Diazo coupling of catecholamines with poly(organophosphazenes)

Abstract

Polymer-bound catecholamines have been prepared by the diazotization of high-polymeric [NP(OC6H5)z(OC6H4NH2-p)),]n, followed by coupling to dopamine, dZ-epinephrine, and dZ-norepinephrine.These reactions were preceded by model compound studies with the cyclic trimer N3P3(OC6H5)5OC6H4NH2. In both cases, the aminophenoxy units were generated by reduction of 4-nitrophenoxy groups with Pt02 and hydrogen. The phosphazene skeleton was unaffected by the reduction, diazotization, and diazo coupling processes. The physical characteristics of the trimers and high polymers are described. The polymeric azocatecholamine derivatives were purified by gel permeation chromatography, which reduced contamination by the unbound catecholamine to undetectable levels. The polymeric derivatives were found to elicit inhibition of prolactin release from rat pituitary cells in culture for 48 h.Considerable interest exists in the synthesis of biologically active polymers.1-4 One aspect involves the attachment of biologically active small molecules to polymers in order to confer, for example, chemotherapeutic activity on the macromolecules5-7 themselves or to generate a controlled-release system for the active small molecule. Thus, the synthesis of macromolecules that can function as carrier species for small-molecule chemotherapeutic agents or that can selectively bind ions in aqueous media is a subject of growing importance. So, too, is the preparation of polymers that may serve as templates and supports for the covalent binding of catecholamines.The pioneering studies by MacLeod8,9 showed that dopamine reduces prolactin secretion from the rat anterior pituitary gland in vitro in a dose-dependent and pharmacologically reversible manner. It is now well established that this inhibitory effect by dopamine is specifically mediated via receptors on the membrane of the cell that produces prolactin.10The linkage of dopamine and other catecholamines to a synthetic polymer is expected to open up a number of possibilities for new research into the mechanism of action of neurotransmitters. First, the use of such polymeric species in affinity chromatography is an important prospect. Second, the availability of a polymer-immobilized dopamine allows the study of cell response mechanisms under conditions where membrane-penetrating neurotransmitter dopamine molecules can be excluded from entering the cell. Third, polymer-bound dopamine is expected to be more stable to chemical degradation than the free active molecule. Fourth, depending on the site of linkage of the catecholamine to the polymer, it may be

Expanding Options in Polyphosphazene Biomedical Research

“…5. Secondary substitution reactions carried out on the organic side groups introduced by one of the preceding methods [37][38][39][40][41][42].…”

“…Secondary substitution reactions carried out on the organic side groups introduced by one of the preceding methods. Organic side groups incorporated into a polyphosphazene by one of the preceding methods can themselves be modified by exposure to reagents that introduce additional functionality [37][38][39][40][41][42]. For example, aryloxy side groups can be sulfonated or nitrated, ester groups can be hydrolyzed to carboxylic acid units, aryloxy groups with chloro or bromo substituents can be lithiated and phosphonated, transition metals can be coordinated with the existing side chains, alkyl groups can be used for crosslinking, and so on.…”

“…3. Linkage of bioactive molecules to polyphosphazene surfaces [86][87][88][89]. Proteins have been immobilized on polyphosphazene surfaces via reactions with -CH 2 Br units on phenoxy side groups.…”

Polyphosphazenes with etheric side groups: prospective biomedical and solid electrolyte polymers

“…This is a consequence of the substitutive mode of synthesis used for these polymers, as described in a number of earlier publications. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The method involves the prior synthesis of a reactive, high polymeric poly(dihalophosphazene) intermediate, such as 1, by a ring-opening polymerization of the corresponding cyclic trimer, followed by replacement of the halogen atoms by one or more of a wide variety of organic or organometallic nucleophiles.…”

Organometallic and Bioactive Cyclophosphazenes, and the Relationship to Inorganic Macromolecules

“…These couple with catecholamines such as dopamine to yield a polymer which, in the solid state (15), shows a surface bioogical activity toward rat pituitary cells in culture similar to that found for free dopamine in solution. 18 This, then, is a prototype for devices in which biological responses are obtained without release of the small molecule bioagent into the living organism.…”