Platinum compounds, and

The organic bases form, like ammonia, crystalline chloroplati-nates with platinic chloride of the general formula BoH,j,PtCl,). By estimating the amount of platinum present in the salt, it is possible to calculate the molecular weight of the platinum compound, and consequently that of the base. 

After this brief introduction, the chapter will focus on solvolysis reactions and acid-base equilibria of various platinum compounds and on species distribution of isomeric [PtCl2(NH3)2] in aqueous solution in Section 2. Binding of platinum compounds to monomeric nucleobase derivatives will be discussed in Section 3, while Section 4 pays attention to the reactions of Pt-nucleobase complexes with different nucleophiles. And finally, the interactions of Pt with DNA and defined oligonucleotides will be discussed in Section 5. 

Muggia FM, Muderpach. Platinum compounds and endometrial cancers focus on carboplatin. Semin Oncol 1994 21(Suppl 2) 35 11. 

Caution. All zero-valent platinum compounds and trialkylphosphines employed here are extremely air sensitive and should be handled in a dry nitrogen or argon atmosphere. The trialkylphosphines are malodorous and toxic, and should be handled with care, in a well-ventilated hood. All solvents should be dried (except ethanolj and distilled under nitrogen. 

Hydrides of Pt(II) are the most numerous of any transition metal hydride group. In addition to the presence of the hydride ligand, the complexes invariably have a coordinated phosphine, and synthetic routes to these compounds using both hydridic and protonic reagents have been reported (I). The pure complexes are usually both air stable and kinetically inert. The purpose of this chapter is to show the diversity of hydrides that can be obtained from protonation reactions on zero-valent and di-valent triphenylphosphine platinum compounds, and to rationalize the type and nature of the product formed from the character of the acid HX. 

Similar pairs of isomers of compounds of nickel as well as of palladium and of platinum with other groups have also been obtained.8 The x-ray study of crystalline potassium nickel dithio-oxalate9 has shown it to be isomorphous with the palladium and platinum compounds and has provided a detailed verification of the planar structure... 

In this section a brief summary of the most important Pt—DNA interactions, including cis-Pt, irans-Pt, and other related platinum compounds, and their relevance for antitumor activity will be presented. For more detailed information the reader is referred to the several reviews that have appeared on this subject during the last 5 years (49-53). 

It is well established that the major cytotoxic effect of platinum-based anticancer dmgs stems from binding of the platinum centre to DNA. The coordination of platinum(II) centres to DNA causes structural modifications which ultimately lead to the induction of apoptosis. Ruthenium compounds were developed as alternatives to platinum compounds and initially their binding to DNA, similarly to platinum compounds, was considered to be central for their anticancer effect. The ruthenium... 

Cellular sensitivity to different platinum compounds and the recognition of the platinum DNA adducts by mismatch repair protein complexes appear to be linked [103]. It may also be significant that hMSH2 is expressed to higher levels in testicular and ovarian tissue than in other organs such as heart, liver and colon [109], Whether or not mismatch repair plays a general role in the anticancer activity of cisplatin still remains debatable, however. Mismatch repair proteins bind to cisplatin-DNA adducts in vitro with weak specificity [109][113]. Although specificity is enhanced when aplat-inum lesion is combined with a mutation [113], it is still less than the affinity of these proteins for the unplatinated mutation [63] [108]. 

Interestingly, more recent MO calculations on silver(I) and copper(I) complexes have indicated that there is much less back donation between these metals and the olefin than in the related platinum compounds, and that the interaction might be primarily electrostatic (see [32], p. 4). 

Horsley (126,127a) has put the relation proposed by Lytle et al. on a more reliable quantitative basis by using accurate calculations of the unoccupied d orbital state using the X4-SW method rather than semiempirical estimates. Using simple deconvolution of the absorption-edge resonance, a relationship has been established between the total vacant d orbital states for a series of platinum compounds and the (corrected) combined areas of the Lu and Lni absorption resonances, rather than the area of the L ii resonance alone, as earlier proposed. This is justified since the LH threshold resonance line arises from transitions from the 2plj2 core level to empty d states of d3/2 character, and the Lm resonance line arises from transitions from the 2p3l2 core level to empty d states of d5/2 character. 

