Cytosine
CHEMICAL NAME = 4-Aminopyrimidin-2(1H)-one CAS NUMBER = 71–30–7
MOLECULAR FORMULA = C4H5N3O MOLAR MASS = 111.1 g/mol
COMPOSITION = C(43.2%) H(4.5%) N(37.8%) O(14.4%) MELTING POINT = 100°C
BOILING POINT = Decomposes at 320°C DENSITY = 1.55 g/cm3 (calculated)
Thymine
CHEMICAL NAME = 5-Methylpyrimidine-2,4(1H,3H)-dione CAS NUMBER = 65–71–4
MOLECULAR FORMULA = C6H6N2O2 MOLAR MASS = 126.1 g/mol
COMPOSITION = C(47.6%) H(4.8%) N(22.2%) O(25.4%) MELTING POINT = 316°C
BOILING POINT = Decomposes at 335°C DENSITY = 1.23 g/cm3 (calculated)
Uracil
CHEMICAL NAME = Pyrimidine-2,4(1H,3H)-dione CAS NUMBER = 66–22–8
MOLECULAR FORMULA = C4H4N2O2 FORMULA WEIGHT = 112.1 g/mol
COMPOSITION = C(42.9%) H(3.6%) N(25.0%) O(28.6%) MELTING POINT = 335°C
Pyrimidine
Cytosine, thymine, and uracil are pyrimidines; along with adenine and guanine they account for the fi ve nucleic acid bases. Pyrimidines are heterocyclic single-ringed compounds based on the structure of pyrimidine. Cytosine, thymine, and uracil, like adenine and guanine, form nucleosides and nucleotides in RNA and DNA. When the bases combine with ribose, a ribo-nucleoside forms; and when it attaches to deoxyribose, a deoxyriboseribo-nucleoside is formed.
Names of the nucleoside are summarized in Table 29.1. Th ese in turn combine with phospho-ryl groups, in a process called phosphophospho-rylation, to form their respective nucleotides that form nucleic acids. Th e nucleotides can be tri, di, and mono phosphate nucleotides similar to the way in which adenine forms ATP, ADP, and AMP.
In nucleic acid base pairing, adenine (A) groups bond to thymine (T) groups and guanine (G) groups bond to cytosine (C) in DNA. In RNA, uracil (U) replaces thymine so that the base pairing is adenine to uracil in RNA. Cytosine, thymine, and uracil have similar structures and human genetics involves reactions where one base can be converted to another. Th e deam-ination (removal of NH2 group) of cytosine produces uracil. Th is helps explains why uracil is not normally present in DNA. If U were present rather than thymine, a G-U pairing could come from the cytosine in the C-G pairing converting to uracil. Th is would produce a U-G mismatch. Th is mismatch could also occur if the adenosine in an A-U pairing, which would normally occur if uracil replaced thymine, mutated to guanine. In short, U would not form
Table 29.1 Nucleosides
Ribonucleoside Deoxyribonucleoside Cytosine Cytidine Deoxycytidine
Thymine Thymidine Deoxythymidine Uracil Uridine Deoxyuridine BOILING POINT = Decomposes
DENSITY = 1.32 g/cm3
Cytosine, Th ymine, and Uracil | 93
94 | Th e 100 Most Important Chemical Compounds
a distinct base pair, making it possible to distinguish normal and mutagenic conditions. Th e presence of thymine means that any uracil found in DNA is a general indication of mutation.
Biochemical processes occur to remove the uracil in DNA and replace it with cytosine. Th us the methylation of uracil to thymine in DNA synthesis protects the DNA molecule.
Cytosine and thymine were fi rst isolated by hydrolysis of calf thymus tissue by Albrecht Kossel (1853–1927) and A. Neumann during 1893–1894. Th ymine’s structure was pub-lished in 1900 and confi rmed over the next several years when it was synthesized by several investigators. In 1903, cytosine was synthesized by Henry Lord Wheeler (1867–1914) and Treat B. Johnson, confi rming its structure. Uracil was fi rst isolated in 1900 from yeast nucleic acid found in bovine thymus and herring sperm. Th e methylation of uracil produces thymine; thymine is also called 5-methyluracil because methylation takes place at the fi fth carbon in uracil to produce thymine.
Th e amine bases in DNA are adenine, thymine, cytosine, and guanine, symbolized by A,T, C, and G, respectively. RNA contains adenine, cytosine, and guanine, but thymine is replaced by the base uracil. Th e primary structure of nucleic acids is given by the sequence of the amine side chains starting from the phosphate end of the nucleotide. For example, a DNA sequence may be T-A-A-G-C-T. Genes, residing in the chromosomes, are segments of the DNA molecule. Th e sequence of nucleotides, represented by their letters, corresponding to a specifi c gene may be hundreds or even thousands of letters long. Humans have between 50,000 and 100,000 genes contained in their 46 chromosomes, and the genetic code in humans consists of roughly 5 billion base pairs.
