Analysis of Chemical Warfare Degradation Products

Chapter 1

Historical Milieu

1.1 Organophosphorus Nerve Agents

Organophosphorus (OP) type compounds, that is, derivatives containing the PO moiety, were first discovered in the 1800s when researchers were investigating useful applications for insecticides/rodenticides. There are many derivatives of organophosphorus compounds, however, the OP derivatives that are typically known as 'nerve agents' were discovered accidentally in Germany in 1936 by a research team led by Dr. Gerhard Schrader at IG Farben [1-4]. Schrader had noticed the effects and lethality of these organophosphorus compounds towards insects and began developing a new class of insecticides. While working towards the goal of an improved insecticide, Schrader experimented with numerous phosphorus-containing compounds, leading to the discovery of the first nerve agent, Tabun (or GA) (Figure 1.1).

Figure 1.1 Chemical structure of Tabun

The potency of these insecticides towards humans was not realized until there was yet another accident, which involved a Tabun spill. Schrader and coworkers began experiencing symptoms, such as miosis (constriction of the pupils of the eyes), dizziness and severe shortness of breath, with numerous effects lasting several weeks [1, 4, 5].

A number of years prior to Schrader's discovery, Adolf Hitler and the Nazi government required that all inventions with potential military significance must be reported to the government [1, 3, 4]. After Schrader's discovery, the government secretly became involved in the development of chemical weapons for military use and built several large classified facilities during World War II for the further investigation of these chemicals and the possibilities of their effectiveness as chemical weapons. Concentrated focus on this research area led to the discovery of other nerve agents, such as Sarin, which was discovered by Schrader and his team in 1938. It is believed that SARIN was creatively named using the initials of these workers: Schrader, Ambrose, Rudriger and van der Linde. Soman [4] and Cylcosarin were also discovered through the German research efforts during World War II.

The Allies did not learn of nerve agents until artillery shells filled with them were captured towards the end of the war. After the Allies seized control of various chemical plants and uncovered some of Germany's chemical weapons, they too began to develop research on nerve agent chemical weaponry [1]. The G-series naming system was created by the United States when it uncovered the German activities, labeling Tabun as GA (German Agent A), Sarin as GB, Soman as GD and Cyclosarin as GF. Studies suggest that further derivatives of the G-agents (derivatives of Sarin) were made either by Germany or by the Allies after they had begun research on chemical weapons [1, 5]. Because most of the lesser known agents were not mass produced, or compounded, and by the fact that most of the work was done in secrecy, there is relatively little literature on the lesser known Sarin derivatives. The German government incorporated several of these nerve agents into artillery shells, but never used them against any Allied targets. It was believed that German intelligence was aware that the Allies also possessed the knowledge of chemical warfare agents, or similar compounds, which deterred the Germans from using the agents for fear of extensive retaliation, which would perhaps have resulted in their own nerve agents being used against them [2, 5].

After the end of World War II, the Allied nations began to divide the captured chemical weapons amongst themselves, and continue research on chemical nerve agents [5]. Dr. Ranajit Ghosh was a scientist in the United Kingdom working as a chemist at Imperial Chemical Industries (ICI). Similarly to the organophosphate research performed by Schrader, Ghosh also found the compounds to be relatively effective pesticides. Ranajit Ghosh and J.F. Newman discovered a new organophosphorus compound at ICI in 1952, patenting the first V-agent, diethyl S-2-diethylaminoethyl phosphorothioate (VG). At the time, its potency was not fully understood and it was subsequently sold as a pesticide under the trade name Amiton. It was withdrawn a short while later, due to the fact that it was found to be too toxic for safe use.