While platinum compounds and paclitaxel comprise the first-line treatment in combination with PEGylated liposomal doxorubicin for patients with ovarian... 

OSHA PEL TWA 0.002 mg(Pt)/mJ ACGIH TLV TWA 0.002 mg(Pt)/m3 DOT CLASSIFICATION 8 Label Corrosive SAFETY PROFILE Poison by intravenous and intraperitoneal routes. Mutation data reported. See PLATINUM COMPOUNDS and CHLORIDES. Incompatible with BrFs. When heated to decomposition it emits toxic fumes of CT. 

Thus, it is extremely important to determine the most effective methods that allow in vivo low drug concentrations. Some basic protocols have been established on restoration of in vivo complex Pt(IV), disintegration polymeric platinum compounds, and slow... 

Platinum compounds and complexes are the most important and commonly used catalysts for hydrosilylation processes [7 - 9]. Platinum catalysts tolerate a variety of functional groups, but some impurities may interact with them leading to catalyst poisoning [10]. This has stimulated much research aimed at employing other transition metal compounds as potential catalysts. For example, Rh(I) complexes are selective and active hydrosilylation catalysts [11] and more resistant to poisoning than the platinum ones [12]. 

Spectroscopic and crystallographic studies of platinum-base complexes give some insight into the reactivity of the platinum compounds and their possible binding sites on DNA. The reactions of the different nucleosides or nucleotides with the chloro and aquo derivatives of O Cs- and trans-DDP have been studied by UV spectroscopy (36), raman difference spectrophotometry (37) and high pressure liquid chromatography (38). For both chloro isomers, the rates of the reactions with various nucleic acid monomers show the following trend GMP > AMP > CMP and dG > dA > dC T, The dichloro and diaquo derivatives react slowly with thymidine and UMP (37) or not at all (38, 39). 

We should note the fact that in the bacterial systems, the substitutionally inert complexes which are mutagenic and active in the repair assay all have effects similar to those of the platinum complexes known to be anti-tumor drugs. Since repair effects are closely correlated with activity of the platinum compounds (17), then the anti-tumor activity could be related to the substitutional inertness of our complexes. We have noted that many of the complexes we have studied are far less bacteriocidal than the platinum compounds, and yet comparable in repair activity. This suggests that further study of substitutionally inert metal complexes may yield anti-tumor drugs which are as effective as the platinum compounds, and yet lack their undesirable toxic side effects. 

Per Teodor Cleve was born in Stockholm in 1840. He studied science at the Uppsala university and started his career as an assistant at this university, in 1874 he was appointed professor of chemistry and held this post until his death. He was the first president, between 1900 and 1905, of the commission which awards the Nobel Prize in chemistry. He began with investigating complex platinum compounds and turned subsequently to rare earth elements. He opposed the ion theory of his contemporary Arrhenius and the novel physico-chemical views of Wilhelm Ostwakl. In the last decade of his life his interest turned towards biology and he was occupied with plankton. He died in Uppsala in 1905 (Boklund 1971). 

Petrow HG, Allen RJ, inventors Protech Co, assignee. Finely particulated colloidal platinum compound and sol for producing the same, and method of preparation of fuel cell electrodes and the like employing the same. United States patent US4044193. 1977 Aug 23. 

Previous exposure to potentially neurotoxic chemotherapeutic agents, such as platinum compounds and vinca alkaloids, does not appear to increase the risk of neurotoxicity with paclitaxel [5 ]. However, patients with co-existing medical illnesses associated with peripheral neuropathy, such as diabetes mellitus and alcohol abuse, may be more likely to develop a peripheral neuropathy. 

So, as long as cis-platin enters exclusively into the tumor cells, it would work wonders. Because tumor cells are in rapid replication mode, they have more chance than ordinary cells to be affected by the platinum compound. And this is the reason for the effectiveness of cis-platin. However, it is likely that cis-platin enters other kinds of cells, too. This would lead to toxic side effects. Indeed, there are some severe side effects including diarrhea and nausea. 

The solution of the phase problem was based on the presence of the third strong site for platinum compound and on the special arrangement of iodine atoms in mercury iodide ion, which in this special case was trigonal. The contribution of this derivative into crystal scattering could be observed up to 3 A. 

Treatment ofWistarRats with Platinum Compounds and Preparation of Paraffin Sections... 

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