Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
1998-11-19
2001-03-13
Nutter, Nathan M. (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Polymers from only ethylenic monomers or processes of...
C548S518000
Reexamination Certificate
active
06201086
ABSTRACT:
Conjugated polymers, such as polypyrroles, polythiophenes, polyanilines, polyphenylenes and derivatives thereof are known for their electroactive nature, which is widely described in review works such as the “Handbook of Organic Conducting Polymers” (T. J. Skotheim Editor, Marcel Dekker, New York, 1986). These polymers are obtained in the form of a film on an electrode, in the form of self-supporting films or alternatively in the form of a composite when combined with a polycationic or polyanionic polymer and behave like organic electrodes, which charge up according to an anodic oxidation process, by insertion of ions from the electrolytic medium. This electrochemical process is reversible, the reduction leading to the expulsion of the ions from this conjugated polymer or from the electroactive composite.
A second generation of conjugated polymers was then described in the literature, obtained by the covalent grafting, on to the monomer units of the polymers, of functional groups capable of providing these electroactive conjugated polymers with an additional function. By way of example, electrocatalytic metal complexes were grafted on to the monomer units of the polypyrrole, specific complexing macrocycles were grafted on to the polypyrrole or polythiophene chains for the recognition of cations in an electrolytic medium, and chiral groups were grafted on to polythiophenes for the recognition of optically active anions. All of these routes of functionalization have also formed the subject of development procedures detailed in the literature (F. Garnier, Angew. Chemie, 1989, 101, 529; A. Deronzier, J. C. Moutet, Acc. Chem. Res. 1989, 22, 249; J. Roncali, Chem Rev., 1992, 92, 711).
In the last few years authors have become interested in the use of functionalized conductive polymers for the development of analyte scavengers, in particular for diagnostic purposes. However, as indicated in patent application EP0,314,009, it was commonly accepted by the scientific community that pyrrole polymers substituted either on the nitrogen atom or directly on the carbon atoms of the pyrrole ring were not good candidates for the development of analyte scavengers, in particular on account of the loss of conductivity of said polymers when functional groups are introduced on to the heteroatomic ring. In order to overcome this problem, the authors of this patent application thus envisaged the use of 2,5-di(2-thienylpyrrole) polymers which were grafted in the 3-position of the pyrrole ring with a reactive moiety with which an organic molecule could become covalently bonded. It should, however, be noted that on account of the hydrophobicity of the thiophene rings, the polymers described cannot be conductive and electroactive in aqueous media and consequently do not appear to be suitable for the detection and/or characterization of an analyte in a biological sample (see J. Roncali et al., Chem. Comm., 1986, page 783 and G. Tourillon et al., Electronal. Chem., 161, 407, 1984).
It has now been discovered, entirely surprisingly and contrary to what was hitherto accepted by specialists, that the conductivity and electroactivity of polypyrroles are retained provided that a functional group is grafted in the 3- or 4-position on the pyrrole ring using a functionalizing agent which allows the intended function to be distanced from the pyrrole ring. An antiligand is covalently bonded to the free end of the functional group, without the abovementioned properties of the polymer being modified. Such functionalized polymers have to date never been described and have shown themselves to be entirely suitable as scavengers for a biological ligand. Moreover, polypyrroles prove to be advantageous polymers on account of their biocompatibility. Lastly, the polypyrroles thus functionalized make it possible to prepare electroactive and conductive polymers of considerable thickness (up to several millimeters thick), which thereby allows a great density of functional sites and proportionately improves the sensitivity.
The subject of the invention is thus an electrically conductive electroactive functionalized polymer which corresponds to the formula (I):
in which:
n is a non-zero integer and i is an integer ranging from 2 to n−1, and
R1, Ri and Rn, which may be identical or different, each represent H or a functional group capable of covalently bonding with a first biological molecule or antiligand, and in that said polymer has a conductivity and an electroactivity which are substantially of the same order as that of the corresponding non-functionalized conjugated polymer, that is to say of the corresponding polymer of formula I, in which R1, Ri and Rn each represent H.
More particularly, the functional group(s) is(are) independently chosen from the following set of functional groups:
Y
p
—C—X where X represents H, OH, a substituted or unsubstituted lower O-alkyl radical, or a halogen, in particular Cl; Yp—NHZ, Z representing H or an alkyl radical; Y
p
—NH—CO—CF
3
; Y
p
—X where X corresponds to the above definition, p being an integer preferably equal to 0, 1 or 2; —Si(alkyl)
3
, —Si(alkoxyl)
3
or an activated ester group such as COON-hydroxysuccinimide.
Y preferably represents a group chosen from alkyls having from 1 to 5 carbon atoms, alkoxyls having from 1 to 5 carbon atoms and polyethers corresponding to the general formula (CH2—CH2—O)m—(CH2)m′—, m representing an integer ranging from 1 to 3 and m′ an integer equal to 1 or 2.
The invention also concerns an electrically conductive, electroactive functionalized conjugated polymer of formula (I′)
wherein
n is an integer or zero,
each R, which may be identical or different from one monomer unit to one another, is selected from the group consisting of H and functional groups capable of covalently bonding with a first biological molecule or antiligand with the proviso that (a) at least one said R of formula (I′) represents said functional group or (b) is each Y
p
R in formula (I′) is identical, they are different from CH
2
—COOH,
each Y
p
, which may be identical or different from one monomer unit to one another, is a coupling arm wherein p is zero or an integer,
wherein said polymer has a conductivity and an electroactivity which are substantially of the same order as a conductivity and an electroactivity of a corresponding polymer of formula (III), in which each said R represents H.
Preferably, p is 0, 1 or 2
Preferred polymers of formula (I′) are the following:
polymers wherein R is selected from the group consisting of COX, where X represents H, OH, a substituted or unsubstituted lower O-alkyl radical or an halogen; activated esters; NHZ where Z represents H, an alkyl radical or CO—CF
3
; Si(alkyl)
3
; Si(alkoxyl)
3
; electrochemical probes; electrochemical probes bound to an activated ester; electrochemical probes are preferably selected from the group consisting of ferrocene and quinone and/or activated esters are selected from the group consisting of COON-hydroxysuccinimide, COON-hydroxyphtalimide, and COOpentafluorophenol; the halogen is preferably chlorine;
polymers wherein p is at least one and R is selected from the group consisting of H, OH, a substituted lower O-alkyl radical, and a halogen;
polymers wherein Y is selected from the group consisting of alkylene groups having from 1 to 5 carbon atoms; oxy-alkylene groups having from 1 to 5 carbon atoms; polyethers having the formula [(CH
2
—CH
2
—O)
m
(CH
2
)
m
′] where m is an integer ranging from 1 to 3 and m′ is an integer equal to 1 or 2; (CH
2
)
m
CONH(CH
2
)
m″
where each of m and m″ identical or different is an integer ranging from 1 to 3; (CH
2
)
m
CON(CH
2
)
m″′
where m is an integer ranging from 1 to 3 and m″′ is 2 or 3;
Said antiligand is able to form an antiligand/target molecule complex. Preferably, said complex is selected from the group consisting of peptide/antibody, antibody/haptene, hormone/receptor, polynucleotide hybrids/polynucleotide and polynucleotide
ucleic acid couple.
The target molecu
Bio Merieux
Nutter Nathan M.
Oliff & Berridg,e PLC
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