Готовый перевод мклаудт_тест / mclaudt_test: тестовая глава

In silico simulation of silver and copper ions interacting with fungal cell wall.

In vitro antifungal activity of copper ions and silver ions.

Annotation

The interaction of silver and copper ions with chitin dimers was modelled using quantum chemistry within the DFT framework.

A variation of parameters of hydrogen bonds depending on the presence of different metal atoms was obtained.

This variation was compared with the results of in vitro study of antifungal activity of corresponding metal ions.

Introduction

Silver has long been known to serve as antibacterial and antifungal agent.

Out of all the metals with similar antimicrobial properties, silver has the least toxicity to human cells.

Prior to the introduction of modern antibiotics, silver was commonly used in medical treatments.

-

The exact mechanism of antifungal activity is still unknown, and is currently the subject of many research.

There is three suggested qualitative concepts: DNA association, cell wall damage and deactivation of enzymes.

On the molecular level it is known that silver is capable to form a bond with S, N, and O atoms, and also to catalyze the formation of disulfide bonds.

-

The new computational quantum chemistry methods make it possible to directly simulate biochemical processes which involve large molecules.

In this work the interaction of silver and copper ions with chitin dimers was modelled using the DFT theory.

Methods

Fungal cell wall simulated as two chitin dimers.

To obtain the optimized geometry of ground state, several DFT codes were used, including PC GAMESS, SIESTA and ABINIT.

Pic. 1. Conceptual map of DFT method.

To find the most probable area of metal adsorption on a molecule, Fukui functions scheme was used.

Pic. 2. Visualisation of a scalar electrophilic Fukui function, mapped onto the isosurface of electron density field for detection of probable adsorption site.

Electron density of ground state chitin system with adsorbed metal atoms was projected on atomic sites, responsible for hydrogen bond formation, using Hirshfeld method.

Calculations were performed on Linux-cluster using parallel MPI (MPICH2) и SMP (OpenMP) parallel paradigms.

In silico calculations were complemented by in vitro assay, in which we compared antifungal activity of silver and copper ions in the same concentrations against Alternaria alternata.

Results

Chitin dimers form the hydrogen bonds with each other, and there is a variability of parameters of that bond depending on type of adsorbed atom near bond.

Adsorbed silver atom increases the symmetry of H-bond, measured by the difference of projected charges on oxygen atoms, involved in H-bond, whereas copper atom decreases that symmetry, comparing to the original system without any metal.

Pic. 3. Ground state geometry of chitin dimers with silver atoms adsorded. Hydrogen bonds are shown by dash lines.

Projected atomic charge is shown near atom.

Pic. 4. Difference between the effects of adsorbed copper and silver on hydrogen bonds between chitin dimers.

Arrow depicts the polarity of Me-O bond.

Tab. 1. Calculated values of hydrogen bond parameters for original system and system witth metal atoms.

System

Total charge

Length

H-bond

Charge of farthest oxygen atom

Charge of nearest oxygen atom

Charge of metal atom

Charge on hydrogen atom

Chitin

Chitin + Ag

Chitin + Cu

In vitro study shows increased antifungal activity of silver comparing with copper in the same concentration.

Fig. 1. Growth dynamic of Alternaria alternata under two different silver and copper ions concentrations. С1 = 25 microg/ml (by metal mass) и С2 = 2.5 microg/ml (by metal mass).

Conclusion

The interaction with cell wall and the effect on the mechanical properties of its chitin skeleton could take part in antifungal mechanism of silver ions.

It correlates with observed low toxicity of silver for animal cells.

Decrease of the symmetry of hydrogen bonds, induced by copper atom adsorbtion, correlates with low antifungal activity of copper, comparing to silver atoms, which demonstrate increase of symmetry and high antifungal activity.

It could be an important parameter for mechanical properties of chitin skeleton, and changing of that parameter could take part in molecular mechanism of antifungal activities of silver ions.

Bibliography

Переведено на Нотабеноиде
http://notabenoid.org/book/36676/131660

Переводчики: mclaudt