How does Lewis acidity correlate with bactericidal activity? I read on Wikipedia that the two are positively correlated but no explanation was given.

Does it have to do with the movement of electrons - i.e. a current? I'm guessing that having a current passed through you isn't good for you.

I suppose also that the interactions (i.e. coordination bonds) of metal (ions) with bacterial components can interfere with cellular processes.

  • $\begingroup$ Do you have a link to the article? $\endgroup$
    – canadianer
    Jun 2, 2014 at 18:41
  • 1
    $\begingroup$ Yes. " Antimicrobial efficacies generally followed Lewis acidity values of the various metals." en.wikipedia.org/wiki/Antimicrobial_copper-alloy_touch_surfaces $\endgroup$
    – Dissenter
    Jun 2, 2014 at 19:01
  • $\begingroup$ Perhaps this would get more attention on biology SE. You might try reading this (if you haven't already): en.wikipedia.org/wiki/… I would imagine that a stronger Lewis acid would be more likely to participate in those mechanisms because it is more able to accept electrons. $\endgroup$
    – canadianer
    Jul 13, 2014 at 2:42

2 Answers 2


Metal ions are by far some of the most common biological Lewis acids, and are vital to the function of many different cell activities. Excess of a particular species of metal ion, however, can result in cytotoxicity both by catalyzing certain reactions, and inhibiting others by coordinating with unbonded electron pairs present on atoms in many macromolecules, particularly sulfur. In the examples I am presenting, copper, zinc, and silver ions all exhibit their cytotoxicity by forming coordination complexes with the molecules within the cell, hindering their function.

Note: I have emboldened the exact reasons for the cytotoxicity within the text for ease of reading.


Recent evidence suggests a copper toxicity mechanism in which the reduced $\ce{Cu+}$ ion is instrumental. Multiple investigators note that copper toxicity to bacteria is sustained or even enhanced in anoxic conditions where peroxide formation is minimal. $\ce{Cu+}$ toxicity in the E. coli cytosol can be explained by its intense thiophilicity, which is sufficient to competitively disrupt key cytoplasmic iron-sulfur enzymes both in vitro and in vivo. Indeed, other “soft” thiophilic metal ions have been found to exert comparable toxicity. Together, these data provide compelling evidence linking copper toxicity to iron displacement from solvent-exposed dehydratase iron-sulfur clusters, resulting in metabolic disruption and branched chain amino acid auxotrophy.


Although nearly 30% of all proteins contain metal ions, an excess of certain transition metal ions can exert significant toxicity. The potential roles of such metals in resisting bacterial invasion are increasingly being recognized. Notably the importance of copper in macrophages for bactericidal activity has recently been demonstrated. Our present study provides the first direct evidence that extracellular $\ce{Zn(II)}$ can exert its toxicity towards S. pneumoniae by competing with $\ce{Mn(II)}$ for binding to the PsaA (Pneumococcal surface adhesin A) solute binding protein, thereby preventing the acquisition of $\ce{Mn(II)}$ via the Psa permease.


It is thought that silver atoms bind to thiol groups ($\ce{-SH}$) in enzymes and subsequently cause the deactivation of enzymes. Silver forms stable $\ce{S-Ag}$ bonds with thiol-containing compounds in the cell membrane that are involved in transmembrane energy generation and ion transport. It is also believed that silver can take part in catalytic oxidation reactions that result in the formation of disulfide bonds ($\ce{R-S-S-R}$). Silver does this by catalyzing the reaction between oxygen molecules in the cell and hydrogen atoms of thiol groups: water is released as a product and two thiol groups become covalently bonded to one another through a disulfide bond. The silver-catalyzed formation of disulfide bonds could possibly change the shape of cellular enzymes and subsequently affect their function.

The silver-catalyzed formation of disulfide bonds can lead to changes in protein structure and the inactivation of key enzymes, such as those needed for cellular respiration. 30S ribosomal subunit protein, succinyl coenzyme A synthetase, maltose transporter (MalK), and fructose bisphosphate adolase were identified with high probability as proteins with decreased expression once cells are treated with a $\mathrm{900\:ppb\:\ce{Ag+}}$ solution. It is hypothesized that silver ions bind to the 30S ribosomal subunit, deactivating the ribosome complex and preventing translation of proteins. The proteins that were found to be downregulated upon treatment with $\ce{Ag+}$ serve important functions to the cell: succinyl-coenzyme A synthetase, an enzyme involved in the TCA cycle, catalyzes the conversion of succinyl-CoA to succinate while phosphorylating ADP to produce ATP; fructose bisphosphate adolase is an enzyme involved in glycolysis that catalyzes the breakdown of fructose-1,6-bisphosphate into glyceraldehydes 3-phosphate and dihydroxyacetone phosphate; MalK is a cytoplasmic membrane-associated protein involved in the transport of maltose. In one way or another, all of these proteins play a role in energy and ATP production for the cell, so the decreased expression of any one of these proteins could lead to cell death.

Another one of the suggested mechanisms of the antimicrobial activity of silver was that $\ce{Ag+}$ enters the cell and intercalates between the purine and pyrimidine base pairs disrupting the hydrogen bonding between the two anti-parallel strands and denaturing the DNA molecule. Although this has yet to be proved, it has been shown that silver ions do associate with DNA once they enter the cell.

[1] Chaturvedi, K. S.; Henderson, J. P. Pathogenic Adaptations to Host-Derived Antibacterial Copper. Front. Cell. Infect. Microbiol. Frontiers in Cellular and Infection Microbiology. 2014, 4.

[2] Mcdevitt, C. A.; Ogunniyi, A. D.; Valkov, E.; Lawrence, M. C.; Kobe, B.; Mcewan, A. G.; Paton, J. C. A Molecular Mechanism For Bacterial Susceptibility to Zinc. PLoS Pathog PLoS Pathogens. 2011, 7.

[3] https://microbewiki.kenyon.edu/index.php/Silver_as_an_Antimicrobial_Agent#Mechanism_of_action


A review on $\ce{Ag+}$ quotes the following situations, which may be provoked by the Lewis acidic behavior of a metal cation.

  • Silver treated cells exhibited electron-light regions in their cytoplasm thus forcing DNA to condense. Authors state that condensed DNA molecules lose their ability to replicate.

I presume that $\ce{Ag+}$, acting as a Lewis acid, will reduce the negative charge on DNA, thus inducing DNA aggregation.

  • Electron-dense region were also observed around the cell wall inside the cytoplasm, and the cytoplasmic membrane experienced shrinkage and detachment from the cell wall.

  • There was also indication that silver ions interact with thiol groups leading to the deactivation of enzymatic proteins.

Here one sees the action of $\ce{Ag+}$ on thiols which may be interpreted as an acid-base interaction of the Lewis type.

  • Also the effect of $\ce{Ag+}$ on the respiratory electron chain of E. coli was stressed, since $\ce{Ag+}$ is toxic to microorganisms due to inhibition of the respiratory chain at multiple sites.

It appears that in many cases, one can link the antibacterial function of metal ions to their acidic properties. And certainly, those discussed above are not the only ones.


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