|
Медико-биологический
информационный портал
|
 |
для специалистов |
|
|
|
Vol. 25, Art. 32 (pp. 582-596) | 2024
The structure and mechanism of antimicrobial action of the complex compound chlorhexidine, a new representative of nanodesinfectants
Galinkin V.A. 1 Enikeev A.H..1, Krasnov K.A.2 , Gladchuk A.S.2 , Gerasimov V.N.3,
Khrustalev V.N.4 1 − ROSBIO LLC, 192019, Russia, St. Petersburg, 10-A Melnichnaya str. 7731254@mail.ru 2 − Federal State Budgetary Institution «Scientific and Clinical Center of Toxicology named after academician S.N. Golikov of the Federal Medical and Biological Agency, 192019, Sankt-Peterburg, str. Behtereva, 1, institute@toxicology.ru , krasnov_tox@mail.ru 3 − Federal State Budgetary Institution "State Scientific Center of Applied Microbiology and Biotechnology" of Rospotrebnadzor 142279, Moscow region, Serpukhov district, village Obolensk, FBUN SSC PMB, ilcvngerasimov@obolensk.org 4 − Federal State Autonomous Educational Institution of Higher Education "Patrice Lumumba Peoples' Friendship University of Russia" Miklukho-Maklay str., 6
Brief summary
The formation of resistance of pathogenic microorganisms to known disinfectants (DA) requires constant improvement of the arsenal of DA. The effectiveness of DA can be increased by modification by combining known antiseptics with complexing agents. An example of this approach is the DA "Trihexilon" studied in this work − a complex antiseptic based on chlorhexidine (HCG), which has a higher biocidal activity and a wider spectrum of action compared with HCG. The active substance is a three-component complex of HCG with zinc chloride and ethylenediaminetetraacetic acid (EDTA), the methods of X-ray diffraction (XRD) and mass spectrometry have established the bichelate structure of this complex, formed by a two-charge chlorhexidinium cation, a two-charge zinc cation and a four-charge EDTA anion, In solutions, the complex aggregates to form nanoparticles of 50-150 nm in size. The data obtained indicate that the antiseptic effect of the HCG-Zn-EDTA complex is associated with a damaging effect on cell membranes. The aim of the study. To study the molecular structure and mechanism of antimicrobial action of a new three-component complex based on chlorhexidine, zinc and ethylenediaminetetraacetic acid. Materials and methods. The substance under study is a complex of Chlorhexidine-zinc-EDTA (disinfectant "Trihexilon" that contain of 0.2% in terms of chlorhexidine in the solution). The structure of the complex was studied in the crystalline state by X-ray diffraction analysis on a Rigaku SynergyS diffractometer, in solutions by matrix-activated laser desorption/ionization mass spectrometry (MALDI−MS) using an UltrafleXtreme mass spectrometer (Bruker Daltonics), elemental analysis and transmission electron microscopy. Microbiological studies were carried out using a test culture of Pseudomonas aeruginosa bacteria ATCC 27853B, the bactericidal activity of the drug was studied by electron microscopic methods using a TecnaiG2 SpiritBioTWIN tracer electron microscope. The degree of damage to the ultrastructure of microorganisms was assessed on the basis of cytostructural criteria, the viability of bacterial cells was assessed by microbiological method. Outcomes. For the first time, an X-ray diffraction study of the Chlorhexidine-Zn-EDTA complex was carried out and its fine molecular structure in the crystalline state was established. The complex is a stable bis-chelate electroneutral system in which the chlorhexidine molecule adopts a compact conformation stabilized by interaction with an anionic zinc-EDTA fragment. In solutions, the complex aggregates to form nanoparticles of 50-150 nm in