Th e process by which the information in DNA is used to synthesize proteins is called transcription. Transcription involves turning the genetic information contained in DNA into RNA. Th e process starts just like DNA replication with the unraveling of a section of the two strands of DNA (see Adenine). A special protein identifi es a promoter region on a single strand.
Th e promoter region identifi es where the transcription region begins. An enzyme called RNA polymerase is critical in the transcription process. Th is molecule initiates the unwinding of the DNA strands, produces a complementary strand of RNA, and then terminates the process. After a copy of the DNA has been made, the two DNA strands rewind into their standard double helix shape. Th e RNA strand produced by RNA polymerase follows the same process as in DNA replication except that uracil replaces thymine when an adenosine is encountered on the DNA strand. Th erefore, if a DNA sequence consisted of the nucleotides: C-G-T-A-A, the RNA sequence produced would be G-C-A-U-U. Th e transcription process occurs in the cell’s nucleus and the RNA produced is called messenger RNA or mRNA. Once formed, mRNA moves out of the nucleus into the cytoplasm where the mRNA synthesizes proteins. Th e transfer of genetic information to produce proteins from mRNA is called translation. In the cytoplasm, the mRNA mixes with ribosomes and encounters another type of RNA called transfer RNA or tRNA.
Ribosomes contain tRNA and amino acids. Th e tRNA translates the mRNA into three-letter sequences of nucleotides called codons. Each three-letter sequence corresponds to a particular amino acid. Because there are four nucleotides (C, G, A, and U), the number of diff erent codons would be equal to 43 or 64. Because there are only 20 standard amino acids, several codons may produce the same amino acid. For example, the codons GGU, GGC, GGA, and GGG all code for glycine. Th ree of the codons serve as stop signs to signal the end of the gene. Th ese stops also serve in some case to initiate the start of a gene sequence. Th e sequential translation of mRNA by tRNA builds the amino acids into the approximately 100,000 proteins in the human body.
30. DDT
CHEMICAL NAME = 1-chloro-2-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene
CAS NUMBER = 50–29–3
MOLECULAR FORMULA = C14H9Cl5 MOLAR MASS = 354.5 g/mol
COMPOSITION = C(47.4%) H(2.6%) Cl(50.0%) MELTING POINT = 108.5°C
BOILING POINT = 260°C DENSITY = 1.5 g/cm3
DDT is a polychlorinated persistent chemical that exists as a solid under normal conditions.
In 1939, the Swiss chemist Paul Müller (1899–1965), working for the Geigy chemical com-pany, discovered that the compound dichlorodiphenyltrichloroethane (DDT) was an eff ective insecticide. DDT was fi rst synthesized in 1873 by an Austrian student, but it was Müller who discovered its effi cacy as an insecticide. DDT was initially marketed in 1941 and found its fi rst widespread use during World War II. During World War I several million deaths, includ-ing 150,000 soldiers, were attributed to typhus. Th ere are several forms of typhus, but the most common form is due to bacteria carried by lice. During World War II, fearing a repeat of World War I typhus outbreaks, the Allied forces used DDT to combat typhus in addition to malaria, yellow fever, and other diseases carried by insects. Soldiers liberally applied talcum powder containing 10% DDT to clothes and bedding to kill lice. America and its European allies were relatively free from typhus and other diseases, whereas the Germans, who did not use DDT, had many more noncombat deaths resulting from infectious diseases. DDT solutions were sprayed in areas of the Pacifi c Th eater to prevent malaria and yellow fever. In addition to its use in the war, DDT was used by civilians in tropical areas as a generic insecti-cide to prevent infectious diseases, especially malaria. Once the war ended, the use of DDT to advance public health in tropical developing countries was expanded for use in agriculture in developed countries. Paul Müller was awarded the Nobel Prize in physiology or medicine in 1948 for his discovery of the insecticide potential of DDT. By 1950, DDT and several related
96 | Th e 100 Most Important Chemical Compounds
compounds were viewed as miracle insecticides that were inexpensive and that could be used indiscriminately.
Even though DDT seemed to be a cheap and eff ective pesticide, enough was known in its early development to raise concerns. DDT is a persistent chemical that lasts a long time in the environment. DDT is fat-soluble and not readily metabolized by higher organisms. Th is meant that DDT accumulated in the fat tissues of higher organisms. Organisms with longer life spans residing higher on the food chain continually fed on organisms lower on the food chain, accumulating DDT in their tissues. For example, the concentration of DDT in a lake might be measured in parts per trillion, plankton in the lake may contain DDT in parts per billion, fi sh a few parts per million, and bird feeding on fi sh from the lake several hundred parts per million. Th e accumulation of a chemical moving up the food chain is a process known as biological magnifi cation (Figure 30.1). Another concern was that certain pests seemed to develop immunity to DDT and the application rate had to be increased to combat insects. Th is immunity occurred because natural selection favored insects that had the genetic characteristics to survive DDT and passed this ability on to their off spring. Direct deaths of bird and fi sh populations had also been observed in areas with heavy DDT use. Problems associated with DDT and other post World War II organic pesticides became a national concern with Rachael Carson’s (1906–1964) publication of Silent Spring in 1962. Carson’s book alerted the public to the hazards of insecticides, and although the book did not call for a ban, Carson challenged the chemical and agricultural industry to curtail its widespread use of chemical pesticides. Most developed countries started to ban the use of DDT and related compounds in the late 1960s. DDT was banned in the United States in 1973. Although it has been banned in developed countries, its use to improve public health in developing coun-tries continues. Th e World Health Organization estimates that DDT has saved 25 million lives from malaria and hundreds of millions of other lives from other diseases.
