Chelation Polymers

Numerous iron-containing polymers have been synthesized and studied for biomedical application. Here we will look at simple iron(II) chelating polymers developed for medical applications. 

Research in the chelation of iron is sponsored by various Cooley s Anemia Fmmdations, the National Institute of Arthritis, Diabetes, and Digestive, and Kidney Diseases of the National Institutes of Health. Much of effort has been directly toward mimicking the naturally occurring siderophores such as desferrioxamine by inclusion of hydroxamic acids, catechols, and phenols into a variety of structures. This gives compoimds that have vary high stability constants for iron but are nontoxic and active in the human body. 

Winston and coworkers did extensive work in this area to develop polymer-containing materials that bind iron. These studies illustrate the formation of metal-containing materials, not as a drug itself, but to study the effectiveness of the chelating agent as a potential drug for biomedical use. 

Hydroxamic acid is the fimctional group responsible for binding the iron in DFO. It has been known since 1869. The first hydroxamic acid polymer was made in 1946. A number of hydroxamic acid polymers with controlled spacing have been developed that effectively bind iron with iron binding log K values around 30. The structure of one of these is given below, where R] is the spacer. 

Carraher and coworkers have synthesized a number of group VA-containing polymers that exhibit both anti-tumor and anti-bacterial actively. Polymers formed from reaction with triphenylantimony dichloride and thiopyrimidine exhibit good inhibition of Balb/3T3 cells at concentrations down to 10 pg/mL. 

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Platinum-group metals (qv) form complexes with chelating polymers with various 8-mercaptoquinoline [491-33-8] derivatives (83) (see Chelating agents). Hydroxy-substituted quinolines have been incorporated in phenol—formaldehyde resins (84). Stannic chloride catalyzes the condensation of bis(chloromethyl)benzene with quinoline (85). 

Soluble Metal Chelate Polymers of Coordination Numbers 6, 7, and 8... 

ARCHER ETAL. Soluble Metal Chelate Polymers... 

Figure 9.54 The iodoacetamide derivative of DPA has been used to create a chelating polymer of lanthanide metals using poly-L-lysine as the backbone.

Slinkin, M.A., Klibanov, A.L., and Torchilin, V.P. (1991) Terminal-modified polylysine-based chelating polymers Highly efficient coupling to antibody with minimal loss in immunoreactivity. Bioconjugate Chem. 2, 342-348. 

Trubetskoy, V.S., Narula, J., Khaw, B.A., and Torchilin, V.P. (1993) Chemically optimized antimyosin Fab conjugates with chelating polymers Importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization. Bioconjugate Chem. 4, 251-255. 

Figure 2 Chemistry of the polymeric chelates used for loading liposomes and micelles with multiple reporter metal atoms, (a) Synthesis of a single terminus-PDP-activated chelating polymer (DTPA-polylysine) starting from CBZ-protected polylysine and SPDR...

Torchilin, V. P., and Klibanov, A. L. The antibody-linked chelating polymers for nuclear therapy and diagnostics. CRC Crit. Rev. Then Drug Carriers Syst. 1991, 7, 275-308. 

Note 1 Chelating polymers mostly act as ion-exchange polymers specific to metal ions that form chelates with chelating ligands of the polymer. 

Molybdenum peroxide immobilized by coordination of a chelating polymer Diaion CR-20. 

Chelating polymers must be developed and evaluated according to the type of waste being treated. Because some contaminants may be present in relatively low concentrations with respect to other ions in waste solutions, polymers that have high binding and selectivity for the particular contaminant must be developed. 

H. P. Gregor K. W. Pepper L. R. Morris Invention and development of chelating polymers. 1952-1971... 

Template Polymers. Template effects in chelating polymers constitute an interesting development in the field of metal containing polymers. The Template effects are interpreted by the fact that the small molecule is templating a pattern in the macromolecule which can be recognized by the same molecule in a subsequent process. The idea is to prepare a polymer from the metal-chelated monomer, to remove the metal ion, and then to measure the selectivity of the prepared polymer for the metal ion of the template [36]. Typical examples of template systems are 4-vinyl-4 -methylbipyridine (Neckers [36]) and 1-vinyl-imidazole (Tsuchida [37]). These are polymerized in presence of divinylbenzene [36] and appropriate metal salts (Co2+, Cu2+, Ni2+, Zn2+). The template metal ions are removed by acid leaching and the polymer subsequently used for metal ion absorption studies (Fig. 16). 

Muzzarelli R. A. A. Natural Chelating Polymers. Oxford Pergamon Press, 1973. 254 p. 

We have synthesized and tested an example boron-chelating polymer based on a commercially available dendrimeric poly(amido amine) (PAMAM). Dendrimeric chelants offer several advantages over polymers typically used in PAUF. Foremost among these is the reduced viscosity of dendrimer solutions as compared to solutions of linear polymers[6]. This allows the use of higher polymer concentrations than previously feasible (though in the present study we worked at polymer concentrations of less than 5% due to the expense of the starting dendrimer). In this study, the dendrimeric chelant also serves as a convenient, monodisperse polymer with which to test the mathematical model for boron speciation which is derived from the work of Wise and Weber[l],... 

Polymerizable indazole derivatives have received some attention with respect to the preparation of redox polymers and metal ion chelating polymers (73MI11102). Monomers such as 3-vinyl-4,7-dihydro-1//-4,7-indazoledione (63) are readily prepared by 1,3-dipolar cycloaddition of vinyldiazomethane to 1,4-benzoquinones. Crosslinked, low swelling, recyclable redox polymers have been prepared from these monomers. 

Biological significance can sometimes arise in rather unexpected ways the thermal properties of chelate polymers of 2,6-diaminopimelic acid (dap 12) and 4,4 -diamino-3,3 -dicarboxybiphenyl (bbdc 13) with Zn11 have been compared241 with those of non-polymeric divalent metal chelates with amino acids. This confirms the expected enhancement of thermal stability when coordination polymerization occurs, these results possibly being relevant to the thermal stability of certain bacterial spores which contain dap. Zn11 complexes of dap are more thermally stable than those of bbdc, possibly because the latter chelate cannot pack as well, due to the intermolecular repulsions of the biphenyl groups. 

Platinum-group metals form complexes with chelating polymers with various 8-mercaptoquinoline derivatives. 

New chelating polymers having high adsorption ability for uranium have been given much attention with respect to recovery and purification of uranium. The polymers having hydroxamic acid (24), amidoxime (25), dihydroxyphospino, or... 

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