of CO therapy. Sodium boranocarbonate, Na[H3 BCO2H] (1) was the first water-soluble and non-transition metal containing CO-releasing molecule (CO-RM) to be identified. In order to tune the rate of CO release, we modified 1 and synthesised and characterized various derivatives which release CO under physiological conditions but at rates different from the parent compound 1. The synthesis, structure and CO-releasing properties of ester and amide derivatives of 1 will be presented together with some biological studies carried out with a selection of the compounds

Charge dependent substrate activity of C3' and N3 functionalized, organometallic Technetium and Rhenium-labeled thymidine derivatives toward human thymidine kinase 1

Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for the noninvasive imaging of cancer cell proliferation using radiolabeled thymidine analogues such as F-18]3'-fluoro-3'-deoxythymidine (F-18]FLT). A thymidine analogue for single photon emission computed tomography (SPECT), which incorporates the readily available and inexpensive nuclide technetium-99m, would be of considerable practical interest. hTK1 is known to accommodate modification of the structure of the natural substrate thymidine at the positions N3 and C3' and, to a lesser extent, C5. In this work, we used the copper-catalyzed azide-alkyne cycloaddition to synthesize two series of derivatives in which thymidine is functionalized at either the C3' or N3 position with chelating systems suitable for the M(CO)(3) core (M = Tc-99m, Re). The click chemistry approach enabled complexes with different structures and overall charges to he synthesized from a common precursor. Using this strategy, the first organometallic hTK1 substrates in which thymidine is modified at the C3' position were identified. Phosphorylation of the organometallic derivatives was measured relative to thymidine. We have shown that the influence of the overall charge of the derivatives is dependent on the position of functionalization. In the case of the C3'-functionalized derivatives, neutral and anionic substrates were most readily phosphorylated (20-28% of the value for the parent ligand thymidine), whereas for the N3-functionalized derivatives, cationic and neutral complexes were apparently better substrates for the enzyme (14-18%) than anionic derivatives (9%)

Interaction of novel metal complexes with DNA: synthetic and structural aspects

Metal ions bind to nucleic acids at various positions. This binding can be modulated by using metal complexes with appropriate ligands. Novel mono- and especially dinuclear metal complexes could be a powerful tool to detect rare, but still physiologically relevant, forms of DNA, e.g. the left-handed Z-DNA. In this review, our recent research activities in this area of bioinorganic chemistry are summarized. A special emphasis is laid on the synthetic challenges that arose upon the synthesis of the polyamine ligands. Further, some rather unusual approaches to elucidate the solution structure of copper bound to guanosine monophosphate with the help of pulsed EPR techniques like ENDOR and HYSCORE are described

Caesium-templated lanthanoid-containing polyoxotungstates

A family of novel lanthanoid-containing polytungstoarsenate(iii) polyanions with interesting structural features has been isolated: six lacunary {alpha-AsW(9)O(33)} building blocks comprising unusual pyramidal WO(5) units are templated by a caesium cation in a central cavity of the structure