N-Acetylated Gemini Surfactants: Synthesis, Surface-Active Properties, Antifungal Activity, and Ecotoxicity Bioassays

Laura M. Machuca; Ulises Reno; Silvana C. Plem; Ana María Gagneten; Marcelo C. Murguía

doi:10.4236/aces.2015.52023

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Advances in Chemical Engineering and Science > Vol.5 No.2, April 2015

N-Acetylated Gemini Surfactants: Synthesis, Surface-Active Properties, Antifungal Activity, and Ecotoxicity Bioassays ()

Laura M. Machuca¹, Ulises Reno², Silvana C. Plem¹, Ana María Gagneten², Marcelo C. Murguía^1*

¹Laboratory of Applied Chemistry, Faculty of Biochemistry and Biological Sciences, National University of Litoral, Santa Fe, Argentina.
²Laboratory of Ecotoxicology, Faculty of Humanities and Sciences, National University of Litoral, Santa Fe, Argentina.

DOI: 10.4236/aces.2015.52023 PDF HTML XML 4,140 Downloads 4,885 Views Citations

Abstract

A series of N-acetylated cationic gemini surfactants (3a-e) having dimeric structures derived from tertiary amines were synthesized. Their antifungal potency and surface properties were determined. It also studied the acute toxicity of the molecule with the best performance and the best water solubility (3e) through Chlorella vulgaris and Daphnia magna bioassays. The results were compared to those obtained for a commercially available reference compound 2-(thiocyanomethylthio) benzothiazole (TCMTB). Parameters such as surface tension (ϒCMC), critical micelle concentration (CMC), surface excess concentration (Γ), and area per molecule (A) were determined. The resulting values indicated that the five gemini surfactants are characterized by good surface-active and self-aggregation properties. All surfactants were tested to evaluate their antifungal activity. Six fungal strains were used to conduct the study. The minimum inhibitory concentration (MIC) value was measured by the fungal growth inhibition. The results of the MICs were compared with two commercially available reference compounds (Fluconazole and TCMTB). The least active molecule was 3e, but 3b and 3d were found to be the most potent compounds with a similar activity for all strains. Candida albicans was the most sensitive one. In contrast, Aspergillus niger was resistant. Ecotoxicity of gemini 3e was assessed: the commercial formulation (TCMTB) was between three and four orders of magnitude more toxic than the gemini one for the biological species tested.

Keywords

Gemini Surfactants, Surface-Active Properties, Antifungal Activity, Ecotoxicity Bioassays

