Platinum specific derivatives

We recently reported the synthesis of polymeric platinum II derivatives of cis-dichlorodiamineplatinum II, cis-DDP (2 1,2). These polyamines (2) exhibit good inhibition towards a wide range of tumor cells including L929, WISH and HeLa cell lines with good cell differentiation. Some extend the life of (induced) terminally ill cancerous mice by 50%. Further the polyamines exhibit activity towards virus at concentration levels where the cells are unaffected. Recent biological studies are aimed at evaluation of certain polyamines on inhibiting select tumors and viruses for specific disease control. 

Catalytic oxidation ia the presence of metals is claimed as both nonspecific and specific for the 6-hydoxyl depending on the metals used and the conditions employed for the oxidation. Nonspecific oxidation is achieved with silver or copper and oxygen (243), and noble metals with bismuth and oxygen (244). Specific oxidation is claimed with platinum at pH 6—10 ia water ia the presence of oxygen (245). Related patents to water-soluble carboxylated derivatives of starch are Hoechst s on the oxidation of ethoxylated starch and another on the oxidation of sucrose to a tricarboxyhc acid. AH the oxidations are specific to primary hydroxyls and are with a platinum catalyst at pH near neutraUty ia the presence of oxygen (246,247). Polysaccharides as raw materials ia the detergent iadustry have been reviewed (248). 

A further effect which has been known for many years is that of anions, which are specifically adsorbed at high anodic potentials on platinum, on the products of the oxidation of carboxylate ions. For example, carbonium ion-derived products can be obtained in the presence of such specific adsorption and this demands a complete change in reaction route (Fioshin and Avrutskaya, 1967 Glasstone and Hickling, 1934). 

Cositecan (Karenitecin , BNP 1350) 54 (BioNumerik and ASKA Pharmaceutical) is currently being evaluated in a Phase III trial for the treatment of patients with advanced ovarian cancer who have become resistant to platinum and taxane drugs.110 Cositecan 54,111 114 which is also being evaluated against solid tumours in a Phase I trial, is an orally bioavailable, lipophilic 7-[2-(tri-methylsilyl)ethyl] derivative of camptothecin 55 which is less sensitive to both common and camptothecin-specific resistance mechanisms. Camptothecin 55 was first isolated in 1958 from Camptotheca acuminata (Nyssaceae) and its structure was reported in 1966.115 117 Camptothecin 55 was later shown to be a topoisomerase I inhibitor two camptothecin derivatives, topotecan and iri-notecan, are approved for chemotherapy use. 

In addition to pyridinium based catalysts and cyclodextrin derivatives, some special compounds have also been reported to be useful inverse PT catalysts for specific reactions. Te-tramethyl ammonium salts that are ineffective as PT catalysts due to their high solubility in the aqueous phase have been found to be effective inverse PT catalysts in some systems. Some metal compounds like platinum, palladium, and rhodium can strongly complex with water-soluble ligands such as the trisodium salt of triphenylphosphine trisulfonic acid, and act as effective inverse PT catalysts. These complexes are soluble in the aqueous phase only and, thus are easily recov-... 

In the case of the compound derived from 3-aminoquinuclidine (trichloro(3-aminoquinuclidinium)platinum(II), or QTP) we have tried to resolve the structural question by examination of infrared spectra in the N-H stretching region. Comparisons of spectra for 3-aminoquinuclidine, its mono- and di-protonated hydrochlorides, and QTP suggest that in the platinum complex it is the -NH group which is protonated. Specifically, a broad and intense band at ca 2800 cm which can be assigned to the protonated tertiary amine group in the mono- and di-hydrochloride is absent from QTP. Infrared spectra thus suggest structure III for QTP. 

A detailed computational model was developed for several different iimovative designs for the preferential carbon monoxide (CO) oxidation reactor using a kinetic mechanism and reaction sequence derived from a micro-kinetic model and literature data for the specific adsorption coefficients and kinetic parameters for a platinum-based catalyst. 

Supported platinum and palladium catalysts were prepared by soaking a preformed alumina support (Kaiser KC/SAF gel-derived alumina, 250 m2/g, %-inch spheres) in concentrated aqueous solutions of the appropriate metal chloride. The catalysts were calcined at 600 °C in air before use. Specific metal surface areas were measured by titration of chemisorbed oxygen with hydrogen (I, 2). Prior to the adsorption measurement, each sample was reduced 1 hr in H2 at 500°C, evacuated 1 hr at 500°C, and exposed overnight to 02 at room temperature. Elemental distributions in the catalyst pellets were determined by electron microprobe. 

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