150099-69-7Relevant academic research and scientific papers
Near-IR-triggered, remote-controlled release of metal ions: A novel strategy for caged ions
Atilgan, Ahmet,Tanriverdi E?ik, Esra,Guliyev, Ruslan,Uyar, T. Bilal,Erbas-Cakmak, Sundus,Akkaya, Engin U.
, p. 10678 - 10681 (2014)
A ligand incorporating a dithioethenyl moiety is cleaved into fragments which have a lower metal-ion affinity upon irradiation with low-energy red/near-IR light. The cleavage is a result of singlet oxygen generation which occurs on excitation of the photosensitizer modules. The method has many tunable factors that could make it a satisfactory caging strategy for metal ions. Metal ions on demand: Near-IR irradiation of a designer ligand results in singlet-oxygen-mediated fragmentation with the consequent release of metal ions. The modular nature of the "cage" may herald a new class of agents that could supply chemical effectors on demand.
Design, Synthesis, and Binding Affinity Evaluation of Hoechst 33258 Derivatives for the Development of Sequence-Specific DNA-Based Asymmetric Catalysts
Amirbekyan, Karen,Duchemin, Nicolas,Benedetti, Erica,Joseph, Rinah,Colon, Aude,Markarian, Shiraz A.,Bethge, Lucas,Vonhoff, Stephan,Klussmann, Sven,Cossy, Janine,Vasseur, Jean-Jacques,Arseniyadis, Stellios,Smietana, Michael
, p. 3096 - 3105 (2016)
To date, the concept of DNA-based asymmetric catalysis has been successfully applied to various synthetic transformations by way of hybrid catalysts involving either an intercalator or an integrated ligand anchored through supramolecular interactions. We
Second-generation testosterone-platinum(II) hybrids for site-specific treatment of androgen receptor positive prostate cancer: Design, synthesis and antiproliferative activity
Ouellette, Vincent,C?té, Marie-France,Gaudreault, René C.,Tajmir-Riahi, Heidar-Ali,Bérubé, Gervais
, p. 660 - 666 (2019)
Prostate cancer is the most diagnosed type of cancer in men in Canada. One out of eight men will be stricken with this disease during the course of his life. It is noteworthy that, at initial diagnoses 80–90% of cancers are androgen dependent. Hence, the androgen receptor is a viable biological target to be considered for drug targeting. We have developed a new generation of testosterone-Pt(II) hybrids for site-specific treatment of hormone-dependent prostate cancer. The hybrid molecules are made from testosterone using an eight-step reaction sequence with about 7% overall yield. They are linked with a stronger tether chain between the testosterone moiety and the Pt(II) moiety in comparison to our first generation hybrids. The new hybrids were tested on hormone-dependent and –independent prostate cancer cell lines. The hybrid 3a presents the best antiproliferative activity and was selective on hormone-dependent prostate cancer with IC50 of 2.2 μM on LNCaP (AR+) in comparison to 13.3 μM on PC3 (AR-) and 8.8 μM on DU145 (AR-) prostate cancer cells. On the same cell lines, CDDP displayed IC50 of 2.1 μM, 0.5 μM and 1.0 μM, respectively. Remarkably, hybrid 3a was inactive on both colon carcinoma (HT-29) and normal human adult keratinocyte cells (HaCat) with an IC50 of >25 μM. This is not the case for CDDP showing IC50 of 1.3 μM and 5.1 μM on HT-29 and HaCat cells, respectively. The potential for selective activity on androgen-receptor positive prostate cancer cells is confirmed with hybrid 3a giving new hope for an efficient and less toxic platinum-based treatment of prostate cancer patients.
Charge dependent substrate activity of C3 and N3 functionalized, organometallic technetium and rhenium-labeled thymidine derivatives toward human thymidine kinase 1
Struthers, Harriet,Viertl, David,Kosinski, Marek,Spingler, Bernhard,Buchegger, Franz,Schibli, Roger
, p. 622 - 634 (2010)
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 [18F]3-fluoro-3-deoxythymidine ([ 18F]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 = 99mTc, Re). The click chemistry approach enabled complexes with different structures and overall charges to be 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%).
Redox-Neutral Metal-Free Three-Component Carbonylative Dearomatization of Pyridine Derivatives with CO2
Cerveri, Alessandro,Pace, Stefano,Monari, Magda,Lombardo, Marco,Bandini, Marco
, p. 15272 - 15276 (2019/11/19)
The TBD (1,3,5-triazabicyclodec-5-ene) assisted three-component carbonylation of pyridine-2-methanamines is documented by means of CO2 as a benign CO surrogate. The redox-neutral methodology enables the realization of densely functionalized imi
Synthesis, characterization and catalytic activity of novel ruthenium complexes bearing NNN click based ligands
Sole, Roberto,Bortoluzzi, Marco,Spannenberg, Anke,Tin, Sergey,Beghetto, Valentina,De Vries, Johannes G.
