Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 939 word(s) 939 2021-09-28 10:25:29 |
2 format correct + 2 word(s) 941 2022-01-28 09:42:04 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Szulc, A. Antimicrobial Activity of Gemini Surfactants. Encyclopedia. Available online: (accessed on 15 April 2024).
Szulc A. Antimicrobial Activity of Gemini Surfactants. Encyclopedia. Available at: Accessed April 15, 2024.
Szulc, Adrianna. "Antimicrobial Activity of Gemini Surfactants" Encyclopedia, (accessed April 15, 2024).
Szulc, A. (2021, November 03). Antimicrobial Activity of Gemini Surfactants. In Encyclopedia.
Szulc, Adrianna. "Antimicrobial Activity of Gemini Surfactants." Encyclopedia. Web. 03 November, 2021.
Antimicrobial Activity of Gemini Surfactants

Gemini cationic surfactants (GS) are constructed from two alkylammonium monomeric salts linked by a spacer.They exhibit significant surface, aggregation and antimicrobial properties. Due to the fact that, in order to achieve the desired utility effect, the minimal concentration of compounds are used, they are in line with the principle of greenolution (green evolution) in chemistry. The obtained results indicate that the synthesized compounds are effective microbicides with a broad spectrum of biocidal activity and are active against Escherichia coli, Staphylococcus aureus, yeast Candida albicans, molds Aspergillus niger and Penicillium chrysogenum. These compounds constitute a new, interesting class of microbicides with a broad spectrum of biocidal activity.

gemini surfactants antimicrobial activity MIC surface activity

1. Introduction

The most important and rapid developing group of antimicrobials includes the quaternary ammonium compounds (QAC).[1] Their effectiveness has been proven over the past century, and various new generations have been introduced since then.[2][3] In the second half of the twentieth century, double quaternary ammonium salts were obtained, and named gemini surfactants (GS) by Menger in 1991.[4] Since then, this class of compounds has been very intensively developed.

These compounds are constructed from two single alkylammonium monomeric salts linked by a connector (spacer). The spacer can be a flexible chain (i.e. polymethylene) or rigid molecule, such as benzene. The linker can also be functionalized by electron-rich atoms, such as oxygen or nitrogen. The substituent is most often a hydrocarbon chain or it can be functionalized by different organic functional groups. The complement to the structure of GS, which ensures the neutral charge of the molecule, is a counter ion.[5][6][7][8][9] The possibility of modifying the structure within the linker, substituents, counter ion, or the cation environment makes it possible to design the structure of the compound so that it exhibits the desired utility properties.

The presence of two cations in the molecule causes gemini surfactants to possess several times better properties than their monomeric counterparts.[10][11][12] They are also known for their broad spectrum of action against bacteria,[13][14] fungi,[15][16] and algae.[17] QAC are significant antiviral compounds[18][19][20]; therefore, it can be assumed that the effectiveness of gemini surfactants against viruses will also be high. The unique antimicrobial activity of gemini surfactants can be explained by the mechanism of biocidal action, which consists in adsorption of cations on the surface of the microorganism and penetration by long alkyl substituents of the cell membrane. This results in damage and outflow of the cytoplasm along with potassium ions and other cellular components, resulting in the death of the microbial cell.[21][22][23] Gemini surfactants are named as multifunctional because they also show high aggregation, surface, and anticorrosive activity.[24][25][26] Moreover, compared to QAC, they are less toxic with respect to aquatic organisms.[27][28] Gemini surfactants have one more unique features that makes them superior to QAC; they are not susceptible to current QAC bacterial resistance machinery. Due to conformational flexibility, these compounds tend to escape such resistance mechanisms.[29]

