Radiosensitizer Complexes

The rationale for electron affinity has been summarized Section 8.2.1. The oxidizing properties of the complexes discussed above are metal-centered. Ligands which contain redox-active sites may have their chemical and biological properties modified by complexation, for example the nitro-aromatics with ligating properties. 

Initial results on cw-[PtCl2(metronidazole)2] (abbreviated FLAP from Flagyl-Platinum) were very promising with a reported ER of 2.4 and little toxicity [50] but later studies [48, 51, 52] failed to corroborate this finding 

Chemical and biological data for some metal—nitroimidazole complexes 

The complexation of the substituted thiazole, 2-amino-5-nitrothiazole (ANT) has also been examined  

A further set of complexes which may be mentioned are the platinum nitroxyls, derived from piperidine and pyrollidine A -oxides [63,64]  

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In essence, metal—radiosensitizer complexes contain a redox-active ligand combined to the metal. Enhanced radiosensitization could occur through... 

Sulphide and sulphoxide complexes have been extensively studied since cis-RuC12(DMSO)4 (DMSO, dimethyl sulphoxide, (Me)2SO) was found to have anti-tumour properties and to be a precessor for radiosensitizing agents. Such complexes can act as catalysts for the oxidation of sulphides with molecular oxygen. 

Again both S- and O-bonded sulphoxides are found. mer-[RuCl3(Ph2SO)3] has one S-bonded sulphoxide and two O-bonded sulphoxides (one trans to Cl, one trans to S) [112], The imidazole-substituted complexes are being studied as possible radiosensitizers and for anti-tumour activity. 

Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y (2004) Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116 51-61 Taneja N, Davis M, Choy JS, Beckett MA, Singh R, Kron SJ, Weichselbaum RR (2004) Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy. J Biol Chem 279 2273-2280... 

Douple EB, Richmond RC. Platinum complexes as radiosensitizers of hypoxic mammalian cells. Br J Cancer 1978 37(Suppl III) 98—102. 

Zimbrick JD, Aruni S, Richmond RC. Studies on radiosensitization of Escherichia coli cells by cis-platinum complexes. Int J Radiat Oncol Biol Phys 1979 5 1351-1354. 

Chibber R. Radiosensitizing and cytotoxic action of some Rh(II) carboxylates in vitro a comparison with Pt(II) complexes. Ph.D. Dissertation 1984 Department of Chemistry, Hatfield Polytechnic, Hatfield, Hertfordshire, England. 

Stratford IJ, Williamson C, Adams GE. Combination studies with misonidazole and a cis-platinum complex cytotoxicity and radiosensitization in vitro. BrJ Cancer 1980 41 517-522. 

In most organs and tissues the injury and the underlying mechanism for that injury are complex and may involve a combination of events. The extent and severity of this tissue injury are dependent upon the radiosensitivity of the various cell types in that organ system. Rubin and Casarett (1968) describe and schematically display the events following radiation in several organ system types. These include a rapid renewal system, such as the gastrointestinal mucosa a slow renewal system, such as the pulmonary epithelium and a nonrenewal system, such as neural or muscle tissue. In the... 

Muindi JRF, Sinha BK, Gianni L, Myers CE (1984) Hydroxyl radical production and DNA damage induced by anthracycline-iron complex. FEBS Lett 172 226-230 Mujica V, Nitzan A, Mao Y, Davis W, Kemp M, Roitberg A, Ratner MA (1999) Electron transfer in molecules and molecular wires geometry dependence, coherent transfer, and control. In Jortner J, Bixon M (eds) Electron transfer From isolated molecules to biomolecules. Part Two, Advances in Chemical Physics Series, Vol 107. Wiley, New York, pp 403-428 Mullenger L, Ormerod MG (1969) The radiosensitization of Micrococcus sodonensis by N-ethyl ma-leimide. Int J Radiat Biol 15 259-269... 

Stillman MJ, Shaw CF III, Suzuki KT (1992) Metallothioneins. Synthesis, structure, and properties of metallothioneins, phytochelatins and metal-thiolate complexes. VCH Publishers, New York Stratford IJ, Hoe S, Adams GE, Hardy C, Williamson C (1983) Abnormal radiosensitizing and cytotoxic properties of ortho-substituted nitroimidazoles. Int J Radiat Biol 43 31-43 Stubbe J, Kozarich JW (1987) Mechanisms of bleomycin-induced DNA degradation. Chem Rev 87 1107-1136... 

The electron affinity of 3-(iV-methylpiperazino)-5-nitroindazole, 3,5-dinitroindazole, and molecular complex of the last with water is discussed on the basis of their half-wave potentials and in connection with their eventual radiosensitizing properties [667], The mechanism of EC behavior of 2-substituted 5(6)-nitrobenzimidazoles in acetonitrile has been investigated by classical polarography, cyclic voltammetry, and platinum rotating disk electrode with a ring (RDER) [888,991], It is shown that... 

Their best agent was the cobalt(lll) complex of 5,10-bis(4-methylpyridinium)-15,20-bis-(4-nitrophenyl)porphyrin, which had an SER of 1.22 at 50 pM towards CHO hypoxic cells. This complex was actually the most promising of over 50 studied. Using this CHO tumor cell line and identical XRT conditions (i.e. oxic and hypoxic lOOpM porphyrin concentration 16 Gy), O Hara et al. found that the cobalt(III) complexes, CoTPPS and COTMPyP, exhibited a weak sensitization effect (SER = 1.05-1.22, with or without serum-containing medium). These workers also concluded that the introduction of nitro and/or positively charged substituents on the porphyrin periphery serves to augment the net radiosensitization effect for these kinds of Co(lll) porphyrins [153,154]. Unfortunately, even when enhanced in this way, the net sensitization effect is small. 

Computed chemical shifts (5s H, S N, S Pt, S Ru, S Rh) of transition-metal (M = Zn, Pd, Pt, Ru, Rh) complexes with a prototypical nitro-imidazole-based radiosensitizer, l,2-dimethyl-5-nitro-17/-imidazole, were reported at the GIAO-BP86 and B3LYP levels for BP86/ECP1-optimized geometries <2005HCA2705>. 

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