Luna, argentum, silver (Ag). As a metal of antiquity, the initial discovery of Ag is lost to history, but in the 21st century, its uses continue to evolve. My first introduction to Ag came as I was immersed in research on the creation of new antibiotics that target drug-resistant microbes. I was asked to evaluate Ag Oxysalts (Crawford Healthcare, Doylestown, PA), a unique silver compound (Ag7NO11). I approached this as I would a small molecule antibiotic, beginning with the question: How does chemistry influence antimicrobial efficacy?
Ag is mined from the earth as pure metallic Ag0(s) or the salt AgCl(s), neither of which has antimicrobial activity. This is because the soluble Ag ion (Ag1+) is required to capture electrons from bacterial cells, allowing Ag to be reduced back to a stable form (Ag0).1,2 Electrons are like currency within a bacterial cell. They enable the cell to generate the energy required for DNA replication, protein synthesis, and cell division. If electron transfer processes are disrupted, the cell cannot survive. Ag Oxysalts are different from other Ag compounds in many ways; this summary will focus on solubility and a higher reduction potential.
Where do soluble Ag ions come from? A salt is an ionic complex composed of equal numbers of positively and negatively charged ions. Ag can exist as different salt compounds such as silver chloride (AgCl), silver sulfate (Ag2SO4), or silver oxynitrate (Ag7NO11). The formulation of Ag salts can greatly influence stability, solubility, and subsequent antimicrobial activity.3,4 Some compounds such as AgCl are virtually insoluble (remember this stable compound represents a major source of mined silver). Other silver compounds, including Ag Oxysalts, are less stable and have high solubility in fluid, quickly releasing Ag ions to exert their activity. This is the case when oxygen is the anion used to stabilize positively charged Ag ions. Oxygen also is able to complex and stabilize more reactive Ag ions that exist in a higher oxidation state. This is a property that sets Ag Oxysalts apart from other Ag salts. Oxygen stabilizes the high reduction potential Ag2+ and Ag3+ ions, releasing oxygen alongside these highly reactive Ag ions when in contact with fluid.5-9
What does a higher reduction potential mean? Reduction potential measures the ability to acquire electrons. The higher the reduction potential, the stronger the affinity for capturing electrons. To put it simply, Ag2+ and Ag3+ are “stronger” than Ag+, allowing these ions to pull more electrons from different metabolic reactions and processes within a microbial cell (see Figure). For example, Ag3+ has a reduction potential of +1.80V compared to the +0.8V for Ag+ (see Table),10 and it needs to gain 3 electrons to get back to its stable state of Ag0 compared to only 1 electron for Ag+.
Speaking strictly about chemistry, solubility and reduction potential are 2 properties that influence antimicrobial activity. Compared side-by-side, Ag Oxysalts have the lowest minimum inhibitory concentration and minimum biofilm eradication concentration compared to other ionic Ag salts, resulting in less overall Ag use but greater efficacy.3,4
Clinically speaking, a highly soluble compound allows for bacteria to be killed faster. A higher reduction potential leads to higher efficacy. When you combine a highly soluble compound with high reduction potential, you have a compound that has the speed and strength to kill bacteria within a biofilm without cytotoxicity. Other properties to Ag Oxysalts, such as the release of oxygen, are currently being studied to understand the impact this compound has on wounds.