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Machuca, L. , Reno, U. , Plem, S. , Gagneten, A. and Murguía, M. (2015) N-Acetylated Gemini Surfactants: Synthesis, Surface-Active Properties, Antifungal Activity, and Ecotoxicity Bioassays. Advances in Chemical Engineering and Science, 5, 215-224. doi: 10.4236/aces.2015.52023.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Orlita, A. (2004) Microbial Biodeterioration of Leather and Its Control: A Review. International Biodeterioration & Biodegradation, 53, 157-163. http://dx.doi.org/10.1016/S0964-8305(03)00089-1
[2]	Abad, M.J., Ansuategui, M. and Bermejo, P. (2007) Active Antifungal Substances from Natural Sources. ARKIVOC, vii, 116-145.
[3]	Menger, F.M. and Keiper, J.S. (2000) Gemini Surfactants. Angewandte Chemie International Edition, 39, 1906-1920. http://dx.doi.org/10.1002/1521-3773(20000602)39:11<1906::AID-ANIE1906>3.0.CO;2-Q
[4]	Zana, R. (2002) Dimeric (Gemini) Surfactants: Effect of the Spacer Group on the Association Behavior in Aqueous Solution. Journal of Colloid and Interface Science, 248, 203-251. http://dx.doi.org/10.1006/jcis.2001.8104
[5]	Zana, R. and Xia, J. (2004) Gemini Surfactants. Surfactant Science Series. Marcel Dekker, New York
[6]	Menger, F.M. and Migulin, V.A. (1999) Synthesis and Properties of Multiarmed Geminis. The Journal of Organic Chemistry, 64, 8916-8921. http://dx.doi.org/10.1021/jo9912350
[7]	Menger, F.M. and Mbadugha, B.N.A. (2001) Gemini Surfactants with a Disaccharide Spacer. Journal of the American Chemical Society, 123, 875-885. http://dx.doi.org/10.1021/ja0033178
[8]	Zhu, Y., Masuyama, A., Kirito, Y., Okahara, M. and Rosen, M.J. (1992) Preparation and Properties of Glycerol Based Double or Triple-Chain Surfactants with Two Hydrophilic Ionic Groups. Journal of the American Oil Chemists Society, 69, 626-632. http://dx.doi.org/10.1007/BF02635800
[9]	Devínsky, F., Lacko, L., Mlynarcik, D., Racansky, V. and Krasnec, L. (1985) Relationship between Critical Micelle Concentration and Minimum Inhibitory Concentrations for Some None-Aromatic Quaternary Ammonium Salts and Amine Oxides. Tenside Detergents, 22, 10-15.
[10]	Murguía, M.C. and Grau, R.J. (2001) Synthesis of New Pentaerythritol-Based Gemini Surfactants. Synlett, 8, 1229- 1232. http://dx.doi.org/10.1055/s-2001-16060
[11]	Murguía, M.C., Vaillard, S.E. and Grau, R.J. (2001) A Facile, Selective Preparation of Monoketals from Pentaerythritol and Ketones. Synthesis, 7, 1093-1097. http://dx.doi.org/10.1055/s-2001-14569
[12]	Murguía, M.C., Cabrera, M.I. and Grau, R.J. (2002) Selective Preparation of Key Intermediates for the Synthesis of Gemini Surfactants by Phase-Transfer Catalysis. Reaction Kinetics and Catalysis Letters, 75, 205-211. http://dx.doi.org/10.1023/A:1015219825198
[13]	Murguía, M.C., Cabrera, M.I., Guastavino, J.F. and Grau, R.J. (2005) New Oligomeric Surfactants with Multiple-Ring Spacers: Synthesis and Tensioactive Properties. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 262, 1-7. http://dx.doi.org/10.1016/j.colsurfa.2005.03.018
[14]	Murguía, M.C., Machuca, L.M., Lurá, M.C., Cabrera, M.I. and Grau, R.J. (2008) Synthesis and Properties of Novel Antifungal Gemini Compound Derived from N-Acetyl Diethanolamines, Journal of Surfactants and Detergents. 11, 223-230. http://dx.doi.org/10.1007/s11743-008-1076-4
[15]	Sánchez, V.G., Giudici, C.J., Bassi, A.R. and Murguía, M.C. (2012) Synthesis, Surface-Active Properties, and Anthelmintic Activities of New Cationic Gemini Surfactants against the Gastrointestinal Nematode, Heligmosomoides polygyrus bakeri, in Vitro. Journal of Surfactants and Detergents, 15, 463-470. http://dx.doi.org/10.1007/s11743-012-1337-0
[16]	Kopecky, F. (1996) Micellization and Other Associations of Amphiphilic Antimicrobial Quaternary Ammonium Salts in Aqueous Solutions. Die Pharmazie, 51, 135-144.
