New strategy for drug design: Keeping copper atoms closer to keep
bacteria away
Scientists engineer a copper-containing polymer that greatly boosts the antimicrobial activity of hydrogen peroxide

Date:
July 27, 2021
Source:
Tokyo University of Science
Summary:
Hydrogen peroxide reacts with copper to produce hydroxyl radicals
with strong antibacterial properties. However, this requires high
copper concentrations because two copper atoms have to come close
together, which occurs by chance. Now, scientists have engineered a
long polymer with copper-containing side units that create regions
with locally high copper density, boosting the antibacterial
activity of hydrogen peroxide and paving the way to a new drug
design concept.



FULL STORY ========================================================================== Hydrogen peroxide reacts with copper to produce hydroxyl radicals with
strong antibacterial properties. However, this requires high copper concentrations because two copper atoms have to come close together,
which occurs by chance.

Now, scientists at Tokyo University of Science, Japan, engineered
a long polymer with copper-containing side units that create regions
with locally high copper density, boosting the antibacterial activity
of hydrogen peroxide and paving the way to a new drug design concept.


==========================================================================
The discovery of antibiotics was a huge breakthrough in medicine,
which helped save countless lives. Unfortunately, their widespread use
has led to the rapid evolution of highly resistant bacterial strains,
which threaten to take humanity back to square one in the fight against infectious diseases. Even though researchers are seeking new design
concepts for antibacterial drugs, the overall development of new agents
is currently on the decline.

To tackle this serious problem, scientists at Tokyo University of Science, Japan, are exploring a novel approach to boost the in vivo antibacterial activity of hydrogen peroxide (H2O2), a commonly used disinfectant. In
a recent study published in Macromolecular Rapid Communications, a team
led by Assistant Professor Shigehito Osawa and Professor Hidenori Otsuka reported their success in enhancing H2O2 activity using carefully tailored copper-containing polymers.

To understand their approach, it helps to know how H2O2 acts against
bacteria in the first place, and the role that copper plays. H2O2 can be decomposed into a hydroxyl radical (oOH) and a hydroxide anion (OH-),
the former of which is highly toxic to bacteria as it readily destroys
certain biomolecules. Copper in its first oxidation state, Cu(I), can
catalyze the splitting of H2O2 into a hydroxyl radical and a hydroxide
anion, turning into Cu(II) in the process through oxidation. Curiously,
H2O2 can also catalyze the reduction of Cu(II) to Cu(I), but only if
this reaction is somehow facilitated. One way to achieve this is to have Cu(II)-containing complexes get close enough together.

However, when using Cu(II)-containing complexes dissolved in a solution,
the only way for them to come close together is by accidentally bumping
into each other, which requires an excessively high concentration of
copper. The team found a workaround to this issue by drawing inspiration
from cellular chemistry, as Dr. Osawa explains: "In living organisms,
copper forms complexes with proteins to efficiently catalyze redox
reactions. For example, tyrosinase has two copper complex sites in close proximity to each other, which facilitates the formation of reaction intermediates between oxygen species and copper complexes. We thought we
could leverage this type of mechanism in artificially produced polymers
with copper complexes, even if dispersed in a solution." With this idea,
the researchers developed a long polymer chain with dipicolylamine (DPA)
as copper-containing complexes. These DPA-copper complexes were attached
to the long polymer backbone as "pendant groups." When these polymers
are dispersed in a solution, the Cu(II) atoms in the pendant groups are
kept in close proximity and locally high densities, vastly increasing
the chances that two of them will be close enough to be reduced to Cu(I)
by H2O2.

Through various experiments, the scientists demonstrated that the use of
these tailored polymers resulted in higher catalytic activity for the
splitting of H2O2, resulting in more OHo even for lower concentrations
of copper. Further tests using Escherichia coli cultures showed that
these polymers greatly enhanced the antibacterial potential of H2O2.

While the results of this study open up a new design avenue for
antimicrobial drugs, there may also be useful applications in the food
industry as well.

"Because copper is an essential nutrient for living organisms,
the antibacterial agent developed in this study holds promise
as an efficient food preservative, which could contribute to
increasing the variety of foods that can be preserved over
long shelf times," highlights Dr. Osawa. Let us hope this new
strategy makes it easier for us to keep microscopic menaces at bay! ========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Shigehito Osawa, Kenichi Kitanishi, Maho Kiuchi, Motoyuki Shimonaka,
Hidenori Otsuka. Accelerated Redox Reaction of Hydrogen Peroxide
by Employing Locally Concentrated State of Copper Catalysts on
Polymer Chain. Macromolecular Rapid Communications, 2021; 2100274
DOI: 10.1002/ marc.202100274 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210727163230.htm

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