RAPTA derivatives
Several derivatives of RAPTA were synthesized, and two of the most notable are [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) and [Ru(η6-toluene)Cl2(pta)] (RAPTA-T).
RAPTA (ruthenium arene PTA) is a class of experimental cancer drugs. They consist of a central ruthenium(II) atom complexed to an arene group, chlorides, and 1,3,5-triaza-7-phosphaadamantane (PTA) forming an organoruthenium half-sandwich compound. Other related ruthenium anti-cancer drugs include NAMI-A, KP1019 and BOLD-100.
It is envisaged that RAPTA derivatives have the “piano stool” structure like others organometallic half-sandwich compound. [1] This is observed by the crystal structure of RAPTA-C which exhibits the archetypal half-sandwich structure. [2] The PTA ligand was designed to make the complexes more soluble in water, and the two labile chlorido ligands can exchange to aquo ligand in the presence of water. [3]
In a typical synthesis, [Ru (η6-p-cymene)Cl2] is reacted with 2 equivalents of PTA for 24 hours under reflux in methanol to yield to [Ru(η6-p-cymene)Cl2(pta)]. [4]
Several derivatives of RAPTA were synthesized, and two of the most notable are [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) and [Ru(η6-toluene)Cl2(pta)] (RAPTA-T).
At first, RAPTA was anticipated to hydrolyze and interact with DNA to target primary tumors, which is similar to the platinum analogue cisplatin. Studies showed that adducts form between RAPTA compounds and proteins (especially cathepsin B and thioredoxin reductase(TrxR)). [5] [6] Moreover, the reactivity of RAPTA in the presence of protein was totally different than that of cisplatin. [7] In vitro studies showed that cytotoxicity of RAPTA derivatives was much less as compared to cisplatin, and some RAPTA compounds are not even cytotoxic to healthy cells. [8] Surprisingly, both RAPTA-C and RAPTA-T showed the ability to inhibit lung metastasis in mice bearing middle cerebral artery mammary carcinoma (by measuring the number and weight of the metastases), whilst having small effect on primary tumor. [9] The only ruthenium complex which proves the ability against metastasis was NAMI-A, and this work has high practical application in chemotherapy since the removal of primary tumor can be done through frequent surgery while the number of metastasis treatments are limited. [10]
Ruthenium(III) chloride is the chemical compound with the formula RuCl3. "Ruthenium(III) chloride" more commonly refers to the hydrate RuCl3·xH2O. Both the anhydrous and hydrated species are dark brown or black solids. The hydrate, with a varying proportion of water of crystallization, often approximating to a trihydrate, is a commonly used starting material in ruthenium chemistry.
p-Cymene is a naturally occurring aromatic organic compound. It is classified as an alkylbenzene related to monocyclic monoterpenes. Its structure consists of a benzene ring para-substituted with a methyl group and an isopropyl group. p-Cymene is insoluble in water, but miscible with organic solvents.
Titanocene dichloride is the organotitanium compound with the formula (η5-C5H5)2TiCl2, commonly abbreviated as Cp2TiCl2. This metallocene is a common reagent in organometallic and organic synthesis. It exists as a bright red solid that slowly hydrolyzes in air. It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a chemotherapy drug.
In chemistry, transfer hydrogenation is a chemical reaction involving the addition of hydrogen to a compound from a source other than molecular H2. It is applied in laboratory and industrial organic synthesis to saturate organic compounds and reduce ketones to alcohols, and imines to amines. It avoids the need for high-pressure molecular H2 used in conventional hydrogenation. Transfer hydrogenation usually occurs at mild temperature and pressure conditions using organic or organometallic catalysts, many of which are chiral, allowing efficient asymmetric synthesis. It uses hydrogen donor compounds such as formic acid, isopropanol or dihydroanthracene, dehydrogenating them to CO2, acetone, or anthracene respectively. Often, the donor molecules also function as solvents for the reaction. A large scale application of transfer hydrogenation is coal liquefaction using "donor solvents" such as tetralin.