[17]	Dubnicková, M., Pisárcik, M., Lacko, I., Devínsky, F., Mlynarcik, D. and Balgavy, P. (1997) Gemini Amphiphiles: Antimicrobial Activity, Micellization and Interaction with Phospholipid Bilayers. XIIIth School on Biophysics of Membrane Transport, Cellular and Molecular Biology Letters, 2, (Suppl. 1), 215-216.
[18]	Dubnicková, M., Yaradaikin, S., Lacko, I., Devínsky, F., Gordeliy, V. and Balgavy, P. (2004) Effects of Gemini Surfactants on Egg Phosphatidylcholine Bilayers in the Fluid Lamellar Phase. Colloids and Surfaces B: Biointerfaces, 34, 161-164. http://dx.doi.org/10.1016/j.colsurfb.2003.12.009
[19]	Horniak, L., Ebringer, L. and Balgavy, P. (1990) Interaction of Bactericidal Bis-Ammonium Salts with Model and Bacterial Membranes. IUMS Congress: Bacteriology and Mycology, Osaka, 16-22 September 1990, Book of Abstracts, 171.
[20]	Iwamoto, S., Otsuki, M., Sasaki, Y., Ikeda, A. and Kikuchi, J. (2004) Gemini Peptide Lipids with Ditopic Ion-Recognition Site. Preparation and Functions as an Inducer for Assembling of Liposomal Membranes. Tetrahedron, 60, 9841-9847. http://dx.doi.org/10.1016/j.tet.2004.08.072
[21]	Bell, P.C., Bergsma, M., Dolbnya, I.P., Bras, W., Stuart, M.C.A., Rowan, A.E., Feiters, M.C. and Engberts, J.B.F.N. (2003) Transfection Mediated by Gemini Surfactants: Engineered Escape from the Endosomal Compartment. Journal of the American Chemical Society, 125, 1551-1558. http://dx.doi.org/10.1021/ja020707g
[22]	David, S., Pérez, L. and Infante, M.R. (2002) Sequestration of Bacterial Lipopolysaccharide by Bis(Args) Gemini Compounds. Bioorganic & Medicinal Chemistry Letters, 12, 357-360. http://dx.doi.org/10.1016/S0960-894X(01)00749-1
[23]	Diz, M., Manresa, A., Pinazo, A., Erra, P. and Infante, M.R. (1994) Synthesis, Surface Active Properties and Antimicrobial Activity of New Bis Quaternary Ammonium Compounds. Journal of the Chemical Society, Perkin Transactions, 2, 1871-1876. http://dx.doi.org/10.1039/p29940001871
[24]	Okazaki, K., Maeda, T., Nagamune, H., Manabe, Y. and Kourai, H. (1997) Synthesis and Antimicrobial Characteristics of 4,4’-(α,ω-Polymethylenedithio)bis(1-alkylpyridinium iodide)s. Chemical and Pharmaceutical Bulletin, 45, 1970- 1974.
[25]	Maeda, T., Manabe, Y., Yamamoto, M., Yoshida, M., Okazaki, K. and Nagamune, H. (1999) Synthesis and Anti- microbial Characteristics of Novel Biocides, 4,4’-(1,6-Hexamethylenedioxy dicarbonyl)bis(1-alkylpyridinium iodide)s. Chemical and Pharmaceutical Bulletin, 47, 1020-1023.
[26]	Iyer, S.S., Rele, S.M., Baskaran, S. and Chaikof, E.I. (2003) Design and Synthesis of Hyaluronan-Mimetic Gemini Disaccharides. Tetrahedron, 59, 631-638. http://dx.doi.org/10.1016/S0040-4020(02)01567-3
[27]	Shirai, A., Maeda, T., Nagamune, H., Matsuki, H., Kaneshina, S. and Kourai, H. (2005) Biological and Physicochemical Properties of Gemini Quaternary Ammonium Compounds in Which the Positions of a Cross-Linking Sulfur in the Spacer Differ. European Journal of Medicinal Chemistry, 40, 113-123. http://dx.doi.org/10.1016/j.ejmech.2004.09.015
[28]	Chaudier, Y., Zito, F., Barthélémy, P., Stroebel, D., Améduri, B., Popot, J.L. and Pucci, B. (2002) Synthesis and Preliminary Biochemical Assessment of Ethyl-Terminated Perfluoroalkylamine Oxide Surfactants. Bioorganic & Medicinal Chemistry Letters, 12, 1587-1590. http://dx.doi.org/10.1016/S0960-894X(02)00242-1
[29]	Massi, L., Guittard, F., Géribaldi, S., Levy, R. and Duccini, Y. (2003) Antimicrobial Properties of Highly Fluorinated Bis-Ammonium Salts. International Journal of Antimicrobial Agents, 21, 20-26. http://dx.doi.org/10.1016/S0924-8579(02)00271-6
[30]	Massi, L., Guittard, F. and Géribaldi, S. (2000) Application en Tant que Biocides des Composés QUATERFLUO®. MC Patent No. 2452.