size. The data obtained indicate that the antiseptic effect of the Chlorhexidine-Zn-EDTA complex is associated with a damaging effect on cell membranes. Conclusion. The structure and properties of the biocidal three-component complex Chlorhexidine-Zn-EDTA, which is a stable bichelate system, significantly distinguish it from free chlorhexidine. In solutions, the complex is represented by nanoparticles of 50-150 nm in size, which makes it possible to classify it as nanodesinfectants. The antiseptic effect of the Chlorhexidine-Zn-EDTA complex is realized through cell membranes, its increased activity is probably due to its small molecular volume, high mobility and tendency to form supramolecular structures. All this serves as a basis for further study of the mechanisms of the biocidal action of the Chlorhexidine-Zn-EDTA complex, which seems to be a promising basis for obtaining highly effective disinfectants. Key words chlorhexidine, complex, zinc, EDTA, disinfectant, nanoparticles, electron microscopy, X-ray diffraction analysis, MALDI mass spectra, bacterial ultrastructure. (The article in PDF format. For preview need Adobe Acrobat Reader)  Open article in new window
Reference list 1. Rasporyajenie Pravitelstva RF ot 25.09.2017 № 2045-r «Strategiya predyprejdeniya rasprostraneniya antimikrobnoi rezistentnosti v Rossiiskoi Federacii na period do 2030 goda» 2. Fedorova L.S., Ilyakova A.V. Aktyalnie voprosi rezistentnosti mikroorganizmov k dezinficiryushim sredstvam. Dezinfekcionnoe delo. 2022; 4(122): 50-54. 3 Udin M.A., Stepanov A.V., Bogacheva A.S. i dr. Perspektivnie podhodi k preodoleniu antibiotikorezistentnosti. Medline.ru. 2024; 25(1): 49-70. 4. Galinkin V.A., Enikeev A.H., Podolskaya A.S. i dr. Antimikrobnaya i virylicidnaya aktivnost trehkomponentnogo kompleksa hlorgeksidin-EDTA-cink. Medicina ekstremalnih sityacii. 2022; 1(24): 43-50. 5. Kvashnina D.V., Kovalishena O.V. Ocenka primeneniya hlorgeksidina kak antisepticheskogo sredstva. Medicinskii almanah. 2016; 43(3): S. 62-66 6. Zverkov A.V., Zyzova A.P. Hlorgeksidin: proshloe, nastoyashee i bydyshee odnogo iz osnovnih antiseptikov. Antimikrobnie preparati. 2013; 15(4): 279-285. 7. Gilbert P., Moore L.E. Cationic antiseptics: diversity of action under a common epithet. J. Appl Microbiol. 2005; 99: 703-715. 8. Mashkovskii M.D. Lekarstvennie sredstva. 16-e izd. M.: Novaya volna; 2012. 9. Junco-Lafuente, M.P., Baca-García, P., Mesa-Aguado, F.L. Utilización de la clorhexidina en la prevención oral de pacientes de la tercera edad. Revista del Ilustre Consejo General de Colegios de Odontólogos y Estomatólogos de España. 2001; 6: 81-89. 10. Jones C. G. Chlorhexidine: Is It Still the Gold Standard? Periodontol 1997; 15: 55-62. 11 Carrouel F., Conte M.P., Fisher J. at all. COVID-19: A Recommendation to Examine the Effect of Mouthrinses With β-Cyclodextrin Combined With Citrox in Preventing Infection and Progression. J. Clin Med. 2020; 9: 1126. 12. Wand M.E., Bock L.J., Bonney L.C., Sutton J.M. Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine. Antimicrob. Agents Chemother. 2017; 61: e01162-16. 13. CrysAlisPro, Version 1.171.41.106a. Oxford Diffraction, 2021. 14. Sheldrick G.M. Crystal Structure Refinement with SHELXL. Acta Crystallogr. 2015; 71: 3-8. 15. Rykovodstvo R 4.2.3676-20 «Metodi laboratornih issledovanii i ispitanii dezinfekcionnih sredstv dlya ocenki ih effektivnosti i bezopasnosti», M., 2020. 16. Gerasimov V.N., Marinina N.N., Harseeva G.G., Sherbataya O.S. Vozmojnosti transmissionnoi elektronnoi mikroskopii v ocenke kachestva kletok bakterii i mikrobnoi popylyacii. Klinicheskaya laboratornaya diagnostika. 2022; 67(4): 237-244. |
|||||||||
Articles
| Размещение рекламы | |
| |
 |