2. Development

A very useful and most commonly used parameter for antimicrobial activity of the microbiocides comparison is minimum inhibitory concentration (MIC), i.e., the lowest concentration of compound inhibiting the visible growth of microorganisms after incubation. MIC values depend on several factors: concentration of active agent, time of the contact, pH, temperature, the presence of organic matter or other compounds, as well as nature, numbers, location, and condition of the microorganism. The main factor determining the antimicrobial activity of gemini surfactants is chemical structure. Antimicrobial efficiencies of homologues series of long chain surfactants show a non-linear dependence on chain length. This dependence is quasi parabolic, and named by  Devinsky as cut-off effect.[30][31] Such a relationship is characteristic of the homologous series of gemini surfactants: 3-oxa-1,5-pentane-bis(N-alkyl-N,N-dimethylammonium bromides) (n-O-n),[8] 3-methylaza-1,5-pentane-bis(N-alkyl-N,N-dimethylammonium) dibromides (n-N-n),[32] or 1,6-hexamethylene-bis(N-alkyl-N,N-dimethylammonium bromides) (n-6-n).[33] Compounds with short alkyl chain show the highest values of MIC, and minimal antimicrobial activity. The substituents are too short to effectively penetrate the outer shell of the microorganism’s cells. An increase in hydrocarbon substituent results in an increase in antimicrobial activity (lowering of MIC value). Compound with 12 carbon atoms in substituents proved to be the most active against microorganisms. Further increase in the hydrophobic chain results in a decrease in activity (increasing of MIC value), due to limited solubility in the aqueous. Compounds bearing functionalized spacers by ether (n-O-n) or amine (n-N-n) group show very similar antibacterial and antifungal activity.[8][32] Very close MIC values were also received for 12-6-12. Compounds 12-O-12, 12-N-12 and 12-6-12 have a similar molecular surface. Therefore, it can be concluded that the introduction of an electron-rich group into the spacer does not result in better adsorption of the microbiocide on the surface of the microorganism’s cell. Therefore, it does not involve an increase in antimicrobial activity. On the other hand, this GS possess better antibacterial activity than compared to analogic compounds with a stiff spacer constructed from an aromatic ring.[34] Compound 12-Ph-12 shows more than three times higher MIC values against S. aureus and E. coli than compared to 12-O-12. It is worth emphasizing that the GS show much greater antimicrobial activity than their monomeric counterparts. The MIC values of DTAB (N-dodecyl-N,N,N-trimethylammonium bromide) are 0.252, 0.36, and 0.5 mM against S. aureus, E. coli, and C. albicans, respectively.[10][35] 12-O-12 proved to be at least 30 times more active than DTAB. The most efficient microbiocide against all tested microorganisms is 12-O-12, which is comparable to the activity of compound 12-6-12. Compound 12-O-12 is a more than 30 times more efficient microbiocide than DTAB. Obtained GS are more active against Gram (+) bacteria than Gram (−) bacteria. These compounds constitute a new, interesting class of microbicides with a broad spectrum of biocidal activity.


