Arsenic: The King of Poisons

Was Napoleon murdered with arsenic? Probably not–historians now think that Napoleon died from stomach cancer. But arsenic was found in his hair. How did it get there? At the time arsenic was present in many products. A swatch of wallpaper from Napoleon’s home was shown to contain a popular, arsenic-based green pigment. Under the right conditions, arsenic fumes could have been produced. These fumes would not have contained enough arsenic to kill Napoleon, but they could have caused adverse health effects (2).

Many arsenic compounds are colorless, odorless, and tasteless, and before the mid-eighteen hundreds arsenic could not be easily detected in the body. For these reasons arsenic was the poison of choice in the Middle Ages. In fact, so many aristocrats were offed by arsenic that it became known as “the king of poisons, and the poison of kings” (1). But why is arsenic poisonous? To answer this question, we need to take a look at arsenic’s chemistry.

 

Arsenic chemistry

Arsenic is an element, meaning that it is composed of a single type of atom. The arrangement of electrons in the arsenic (As) atom and another atom, called phosphorus (P), is shown in the Bohr models below. Notice a similarity?

Bohr models show the arrangement of electrons in phosphorous and arsenic. These two elements are in the same group (or column) of the periodic table, which means that they have the same number of valence electrons and behave in a similar way.

In both phosphorous and arsenic the outermost electrons shell, called the valence shell, is partly filled with five valence electrons. A partly filled valence shell is less stable than a full shell, and atoms with a partly filled shell tend to transfer or share electrons to achieve a more stable electron configuration. When electrons are transferred or shared, a compound is formed.

Since arsenic and phosphorous have the same number of valence electrons, they tend to form similar compounds. For example, phosphorous forms a compound called phosphate, and arsenic forms an analogous compound called arsenate.

Phosphate is found in many biological molecules, including DNA and an important cellular fuel called ATP.

 

Phosphate forms the backbone of DNA.

Arsenate can be accidentally incorporated into biological molecules in place of phosphate. If arsenate was exactly the same as phosphate this wouldn’t matter. But it’s not. Look again at the Bohr models. The arsenic atom has a whole extra row of electrons, which means that it is slightly bigger. And this slightly bigger size makes a really big difference.

To see why, let’s consider a reaction called hydrolysis. Hydro means “water” and lysis means “unbind”, so hydrolysis literally means “to unbind with water”. In the hydrolysis reaction shown below, a water molecules removes (or unbinds) a phosphate from ATP.

ATP hydrolysis. An ATP molecule has an adenine (A) and three phosphates. In the reaction shown, the terminal phosphate is removed.

A lot of energy is released when the phosphate is removed. But often, the water molecule just can’t get close enough to react. This means that the ATP fuel is pretty stable: it sits there in the cell, until the cell is ready to use it.

Now, let’s consider what happens when arsenate replaces the terminal phosphate of ATP. Arsenic is a little bit bigger than phosphorus, and the As-O bond is a little bit longer than the P-O bond. This means that there is a bit more space between the oxygen atoms. A water molecule can get close more easily, and the hydrolysis reaction is faster. Not a little faster. A lot faster (3). As a result, the arsenic-containing fuel falls apart as soon as it is made.

Imagine what would happen if you filled your car’s tank and the gasoline was ruined before you finished pumping. You wouldn’t get anywhere, right? Likewise, a cell can’t do anything when its cellular fuel is ruined, which is what happens when the fuel is made from arsenate rather than phosphate. The cell keeps trying to make more fuel, and in so doing eventually exhaust its energy supply. Arsenate-containing DNA falls apart as well, and so do other molecules in which arsenate replaces phosphate. If enough arsenate is present, the cell dies.

Arsenate isn’t the only toxic form of arsenic. In fact, arsenite, which has one less oxygen than arsenate, is even more toxic for different reasons. Unfortunately arsenate turns to arsenite more easily than phosphate turns to the phosphite, all because the arsenic atom is a little bit different than the phosphorus atom (4).

Arsenic tolerance

Can living organisms ever use arsenate in place of phosphate? In 2010 scientists reported that GFAJ-1, a bacterium isolated from an arsenic-laced lake, could. However, subsequent studies showed that this bacterium always used phosphate, not arsenate, in DNA and other biological molecules even when the arsenic concentration was extraordinarily high (5).

To date, no life form is known that can substitute arsenate for phosphate. Nevertheless, certain organisms such as GFAJ-1 have adapted the ability to survive in high arsenic environments. A couple of different strategies for surviving in arsenic are described below.

Phosphate selectivity Phosphate is an important nutrient, and specialized transporters allow it to move into cells. Most phosphate transporters have a hard time distinguishing phosphate from arsenate, which means that any arsenate in the environment can be transported into cells along with phosphate. Some arsenic-tolerant bacteria, such as GFAJ-1, have phosphate transporters that are highly selective for phosphate (6). These transporters don’t move arsenate into cells even if it is present at very high levels, so it doesn’t cause any problems.

Arsenic detoxification and sequestration Other arsenic-tolerant bacteria are able to convert arsenate to less toxic compounds (7). Some plants are also arsenic tolerant. Interestingly, a group of plants called arsenic hyperaccumulators actively take up arsenate from the soil. In fact, the concentration of arsenic in the fronds of a hyperaccumulator called the Chinese brake fern (Pteris vittata) can be 56-times that in the soil (8). Arsenate-tolerant plants don’t use the arsenate; instead, they convert it to less toxic forms and sequester it in locations where it can do no harm (9).

The Chinese brake fern is an arsenic hyperaccumulator.

Arsenic tolerance of these plants confers a couple of advantages (9). First, arsenic-tolerant plants are the only ones that can survive in arsenic-contaminated soil, so they are not shaded by other plants. Second, experimental studies show that insects avoid hyperaccumulators grown in arsenic-contaminated soil, but feast on the same plants if they are grown in clean soil. These results indicate that the plants use arsenic as a natural insecticide.

Plants aren’t the only ones to use arsenic to fend off pests: humans do it, too. Historically, arsenic has been used as an insecticide, fungicide, herbicide, and wood preservative (1). Unfortunately, arsenic in pesticides and other products can contaminate the environment. For this reason the United States phased out the use of arsenic treated wood for residential applications in 2003. But many arsenic-treated structures still exist, and even after they are removed, the soil beneath them may contain arsenic.

Arsenic contamination is a big problem, but a company called Edenspace Systems has found a clever solution: this company uses arsenic-hyperaccumulating plants to draw arsenic out of contaminated soils. The fronds are then harvested and safely discarded.