Synthesis and antimicrobial properties of polymerizable quaternary ammoniums

doi:10.1016/j.ejmech.2009.03.031

European Journal of Medicinal Chemistry

Volume 44, Issue 8, August 2009, Pages 3201-3208

https://doi.org/10.1016/j.ejmech.2009.03.031 Get rights and content

Abstract

Introduction of biocide monomers during the process of polymerization is a promising approach in the development of new permanent non leaching biocide materials. Two series of surfactants monomers, with a quaternary ammonium group as polar head and an acrylic function as the polymerizable moiety, were synthesized and tested to evaluate their surface active properties alongside with their antibacterial and antifungal properties. Four microbial strains were used to perform the study: Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus niger. The biocidal efficacy measured by bacterial and fungal growth inhibition expressed as MIC (Minimal Inhibitory Concentration) and MLC (Minimal Lethal Concentration) values was discussed as a function of molecular parameters. All the synthesized surfactant monomers presented bactericidal and fungicidal activities. Increasing the spacer between the acrylic part and the ammonium group has a favourable effect on the MIC and MLC results.

Graphical abstract

Quaternary ammonium acrylates, usable as precursor of bioactive materials, were prepared and their biocidal activity was evaluated vs. S. aureus, P. aeruginosa, A. niger and C. albicans.

Introduction

The battle against nosocomial infections such as, among others, surgical infections, remains one of the major actual challenges of the hospital. If cautions are numerous to avoid any pollution of inert surfaces (catheters, implants, medical equipments, floors…), the phenomena of resistance developed by the most part of pathogenic organisms require, on one hand, the elaboration of new biocide agents and, on the other hand, completion of long-term bactericidal treatments of surfaces or, in an ideal case, a permanent biocide effect of the surfaces without releasing of the antimicrobial active agents. The implementation of biocide polymeric coatings with a permanent effect introduces not negligible advantages: a non release of antibacterial agents in the surrounding environment and, consequently, a reduction of the resistance phenomena with an attenuation of the development of multi resistant germs [1]. As compared with conventional antibacterial agents of low molecular weight, polymeric antibacterial agents have also the advantages to be non volatizable, chemically stable and hard to permeate through the skin. Moreover, increased efficiency, selectivity, and handling safety are additional benefits.

In the field of disinfection, quaternary ammonium surfactants (QAS) are well-known effective antimicrobial agents and are used in a number of domains such as cosmetics, common antiseptics, sanitizers in hospitals and disinfectants for contact lenses [2]. The efficacy of such agents is conditioned by the amphiphilic nature of the molecule [3] and consequently by its surfactant properties [4]. These products possess properties such as reduction of surface tension and a ready attraction for negatively charged surfaces like bacteria. These characteristics promote their adsorption onto bacteria surfaces. Although, the mode of action cannot be reduced to surface activity only, a cytolytic damage is the primary lesion caused by such cationic surfactants and a major contribution to the cell death. Consequently, there is a well-established relationship between cytolytic action and surface tension [5].

In the perspective to elaborate biocide polymeric materials, we therefore chose to synthesize quaternary ammonium surfactants with an additional polymerizable acrylic moiety. The synthesized compounds are represented Fig. 1.

Some of this kind of compounds has already been described in literature for their surfactant properties [6], [7], [8].

Indeed, surfmers (for SURFactant monoMERS) have been extensively studied [9], [10], [11], [12], [13], [14] because their reactive functionalities give to these surfactants the potentiality to control overall material properties as they polymerize into the bulk polymer network [15], [16]. They can be charged easily for the incorporation of proper biological ligand [17], [18] and controllable drug release [19] or they can serve as carrier for gene delivery [20], [21].

However, to our knowledge, the antibacterial activity of such fundamental precursors has not been investigated. So in this paper, we report on the synthesis of two series of quaternary ammonium monomers and discuss the chemical–biological relationships, mainly the bond between molecular structure and biological activity as precursor of bioactive materials.

Section snippets

Chemistry

Because of the poor solubility of quaternary ammonium compounds in common organic solvents, the strategy to get ammonium compounds is to introduce the quaternary nitrogen as far as possible along the synthesis. Moreover, this minimizes the need of difficult manipulations due to the surfactant nature of the compounds and simplifies many isolation and purification problems [22], [23]. Our general synthetic pathway is described in Scheme1.

The molecules were coded H·m·n where m is the number of

General

Confirmation of the structures of the intermediates and products was obtained by nuclear magnetic resonance (NMR), mass spectrometry (MS) and infrared spectroscopy (FT IR). NMR spectroscopy was carried out using a Bruker Advance 200 MHz or 500 spectrometer. MS was carried out using a Finnigan Matt TSQ 7000 mass spectrometer coupled with a gas chromatograph or liquid chromatography interface. Infrared spectroscopy was carried out using a Perkin Elmer Paragon 1000 FT IR spectrometer. Gas phase

Conclusion

The variation of the surface active properties and the biological activities of ten quaternary ammonium acrylic surfactants, differing in the nature of the hydrocarbon side chain (C₁₀H₂₁, C₁₂H₂₅, C₁₄H₂₉, C₁₆H₃₃ or C₆H₅–CH₂) and the spacer linking the ammonium head to the acrylic moiety (ethyl or undecenyl) were measured. The structure/activity study has shown that the length of the hydrocarbon spacer plays an important role in the biological activity because of its influence on the general

Acknowledgment

The authors wish to thank Catherine Piccini from Rohm and Haas for her valuable collaboration. LC thanks French government for MENRT grant.

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Original articleSynthesis and antimicrobial properties of polymerizable quaternary ammoniums

Abstract

Graphical abstract

Introduction

Section snippets

Chemistry

General

Conclusion

Acknowledgment

Langmuir

Chem. Mater.

Polym. Adv. Technol.

Polymer

Langmuir

Tenside Detergents

J. Med. Chem.

Adv. Colloid Interface Sci.

J. Antimicrob. Chemother.

J. Appl. Microbiol.

J. Appl. Microbiol.

J. Appl. Microbiol.

J. Hosp. Infect.

Handbook of Disinfectants and Antiseptics

Dtsh. Med. Wochenschr.

Pharmazie

Langmuir

Polymer

J. Polym. Sci. Polym. Chem.

Surfactants and Polymers in Aqueous Solution

Original article
Synthesis and antimicrobial properties of polymerizable quaternary ammoniums