, p. 13580 - 13588 (2019/09/30)
Novel air stable ruthenium(ii) complexes bearing tridentate ligands bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)amine (L1), 1-(1-benzyl-1H-1,2,3-triazol-4-yl)-N-(pyridin-2-ylmethyl)methanamine (L2) or 2-(4-phenyl-1H-1,2,3-triazol-1-yl)-N-(pyridin-2-ylmethyl)ethan-1-amine (L3) were synthesised. The nitrogen based ligands were easily prepared by virtue of click chemistry using cheap and commercially available reagents. The ruthenium complexes were obtained by heating the Ru(PPh3)3Cl2 precursor and the tridentate NNN ligand in toluene under reflux for 2 hours, achieving yields of 82-87%. These complexes were fully characterized by means of NMR, FT-IR and high resolution ESI spectroscopy. The crystal structure of one of the complexes was determined. These complexes showed excellent activity and selectivity in the hydrogenation of ketones and aldehydes. DFT calculations show that complex 3 may react through an outer-sphere catalytic cycle rather than via an inner-sphere mechanism.
Modification and optimization of the bis-picolylamide-based relay protection for carboxylic acids to be cleaved by unusual complexation with Cu2+ salts
Mundinger, Stephan,Jakob, Uwe,Bichovski, Plamen,Bannwarth, Willi
, p. 8968 - 8979,12 (2012/12/11)
A simple modification of our recently published protection scheme for carboxylic acids as amides resulted in a new protecting group with significantly improved properties. It requires shorter reaction times for deprotection and allows us to replace Cu(OTf)2 by CuCl2, indicating at the same time the importance of the nature of the anion of the Cu2+ source. Since the new scheme fulfills all criteria required for an ideal protection group it should find widespread application in synthetic organic chemistry.
A Click procedure with heterogeneous copper to tether technetium-99m chelating agents and rhenium complexes. Evaluation of the chelating properties and biodistribution of the new radiolabelled glucose conjugates
Benoist, Eric,Coulais, Yvon,Almant, Mehdi,Kovensky, Jose,Moreau, Vincent,Lesur, David,Artigau, Marine,Picard, Claude,Galaup, Chantal,Gouin, Sebastien G.
experimental part, p. 26 - 34 (2011/02/25)
An efficient protocol was developed to tether chelating agents and rhenium complexes onto a glucoside scaffold with a heterogeneous copper catalyst via click chemistry. The supported catalyst avoids the formation of unwanted copper complexes during the cyclisation step. The possibility to graft a pre-chelated M(CO)3 core by click chemistry onto a biomolecule was highlighted for the first time. 99mTc(CO)3-glucoconjugates displayed excellent in vitro stability, a fast in vivo blood clearance and a low specific organ uptake or long-term retention in spleen and stomach.
Click-to-chelate : Design and incorporation of triazole-containing metal-chelating systems into biomolecules of diagnostic and therapeutic interest
Struthers, Harriet,Spingler, Bernhard,Mindt, Thomas L.,Schibli, Roger
experimental part, p. 6173 - 6183 (2009/05/27)
The site-specific conjugation of metal chelating systems to biologically relevant molecules is an important contemporary topic in bioinorganic and bioorganometallic chemistry. In this work, we have used the Cu'-catalyzed cycloaddition of azides and terminal alkynes to synthesise novel ligand systems, in which the 1,2,3-triazole is an integral part of the metal chelating system. A diverse set of bidentate alkyne building blocks with different aliphatic and aromatic backbones and various donor groups were prepared. The bidentate alkynes were reacted with benzyl azide in the presence of a catalytic amount of Cu 1 to form tridentate model ligands. The chelators were reacted with [ReBr3(CO)3]2- to form well-defined and stable complexes with different overall charges, structures and hydrophilicities. In all cases tridentate coordination of the ligands, including through N3 of the 1,2,3-triazole ring, was observed. The ligand systems could also be quantitatively radiolabelled with the precursor [99mTc (H 2O)3(CO)3]+ at low ligand concentrations. Similarly the alkynes were reacted with an azido thymidine derivative to form a series of compounds, which could be radiolabeled in situ to form single products. Subsequent incubation of the neutral and cationic organometallic 99mTc thymidine derivatives with human cytosolic thymidine kinase, a key enzyme in tumour proliferation, revealed that only the neutral compounds maintained substrate activity towards the enzyme. Bioconjugation, radiolabelling and enzymatic reactions were successfully performed in a matter of hours. Thus, click chemistry provides an elegant method for rapidly functionalising a biologically relevant molecule with a variety of efficient metal chelators suitable for (radiolabelling with the M(CO) 3 core (M = 99mTc, Re), to offer new potential for technetium-99m in clinical and preclinical tracer development.