  1. Bogumil E. Brycki; Iwona H. Kowalczyk; Adrianna Szulc; Olga Kaczerewska; Marta Pakiet; Multifunctional Gemini Surfactants: Structure, Synthesis, Properties and Applications. Application and Characterization of Surfactants 2017, 1 , 97-155, 10.5772/intechopen.68755.
  2. Yang Jiao; Li-Na Niu; Sai Ma; Jing Li; Franklin R. Tay; Ji-Hua Chen; Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance. Progress in Polymer Science 2017, 71, 53-90, 10.1016/j.progpolymsci.2017.03.001.
  3. Bogumił Brycki; Gemini alkylammonium salts as biodeterioration inhibitors.. Polish Journal of Microbiology 2010, 59, 227-231.
  4. F. M. Menger; C. A. Littau; Gemini-surfactants: synthesis and properties. Journal of the American Chemical Society 1991, 113, 1451-1452, 10.1021/ja00004a077.
  5. Fredric M. Menger; Jason S. Keiper; Gemini Surfactants. Angewandte Chemie International Edition 2000, 39, 1906-1920, 10.1002/1521-3773(20000602)39:11<1906::aid-anie1906>;2-q.
  6. F. M. Menger; C. A. Littau; Gemini surfactants: a new class of self-assembling molecules. Journal of the American Chemical Society 1993, 115, 10083-10090, 10.1021/ja00075a025.
  7. Bogumił Brycki; Adrianna Szulc; Gemini surfactants as corrosion inhibitors. A review. Journal of Molecular Liquids 2021, 344, 117686, 10.1016/j.molliq.2021.117686.
  8. Bogumil Eugene Brycki; Adrianna Szulc; Iwona Kowalczyk; Anna Koziróg; Ewelina Sobolewska; Antimicrobial Activity of Gemini Surfactants with Ether Group in the Spacer Part. Molecules 2021, 26, 5759, 10.3390/molecules26195759.
  9. Bogumił Brycki; Adrianna Szulc; Mariia Babkova; Synthesis of Silver Nanoparticles with Gemini Surfactants as Efficient Capping and Stabilizing Agents. Applied Sciences 2021, 11, 154, 10.3390/app11010154.
  10. Anna Koziróg; Bogumił Brycki; Monomeric and gemini surfactants as antimicrobial agents - influence on environmental and reference strains. Acta Biochimica Polonica 2015, 62, 879-883, 10.18388/abp.2015_1150.
  11. Chengcheng Zhou; Yilin Wang; Structure–activity relationship of cationic surfactants as antimicrobial agents. Current Opinion in Colloid & Interface Science 2019, 45, 28-43, 10.1016/j.cocis.2019.11.009.
  12. Bogumił Brycki; Małgorzata Drgas; Magdalena Bielawska; Anna Zdziennicka; Bronisław Jańczuk; Synthesis, spectroscopic studies, aggregation and surface behavior of hexamethylene-1,6-bis(N,N-dimethyl-N-dodecylammonium bromide). Journal of Molecular Liquids 2016, 221, 1086-1096, 10.1016/j.molliq.2016.06.075.
  13. Unnati Dani; Anita Bahadur; Ketan Kuperkar; Micellization, Antimicrobial Activity and Curcumin Solubilization in Gemini Surfactants: Influence of Spacer and Non-Polar Tail. Colloid and Interface Science Communications 2018, 25, 22-30, 10.1016/j.colcom.2018.06.002.
  14. Xiaofang Zhao; Yahong Li; Hao Yuan; Jianhua Yin; Mingming Hu; Antibacterial Mechanism of Octamethylene-1,8-Bis(Dodecyldimethylammonium Bromide) Against E. coli. Journal of Surfactants and Detergents 2017, 20, 717-723, 10.1007/s11743-017-1942-z.
  15. Bogumil Brycki; Iwona Kowalczyk; Anna Koziróg; Synthesis, Molecular Structure, Spectral Properties and Antifungal Activity of Polymethylene-α,ω-bis(N,N- dimethyl-N-dodecyloammonium Bromides). Molecules 2011, 16, 319-335, 10.3390/molecules16010319.
  16. Ewa Obłąk; Agata Piecuch; Anna Krasowska; Jacek Łuczyński; Antifungal activity of gemini quaternary ammonium salts. Microbiological Research 2013, 168, 630-638, 10.1016/j.micres.2013.06.001.
  17. Konrad Winnicki; Katarzyna Łudzik; Aneta Żabka; Justyna Teresa Polit; Anna Zawisza; Janusz Maszewski; Anti-algal activity of the 12-5-12 gemini surfactant results from its impact on the photosynthetic apparatus. Scientific Reports 2021, 11, 1-12, 10.1038/s41598-021-82165-9.
  18. Cassandra L. Schrank; Kevin P. C. Minbiole; William M. Wuest; Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe Acute Respiratory Syndrome-Coronavirus-2?. ACS Infectious Diseases 2020, 6, 1553-1557, 10.1021/acsinfecdis.0c00265.
  19. Thomas Thevenin; Pierre Emmanuel Lobert; Didier Hober; Inactivation of Coxsackievirus B4, Feline Calicivirus and Herpes Simplex Virus Type 1: Unexpected Virucidal Effect of a Disinfectant on a Non-Enveloped Virus Applied onto a Surface. Intervirology 2013, 56, 224-230, 10.1159/000350556.
  20. Stephanie L. Bolton; Grishma Kotwal; Mark A. Harrison; S. Edward Law; Judy A. Harrison; Jennifer L. Cannon; Sanitizer Efficacy against Murine Norovirus, a Surrogate for Human Norovirus, on Stainless Steel Surfaces when Using Three Application Methods. Applied and Environmental Microbiology 2012, 79, 1368-1377, 10.1128/AEM.02843-12.
