ISSN 1070-4272, Russian Journal of Applied Chemistry, 2016, Vol. 89, No. 1, pp. 160−164. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.I. Vorob’eva, M.S. Babaev, L.V. Spirikhin, N.M. Shishlov, S.V. Kolesov, 2016, published in Zhurnal Prikladnoi Khimii, 2016, Vol. 89,
No. 1, pp. 134−139.
AND POLYMERIC MATERIALS
Copolymer of N,N-Diallyl-N,N-dimethylammonium Chloride
with Maleic Acid As Drug Carrier
A. I. Vorob’eva, M. S. Babaev, L. V. Spirikhin, N. M. Shishlov, and S. V. Kolesov
Ufa Institute of Chemistry, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, Bashkortostan, 450054 Russia
Received August 28, 2015
Abstract—A copolymer of N,N-diallyl-N,N-dimethylammonium chloride with maleic acid of constant composition
was prepared under the conditions of radical initiation. The possibility of the functionalization of the copolymer
with drugs containing amino groups by polymer-analogous transformations was examined. Conditions were
found for preparing conjugates of the copolymer with isoniazid. The structures and the quantitative compositions
of the conjugates were determined by
С NMR spectroscopy, and the possibility of preparing conjugates with
controlled drug content was demonstrated.
Biologically active polymers are widely used in vari-
ous branches of medicine and molecular biology [1–4].
Synthetic cationic polyelectrolytes (CPEs) exhibiting
antimicrobial activity are very interesting and prom-
ising for use in medicine [5, 6]. Owing to their easy
adsorption on negatively charged cell membranes and
membranotropic action, high local concentration of the
antimicrobial agent on the cell surface is created, and
the membrane permeability increases . By interact-
ing with cell membranes, CPEs inﬂ uence their function-
ing, enhancing the drug transport to the cell; they also
inhibit bacterial enzymes. CPEs based on N,N-diallyl-
dimethylammonium chloride (AMAC) are of particular
interest for medicine. They are nontoxic, contain reac-
tive groups, and can act as polymeric drug carriers, pro-
longing the action of drugs and reducing their toxicity.
In particular, functionalization of AMAC–sulfur diox-
ide copolymer with drugs containing СООН groups
by replacement of the chloride ion by the –СООR ion
of drug has been reported . The method allows im-
mobilization on a polymer matrix of such antimicrobial
agents as acetylsalicylic acid, benzylpenicillin, and 4-
and 5-aminosalicylic acids, which exhibit antitubercular
and ulcer-healing activity, and of other drugs containing
Copolymers of AMAC with maleic acid (MA) show
much promise in the development of new water-soluble
physiologically active drug forms of prolonged action
by functionalization of macromolecular compounds
with drugs. Synthesis of such copolymers has been stud-
ied in detail .
A previously made study of the acute toxicity  re-
vealed no signs of intoxication on introducing AMAC–
MA copolymer into the mouse stomach in an amount
of up to 5000 mg kg
. Larger doses were not tested be-
cause of no apparent toxic effect of the copolymer.
Studies of the antimicrobial activity (by the method
of “diffusion into agar” and twofold serial dilutions in
culture broth) have shown that the copolymer exhibits
antibacterial activity toward all the microorganisms
used (E. coli, B. anthracoides, St. aureus, Citrobacter
spp., Klebsiellae spp., Ps.aeruginosa, Shigellae spp.,
Vibrion, S. marcesncens). The minimal suppressing
concentration of the copolymers is 1.2–1.5 mg mL
The above data show that the copolymer of N,N-diallyl-
N,N-dimethylammonium chloride with maleic acid is
nontoxic (hazard class IV), exhibits pronounced bacte-
ricidal activity, and is potentially suitable for producing
drug forms of prolonged action.