Cu Dips

Many copper(II) complexes, including Cu(DIPS)2 (DIPS = diisopro-pylsalicylate), Cu(salicylate)2, and Cu(Gly-His-Lys), are also active in superoxide dismutation (437, 438), but their use in vivo is limited by dissociation of Cu(II) and binding to natural ligands such as albumin (439). In contrast, the activity of Fe-93 is not affected by albumin (439, 440). 

A voltaic cell is composed of a copper electrode (Cu) dipping into a solution of copper ions (Cu+2) and a mercury electrode in a solution of Hg2+ ions. The cell reaction is... 

One compound, copper(n)di-isopropylsalicylate (Cu-DIPS), has been shown in mice to be very effective in reducing the severity of radiation damage when it is injected up to a few hours after irradiation,... 

Hence, one must conclude that steric requirements do not discriminate between dip and tir , or oq . It is quite striking that ligand catalysis by the mononuclear hydroxo species CuOH+ and Cu(dip)OH+, and by complexes containing the strong base groups Cu(tir)2- and Cu(oq)+ (reminescent of the hypothetical cis-Cu(OH)2 or Cu(OH)+ produce quite similar rates of insertion. It is justified to suppose that a limiting rate has been reached in these cases. 

ELECTRON TRANSFER-OXY RADICAL MECHANISM FOR ANTICANCER AGENTS ETOPOSIDE, Cu DIPS, AND BIS(9-AMINOACRIDINES)... 

The objective of the present study was to determine the electrochemical characteristics of several main categories of antineoplastic agents quinones (etoposide model), metal complexes [Cu(II)(diisopropyl-salicylate) 2 (Cu Dips)], and iminium ions from bis(9-aminoacridines). The results are relevant to the feasibility of ET in vivo. In addition, the relationship of electrochemical behavior to structure and physiological activity is addressed. 

The infrared spectrum was identical to that reported. Cu Dips was synthesized by the procedure of Sorenson s with slight alteration (dried at 110°C for 4 h) m.p.l36-138°C (dec.), reported 142-144°C (dec.). Elemental analysis for C26H34O6CU was, calc. %C, 61.7. %H, 6.7 found %C, 60.3 %H, 6.6. Some Cu Dips solutions were prepared by adding CuCl2 2H20 to a solution of 3,5-diisopropylsalicylic acid (1.0 mM) containing sodium hydroxide (1.0 mM), so that the final concentration of Cu was 0.5 mM, in accord with prior procedures (see references in the metal section). 

Table 1. Cyclic Voltammetry of 3-methoxy o-benzoquinone (5b) and Cu Dips .

In relation to our approach involving ET, we examined the electrochemical behavior of Cu Dips. The solid complex exhibited reduction at +0.27 V in 90% aqueous ethanol (Table 1). The reduction was characterized as irreversible and diffusion controlled on the basis of the Epp/2 value of approximately 203 mV and the constant value of the CF at the scan rates employed (data not shown). Complexes prepared in solution [1 2 Cu(II) to Dips] gave variable irreversible, diffusion-controlled reductions at +0.28 V (six determinations) or +0.21 V (two determinations) (Table 1) in the potential range of +0.84 to 0.0 V. The average Epp/2 values varied from about 190 to 260 mV for the two sets of determinations. Copper(II) chloride dihydrate gave a value of +0.31 V under the same conditions. 

An electron transfer mechanism is advanced for various classes of anticancer agents. The neoplasm is presumably destroyed by induction of oxidative stress. Cyclic voltammetry was performed on some of the main categories quinones (3-methoxy-o-benzoquinone, etoposide model), metal complexes [Cu(II)(3,5-diisopropylsalicylate)2] (Cu Dips) and iminium from bis(9-aminoacridines). Reduction potentials ranged from +0.28 to -0.88 V. Electrochemical behavior is related to structure and physiological activity. 

Electron Transfer Oxy-Radical Mechanism for Anticancer Agents Etoposide, Cu DIPS, and Bis(9-aminoacridines)... 

---