In organometallic chemistry, a sandwich compound is a chemical compound featuring a metal bound by haptic, covalent bonds to two arene (ring) ligands. The arenes have the formula CnHn, substituted derivatives and heterocyclic derivatives. Because the metal is usually situated between the two rings, it is said to be "sandwiched". A special class of sandwich complexes are the metallocenes.
Dichlorotetrakis(dimethyl sulfoxide) ruthenium(II) describes coordination compounds with the formula RuCl2(dmso)4, where DMSO is dimethylsulfoxide. Both cis and trans isomers are known, but the cis isomer is more common. The cis isomer is a yellow, air-stable solid that is soluble in some organic solvents. These sulfoxide complexes are used in the synthesis of various ruthenium(ii) complexes. They have also attracted attention as possible anti-cancer drugs.
(Cymene)ruthenium dichloride dimer is the organometallic compound with the formula [(cymene)RuCl2]2. This red-coloured, diamagnetic solid is a reagent in organometallic chemistry and homogeneous catalysis. The complex is structurally similar to (benzene)ruthenium dichloride dimer.
Chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium is the organoruthenium half-sandwich compound with formula RuCl(PPh3)2(C5H5). It as an air-stable orange crystalline solid that is used in a variety of organometallic synthetic and catalytic transformations. The compound has idealized Cs symmetry. It is soluble in chloroform, dichloromethane, and acetone.
Organoruthenium chemistry is the chemistry of organometallic compounds containing a carbon to ruthenium chemical bond. Several organoruthenium catalysts are of commercial interest and organoruthenium compounds have been considered for cancer therapy. The chemistry has some stoichiometric similarities with organoiron chemistry, as iron is directly above ruthenium in group 8 of the periodic table. The most important reagents for the introduction of ruthenium are ruthenium(III) chloride and triruthenium dodecacarbonyl.
Organovanadium chemistry is the chemistry of organometallic compounds containing a carbon (C) to vanadium (V) chemical bond. Organovanadium compounds find only minor use as reagents in organic synthesis but are significant for polymer chemistry as catalysts.
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Gábor Laurenczy is a Hungarian-Swiss chemist and academic. He is a Professor Emeritus at the École Polytechnique Fédérale de Lausanne. He is academician, External Member of the Hungarian Academy of Sciences.
NAMI-A is the imidazolium]] salt of the coordination complex [RuCl4(dmso)(C3N2H4)]− where dmso is dimethylsulfoxide and C3N2H4 is imidazole Together with KP1019 and BOLD-100, NAMI-A has been investigated as an anticancer agent.
Ruthenium anti-cancer drugs are coordination complexes of ruthenium complexes that have anticancer properties. They promise to provide alternatives to platinum-based drugs for anticancer therapy. No ruthenium anti-cancer drug has been commercialized.
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Christian G. Hartinger is an Austrian-born New Zealand bioinorganic chemist known for his work in metal-based anticancer drugs. In 2022 he was elected a Fellow of the Royal Society Te Apārangi.
(Benzene)ruthenium dichloride dimer is the organoruthenium compound with the formula [(C6H6)RuCl2]2. This red-coloured, diamagnetic solid is a reagent in organometallic chemistry and homogeneous catalysis.
Metal arene complexes are organometallic compounds of the formula (C6R6)xMLy. Common classes are of the type (C6R6)ML3 and (C6R6)2M. These compounds are reagents in inorganic and organic synthesis. The principles that describe arene complexes extend to related organic ligands such as many heterocycles (e.g. thiophene) and polycyclic aromatic compounds (e.g. naphthalene).
1,3,5-Triaza-7-phosphaadamantane (PTA) is a chemical compound with the formula C6H12N3P, a product of the substitution of a nitrogen atom of hexamethylenetetramine with a phosphorus atom. It is soluble in water, methanol, trichloromethane, acetone, ethanol and DMSO, insoluble in hydrocarbon solvent. As a reagent in organic synthesis, it is used as a ligand for transition metal complexes and as a catalyst for Baylis–Hillman reactions.