Reaction of cisplatin with

Stein and co-workers have reported the structure of an unusual tetranuclear platinum(II) complex possessing both ammine and carbonato ligands.325 During a study of the reaction of cisplatin with Ag+, followed by the addition of 2 -deoxyuridine to afford platinum blue -like products from aqueous solution (pH < 2), a colorless minor product was isolated from the reaction mixture. X-ray crystallography confirmed that the product was a cyclo tetra-cation... 

Rate constants determined during the reaction of cisplatin with DNA. b kla corresponds to the hydrolysis of CL trans to the c-CeHnNH2, and kib to the hydrolysis of Cl" trans to NH3. 

Reactions between cisplatin and serum albumin are thought to be the main route for platinum binding in human blood plasma. Several clinical and experimental observations have suggested that albumin-bound platinum may be anticancer active [47] [48]. Additionally, albumin binding may reduce some of the side-effects of cisplatin treatment, especially its nephrotoxicity [49]. The reaction of cisplatin with intact and chemically modified recombinant human albumin (rHA), and with HSA (human serum al-... 

Stefanka, Z., Hann, S., Koellensperger, G., Stingeder, G. Investigation of the reaction of cisplatin with methionine in aqueous media using HPLC-ICP-DRCMS. J. Anal. At. Spectrom. 19, 894-898 (2004)... 

Rate constants determined during the reaction of cisplatin with DNA. 

Present double wave can be explained by a reaction of cisplatin with the -SH group(s) of the protein ... 

It has been postulated that carboplatin and its analogs act as prodrugs, reacting with chloride in plasma to give cisplatin. However, the rate of aquation of carboplatin is too slow to account for its in vivo activity (half-life 11 days in water), and the reactions of carboplatin with phosphate, chloride, or water are slower than direct reactions... 

Cisplatin, an anticancer agent used for the treatment of solid tumors, is prepared by the reaction of ammonia with potassium tetrachloroplatinate ... 

A second point of interest is the question of the stoichiometry. For example when cisplatin is reacted with the dinucleotide CG in a 1 1 ratio, the resulting product maybe a 1 1 adduct, but also cw-Pt(NH3)2(CG-N7)2 may be formed (leaving unreacted cisplatin in solution). A detailed study of this system by Chottard8 has made clear that in dilute solutions the 1 1 product is formed only when the concentration of CG is high, is the 1 2 product formed. This agrees with earlier observations of Jordanov66 and Kidani67) for the reactions of cisplatin and CG and GC, respectively. 

Study of the reaction and the resulting products, of cisplatin with other cellular components than DNA. 

Fig. 2) [1], Under neutral conditions, cisplatin can also bind to the N(3) position of cytosine (C) and the N(l) position of A, although these positions are less accessible in a duplex because of base-pairing interactions (Fig. 2) [2], In the reaction of cisplatin or PtCl2(en) (en = ethylenediamine) with salmon sperm DNA, the most abundant adduct was determined to be a 1,2-intrastrand d(G pG ) crosslink (60-65%), while the next most prevalent adduct was a 1,2-intrastrand d(A pG ) crosslink (20-25%) [3] [4]. Because... 

The reaction of cA-[Pt(NH3)2(H20)2]2+ (6), a hydrolysis product of cisplatin, with glycine under mildly acidic conditions, likewise leads to complexes 7 and 8 in which glycine is bound monodentate through oxygen only (Scheme 2). An isomerization occurs, slowly in acidic solution, faster at higher pH, to give the thermodynamically more stable chelate complex 9 [3-5]. 

It has long been known that the products of the reaction of cisplatin (1) with glycinate are the chloride salt of 9, ds-[Pt(NH3)2(gly-A/,(9)]Cl, and, with excess glycinate, m-Pt(NH3)2(gly-A02 (13) [6] [7]. Pivcova etal. [8] [9] have shown that these products are obtained when 1 reacts with glycine under physiological conditions. The crystal structure of the N, O-chelate complex 9 has been determined [10]. 

Reactions of cisplatin and its hydrolytes with longer-chain amino acids +NH3(CH2)nC02 are less relevant to the biological properties of platinum because these compounds are less abundant in vivo. The six- and seven-membered chelate rings formed with /3-alanine (n = 2) and y-aminobutyric acid (n = 3) are progressively less stable kinetically and thermodynamically than the five-membered A/, 0-chelate ring formed with glycine [3]. 

Cisplatin polymer analogs, made through reaction of tetrachloroplatinate with tetramisole, were tested for their ability to inhibit EMC-D viruses that are responsible for the onset of juvenile diabetes symptoms in ICR Swiss male mice [109]. Briefly, the mice were treated with 1, 5, and lOmg/kg. Doses of 1 and 5mg/kg decreased the severity and incidence of virus-induced diabetes in comparison to untreated mice, hi another series of tests, doses of 1 and lOmg/kg were administered 1 day prior to injection of the virus but here there was an increase in the severity and incidence of virus-induced diabetes. Other studies were undertaken showing that the polymer showed different activity profiles than the tetramisole (Scheme 8.29), itself. 

The compound [Pt(NH3)2Cl2] was first prepared In 1845 by two different synthetic routes. The a form of the compound (known as Peyrone s salt) was made by the reaction of [PtC ] " with NH3, while the / form (also called Resiet s second chloride) resulted when [Pt(NH3)4]Cl2 was heated to 250 °C. Many years later, Alfred Werner showed that the two compounds were isomers of each other and suggested that they had square planar molecular geometries. Currently, we know the a form as the anticancer drug cisplatin, c/s-[Pt(NH3)2Cl2], and the form as its geometrical isomer trans-[Pt(NH3)2Cl2]. 

Miller and House have studied the reactions of cisplatin in acidic and basic solution in some detail [14 ]. Although in principle cisplatin can isomerise to transplatin, the process is irrelevant under biological conditions with a half life at 37°C of 1.8 years. In acidic conditions, cisplatin hydrolyses as shown in Scheme 2. 

---