  21. Megan C. Jennings; Bettina A. Buttaro; Kevin P. C. Minbiole; William M. Wuest; Bioorganic Investigation of Multicationic Antimicrobials to Combat QAC-Resistant Staphylococcus aureus. ACS Infectious Diseases 2015, 1, 304-309, 10.1021/acsinfecdis.5b00032.
  22. Elangeni A. Gilbert; Javier F. Guastavino; Rocío A. Nicollier; María Verónica Lancelle; Karen Russell-White; Marcelo C. Murguía; Synthesis and Properties of Cleavable Quaternary Ammonium Compounds. Journal of Oleo Science 2021, 70, 59-65, 10.5650/jos.ess20216.
  23. Bogumił Brycki; Adrianna Szulc; Gemini Alkyldeoxy-D-Glucitolammonium Salts as Modern Surfactants and Microbiocides: Synthesis, Antimicrobial and Surface Activity, Biodegradation. PLoS ONE 2014, 9, e84936, 10.1371/journal.pone.0084936.
  24. Olga Kaczerewska; Bogumił Brycki; Isabel Ribosa; Francesc Comelles; M. Teresa Garcia; Cationic gemini surfactants containing an O-substituted spacer and hydroxyethyl moiety in the polar heads: Self-assembly, biodegradability and aquatic toxicity. Journal of Industrial and Engineering Chemistry 2018, 59, 141-148, 10.1016/j.jiec.2017.10.018.
  25. O. Kaczerewska; Rafael Leiva Garcia; R. Akid; Bogumil Brycki; Iwona Kowalczyk; T. Pospieszny; Effectiveness of O -bridged cationic gemini surfactants as corrosion inhibitors for stainless steel in 3 M HCl: Experimental and theoretical studies. Journal of Molecular Liquids 2018, 249, 1113-1124, 10.1016/j.molliq.2017.11.142.
  26. O. Kaczerewska; R. Leiva-Garcia; R. Akid; B. Brycki; Efficiency of cationic gemini surfactants with 3-azamethylpentamethylene spacer as corrosion inhibitors for stainless steel in hydrochloric acid. Journal of Molecular Liquids 2017, 247, 6-13, 10.1016/j.molliq.2017.09.103.
  27. O. Kaczerewska; R. Martins; J. Figueiredo; Susana Loureiro; J. Tedim; Environmental behaviour and ecotoxicity of cationic surfactants towards marine organisms. Journal of Hazardous Materials 2020, 392, 122299, 10.1016/j.jhazmat.2020.122299.
  28. M. Teresa Garcia; Olga Kaczerewska; Isabel Ribosa; Bogumił Brycki; Paulina Materna; Małgorzata Drgas; Biodegradability and aquatic toxicity of quaternary ammonium-based gemini surfactants: Effect of the spacer on their ecological properties. Chemosphere 2016, 154, 155-160, 10.1016/j.chemosphere.2016.03.109.
  29. Kevin P.C. Minbiole; Megan C. Jennings; Laura E. Ator; Jacob W. Black; Melissa C. Grenier; Jade E. LaDow; Kevin Caran; Kyle Seifert; William Wuest; From antimicrobial activity to mechanism of resistance: the multifaceted role of simple quaternary ammonium compounds in bacterial eradication. Tetrahedron 2016, 72, 3559-3566, 10.1016/j.tet.2016.01.014.
  30. Pavol Balgavý; Ferdinand Devínsky; Cut-off effects in biological activities of surfactants. Advances in Colloid and Interface Science 1996, 66, 23-63, 10.1016/0001-8686(96)00295-3.
  31. Ferdinand Devínsky; Anna Kopecka-Leitmanová; František Šeršeň; Pavol Balgavý; Cut-off Effect in Antimicrobial Activity and in Membrane Perturbation Efficiency of the Homologous Series of N,N-Dimethylalkylamine Oxides. Journal of Pharmacy and Pharmacology 1990, 42, 790-794, 10.1111/j.2042-7158.1990.tb07022.x.
  32. Iwona Kowalczyk; Marta Pakiet; Adrianna Szulc; Anna Koziróg; Antimicrobial Activity of Gemini Surfactants with Azapolymethylene Spacer. Molecules 2020, 25, 4054, 10.3390/molecules25184054.
  33. F. Devinsky; I. Lacko; D. Mlynarčik; V. Račanský; L. Krasnec; Relationship Between Critical Micelle Concentrations and Minimum Inhibitory Concentrations for Some Non-Aromatic Quaternary Ammonium Salts and Amine Oxides. Tenside Surfactants Detergents 1985, 22, 10-15, 10.1515/tsd-1985-220105.
  34. Bogumił Brycki; Anna Koziróg; Iwona Kowalczyk; Tomasz Pospieszny; Paulina Materna; Jędrzej Marciniak; Synthesis, Structure, Surface and Antimicrobial Properties of New Oligomeric Quaternary Ammonium Salts with Aromatic Spacers. Molecules 2017, 22, 1810, 10.3390/molecules22111810.
  35. Shanshan Zhang; Shiping Ding; Jing Yu; Xuerui Chen; QunFang Lei; Wenjun Fang; Antibacterial Activity, in Vitro Cytotoxicity, and Cell Cycle Arrest of Gemini Quaternary Ammonium Surfactants. Langmuir 2015, 31, 12161-12169, 10.1021/acs.langmuir.5b01430.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 593
Entry Collection: Biopharmaceuticals Technology
Revisions: 2 times (View History)
Update Date: 28 Jan 2022