Synthesis and Applications By Hoang Le Chem12B-Spring 2006 PARAFORMALDEHYDES Synthesis and Applications By Hoang Le Chem12B-Spring 2006

ABSTRACT Paraformaldehydes, the polymer of formaldehydes, are the most commonly used fixatives. They serve to stabilize the fine structural details of cells and tissues prior to examination by light or microscopy. Beside fixatives function, paraformaldehydes can be used as decontaminant. Even though paraformaldehydes have many useful applications, they usually give unpleasant odors and are toxic substances. This presentation will briefly describe what are paraformaldehydes, their applications and their effects on human health.

OUTLINE Why did I choose paraformaldehydes? Paraformaldehydes, what they are and what they do? Toxicity of paraformaldehydes Comparison with others food preservation Conclusions

Why chose Paraformaldehydes? Curiosity in how animal’s tissues are preserved in biology lab. Anthrax crisis in 2002 and the need of decontamination. Its toxicity when it was used to preserve food.

Paraformaldehydes What they are? A polymer of formaldehydes A white crystalline powder with the odor of formaldehyde. Have chemical formular of (-HCHO-)n with n = 2 to 100

Paraformaldehydes the systhesis Paraformaldehydes can be synthesize by dissolve rapidly formaldehyde gas in water, with which they combine chemically to form methylene hydrate. HO-CH2-OH Methylene hydrate molecules react with one another, combining to form polymer.

Synthesis mechanism H2O + HH C=O HO-CH2-OH HO-CH2-OH n H-CH2-O-OH Methylene hydrate formaldehyde HO-CH2-OH n H-CH2-O-OH Formaldehyde polymer

Paraformaldehyes Applications Paraformaldehydes are widely used fixative. They have been used over century as a tissue preservative. Paraformaldehyes have been used as a decontaminant for more than 30 years.

Fixatives To be useful as a fixative, paraformaldehydes first have to be broken down to monomeric formaldehyde. Formaldehyde then reacts with active hydrogens atom of protein to form cross-link -CH2- called methylene bridge. This is Nucleophillic Addition reaction of amines to aldehyde.

Fixative mechanism. PROTEIN -H + HCHO -HCHOH + H- C H2 + H2O H2C O HH Step 1: depolymerization of paraformaldehydes H2C O 60oC (OH-) HH C=O 4 Formaldehyde (4 molecules) Paraformaldehyde (4 units within large polymer) Step 2: cross-link formation PROTEIN -H + HCHO -HCHOH + H- C H2 + H2O Methylene bridge

Decontaminant When heated releases formaldehyde gas, which can be used as decontaminant. Use to control harmful microorganisms such as bacteria, viruses, or fungi on inanimate objects and surface. Formaldehyde inactivate protein by forming covalent cross-links with several organic functional groups on protein.

Federal Anthrax decontamination During the course of October 2001, several government and commercial building were contaminated with spores of Bacillus anthracis, commonly known as anthrax. EPA had identified paraformaldehydes as potentially substance for anthrax decontamination.

Toxicity of paraformaldehydes When heated, paraformaldehydes produce fomaldehyde gas which identified as a mutagen and a carcinogen. Paraformaldehyde will inactivate and destroy proteins on cell membrane as well as in the tissue. As the result, the proteins will loose its functions. Cause damage to sight, cause skin or eye burns or irritation, cause severe burning of mouth and stomach, and cause heritable genetic damage.

Comparison with other food preservative The regular food preservatives are not toxic because they only target microorganism that cause food spoilage but they won’t affect human proteins. Food preservatives prevent protein synthesis in microorganism by targeting the function of 70s ribosome. Common food preservatives are Sulfur oxide, Sorbic acid, sodium benzoate, calcium propionate, and sodium nitrate.

Conclusion Paraformaldehydes were used as a tissue preservative for over a century. They were also used to decontaminate the surfaces which were contaminated by harmful microorganism. However, paraformaldehydes are toxic and harmful to human health and environment. Therefore, we need to have tight control and regulation for the manufacture and usage of paraformaldehydes.

References Helander, K.G.(1994). Kinetic studies of formaldehyde binding in tissue. Biotechnic & Histochemistry 69: 177-179. Hopwood, D. (1969). Fixatives and fixations: a review. Histochemical Journal 1: 323-360. http://publish.uwo.ca/~jkiernan/formglut.htm http://www.epa.gov/pesticides/factsheets/chemicals/paraformaldehyde_factsheet.html http://aic.stanford.edu/jaic/articles/jaic29-02-004_4.html http://ptcl.chem.ox.ac.uk/MSDS/PA/paraformaldehyde.html http://www.inchem.org/documents/ehc/ehc/ehc89.htm#SectionNumber:3.2