[31]	Tewari, N., Tiwari, W.K., Tripathi, R.P., Chaturvedi, V., Srivastava, A., Srivastava, R., Shukla, P.K., Chaturvedi, A.K., Gaikwad, A., Sinha, A. and Srivastava, B.S. (2004) Synthesis of Galactopyranosyl Amino Alcohols as New Class of Antitubercular and Antifungal Agents. Bioorganic Medicinal Chemistry Letters, 14, 329-332. http://dx.doi.org/10.1016/j.bmcl.2003.11.020
[32]	Botana López, L., Landoni, M.F. and Martin Jiménez, T. (2002) Farmacología Terapéutica Veterinaria. McGraw-Hill International, Madrid.
[33]	European Commission (2005) Institute for Health and Consumer Protection. European Chemicals Bureau I-21020 Ispra (VA) Italy. Summary Risk Assessment Report. ALKANES, C14-17, CHLORO (MCCP) Part I-Environment. CAS No. 85535-85-9. EINECS No. 287-477-0 SUMMARY RISK ASSESSMENT REPORT. Final Report, The United Kingdom Rapporteur.
[34]	Meneses, E.S., Arguelho, M.L.P. and Alves, J.P.H. (2005) Electroreduction of the Antifouling Agent TCMTB and Its Electroanalytical Determination in Tannery Wastewaters. Talanta, 67, 682-685. http://dx.doi.org/10.1016/j.talanta.2005.01.058
[35]	Vogel, A.I. (1989) Vogel’s Textbook of Practical Organic Chemistry. 5th Edition, John Wiley & Sons, Inc., New York.
[36]	Chlebicki, J., Wegrzyńska, J., Maliszewska, I. and Oswiecimska, M. (2005) Preparation, Surface-Active Properties, and Antimicrobial Activities of Bis-Quaternary Ammonium Salts from Amines and Epichlorhidrin. Journal of Surfactants and Detergents, 8, 227-232. http://dx.doi.org/10.1007/s11743-005-0350-6
[37]	National Committee for Clinical Laboratory Standards (2002) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. M27-A2. NCCLS, Wayne.
[38]	National Committee for Clinical Laboratory Standards (2002) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. M38-A. NCCLS, Wayne.
[39]	Sager, R. and Granik, S. (1953) Nutritional Studies with Chlamydomonas Reinhardti. Annals of the New York Academy of Sciences, 56, 831-838. http://dx.doi.org/10.1111/j.1749-6632.1953.tb30261.x
[40]	USEPA (2002) Short Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to Fresh Water Organism. 4th Edition, EPA-821-R-02-013, Washington DC.
[41]	Reno, U., Gutierrez, M.F., Regaldo, L. and Gagneten, A.M. (2014) The Impact of Eskoba®, a Glyphosate Formulation, on the Freshwater Plankton Community. Water Environment Research, 86, 2294-2300. http://dx.doi.org/10.2175/106143014X13896437493580
[42]	American Public Health Association (APHA) (1998) Standard Methods for the Examination of Water and Wastewater. 21st Edition, APHA, Ap 8010G, Washington DC, 8-20, 8-23.
[43]	Ronco, A., Díaz Báez, M.C. and Pica Granado, Y. (2003) Ensayos Toxicológicos y Métodos de Evaluación de Calidad de Aguas. Estarandización, Intecalibración, Resultados y Aplicaciones. 47-52.
[44]	US Environmental Protection Agency (2002) Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms. EPA-821/R-02-012, Washington DC.
[45]	Finney, D.J. (1971) Probit Analysis. Cambridge University Press, Cambridge, 333.
[46]	Lofrano, G., Belgiorno, V., Gallo, M., Raimo, A. and Meric, S. (2006) Toxicity Reduction in Leather Tanning Wastewater by Improved Coagulation Flocculation Process. Global NEST Journal, 8, 151-158.
[47]	Terra, N.R., Feiden, I.R., Lucheta, F., Goncalves, S.P. and Gularte, J.S. (2010) Bioassay Using Daphnia magna Straus, 1820 to Evaluate the Sediment of Caí River (Rio Grande do Sul, Brasil). Acta Limnologica Brasiliensia, 22, 442-454. http://dx.doi.org/10.4322/actalb.2011.008
[48]	Guilhermino, L., Diamantino, T., Silva, M.C. and Soares, A.M.V.M. (2000) Acute Toxicity Test with Daphnia magna: An Alternative to Mammals in the Prescreening of Chemical Toxicity. Ecotoxicology and Environmental Safety, 46, 357-362. http://dx.doi.org/10.1006/eesa.2000.1916
[49]	Machuca, L.M., Lurá, M.C. and Murguía, M.C. (2011) Moléculas anfipáticas de la familia gemini. Argentina Patente Acta No. P20130103027.