As with Schrader's work with the first G-agent, the toxicity did not go unnoticed, and samples were sent to the British Armed Forces research facility in England for extensive evaluation. Only after further experiments was the agent Amiton renamed to VG. Through British research efforts, a new series of organophosphorus compounds were discovered, which were known as the V-series [5]. However, once the aggressive lethality of these compounds towards humans was realized, the British government halted all chemical weapons research within a few years. The V-series agents were considered to be some of the deadliest manmade substances, where only a single drop is enough to kill an adult. The research was not abandoned though, as the United States and the British governments decided to exchange information regarding the V-series technology for research on thermonuclear weapons [2-5]. The United States obtained knowledge of four agents, VG, VE, VM, and the most popular V-agent, VX, and began experimenting while producing large stockpiles of weaponized agents [5]. In addition to being known as V-agents, they are occasionally referred to as Tammelin's esters, after Lars-Erik Tammelin of the Swedish Institute of Defense Research, who was also conducting research on this class of compounds in 1952 [2, 4, 5]. He is not often cited for this research, mainly because his work was not widely publicized.

The United States was not the only other country interested in the investigation of organophosphorus nerve agents. Russia, too, had developed its own V-agent, known as Russian VX, or VR [5]. Not much is known about these agents in terms of research due to the secrecy of the former Soviet Union. Russian VX has similar properties to those of VX and is similar in toxicity as well. Other agents, known as Novichok agents, were also produced, although again not much is known about these agents either. It is presumed that the Novichok agents were initially more stable and less toxic versions to handle than the earlier nerve agents, simply because it was assumed that they worked as binary agents [5]. Once two binary agents are mixed, then the toxic and lethal agent is produced. As with the G-agents, much of the research involving V-series agents was carried out in secrecy. Other derivatives of the V-series agents are likely to exist, but probably demonstrate less toxic properties than VX or VR, or were simply not made in vast quantities. Thus, there is no accurate information of their existence.

1.2 Blister Agents

Blister agents are cytotoxic alkylating compounds and have the ability to produce chemical burns on the skin; they are chemicals that produce blisters. Blister agents are often also called vesicants, the etymology for which originates from Latin: vesica = bladder, blister [6].

Some examples of blister agents are: Lewisite, an organoarsenic compound; Sulfur Mustard, also known as Mustard Gas, a family of sulfur-based agents; Nitrogen Mustard, a family of agents with similar characteristics to the Sulfur Mustards, but nitrogen based; and Phosgene Oxime, a potent chemical warfare agent, dichloroformoxime, which falls under the CDC (Center for Disease Control and Prevention) category of blister agents, and is often referred to as nettle agent. Nettle agents (or urticants) produce corrosive skin conditions, such as urticaria, but not cutaneous blisters, therefore their classification as blister agents is often debatable [7, 8].

Lewisite was discovered over one hundred years ago, in 1903. In his doctoral thesis, Father Julius Arthur Nieuwland, Ph.D. (14 February 1878 to 11 June 1936), working at the Catholic University of America in Washington, DC, described his study of the reaction of acetylene gas with arsenic trichlorides in the presence of aluminum chloride [9] (Figure 1.2).

Figure 1.2 Reaction scheme of Lewisite

During the course of this work, he discovered Lewisite and was himself exposed to it and became ill for several days. Therefore, he decided to abandon the study in order to recover from the illness caused by the toxic substance created during his experiments, and also due to its potential use as a toxin.

During World War I, the main American Chemical Warfare Service (CWS) unit, the American University Experiment Station (AUES), was conducting research and experiments in order to develop new chemical warfare agents. The information from Nieuwland's thesis became of interest to Winford Lee Lewis, who was an associate professor of chemistry at Northwestern University before he volunteered for CWS research in Washington. He tried to repeat Nieuwland's experiments and, after some adjustments (such as the addition of hydrogen chloride before distillation), discovered that the mixture was composed of three similar arsenic-based compounds, which, depending on the number of acetylene molecules bonding with the arsenic trichloride, became known as: Lewisite 1, 2-chlorovinylarsonous dichloride; Lewisite 2, bis(2-chlorovinyl)arsinous chloride; and Lewisite 3, tris(2-chlorovinyl)arsine [5, 10, 11]. The CWS named the arsenic compounds after Lewis [1917], which turned out to be one of the most deadly poisonous gasses produced during World War I. It was also known as the 'Dew of Death', because it was often...