Figure 30.1 Pollutants can be concentrated as they move up the food chain.
Drawing by Rae Déjur.
DDT | 97
Th e United Nations’ Stockholm Treaty on persistent organic pollutants calls for the phase out of DDT but recognizes its effi cacy as a deterrent to vector-borne diseases such as malaria and typhus. According to the treaty, the continued use of DDT is discouraged, but until eff ec-tive economical alternaec-tives are found, DDT use will be continued in countries with high rates of vector diseases. A number of developing countries still use DDT. It is applied primarily in the interior of homes to prevent malaria. Currently DDT is produced only in India and China, and current production volumes are unknown.
DDT belongs to a group of chemical insecticides know as organochlorides. Th ese contain hydrogen, carbon, and chlorine and kill by interfering with nerve transmission, making them neurotoxins. Organochlorides were the dominant type of chemical insecticide used from 1940 to 1970. Some common organochlorides besides DDT are chlordane, heptachlor, aldrin, and dieldrin. Because of their problems and subsequent ban in many regions, numerous other classes of insecticides have been synthesized to replace organochlorides.
31. DEET
CHEMICAL NAME = N,N-diethyl-3-methylbenzamide CAS NUMBER = 134–62–3
MOLECULAR FORMULA = C12H17NO MOLAR MASS = 191.3 g/mol
COMPOSITION = C(75.4%) H(9.0%) N(7.3%) O(8.4%) MELTING POINT = −45°C
BOILING POINT = 285°C DENSITY = 1.0 g/cm3
DEET has been used for more than 50 years as the active ingredient in many insect repel-lent formulations. It is used to repel biting pests such as mosquitoes, fl ies, midges, gnats, and ticks. Approximately one-third of the U.S. population and 200 million people worldwide use DEET in some form each year; it is also used on dogs, cats, horses, and other animals. DEET is available in various liquids, lotions, sprays, and impregnated materials such as wrist bands.
Formulations registered for direct human application contain from 4% to 100% DEET.
DEET was developed as a joint eff ort by the Department of Defense and U.S. Department of Agriculture (USDA). After examining hundreds of compounds for their repellent capabilities in the 1940s, DEET was selected and patented by the U.S. Army in 1946. Th e USDA did not announce DEET’s discovery until 1954, and it was registered for public use in 1957. DEET is prepared from m-toluoyl chloride and diethylamine in benzene or ether.
DEET | 99
Insects are attracted to people by visual, thermal, and olfactory stimuli. Visual stimuli are more important for attraction at greater distance, with thermal and olfactory being more important at closer range. Humans emit several hundred volatile compounds directly from the body and breath during metabolism. Two compounds thought to attract mosquitoes are carbon dioxide and lactic acid. Carbon dioxide is exhaled with each human breath and lactic acid is a component of sweat. Chemoreceptors on mosquitoes’ antennae are stimulated by lac-tic acid. Although the exact mode of action for DEET is unknown, it is believed that DEET works by disrupting the olfactory senses of the target insect. DEET also is thought to aff ect insect lactic acid chemoreceptors, interfering with its ability to locate the host.
Th e amount of insect protection from DEET depends on its concentration, the host (for example, whether the host is male or female), sweat production, and environmental factors such as wind, temperature, and rain. DEET is sold in formulations that range from a few per-cent up to 100%. Higher conper-centrations of DEET are no more eff ective than lower concen-trations but provide longer lasting protection. A 5% DEET repellent lasts for about an hour, a 15% solution lasts about 3 hours, a 25% DEET formulation should provide about 5 hours of protection, and a 100% DEET should protect for about 12 hours. Health concerns have been raised about the use of DEET, especially when used frequently and in high concentrations.
Studies on rats subjected to high prolonged exposure indicated destruction of brain neurons that control muscle movement, learning, memory, and concentration; rats treated with doses similar to that used by humans showed much less ability to complete motor control and strength tasks than control rats. DEET absorption through the skin depends on its concentra-tion and other chemicals used in combinaconcentra-tion with DEET formulaconcentra-tions; absorpconcentra-tion ranges between a few a percent up to 20%. DEET distributes into the skin and fat tissue (owing to its lipophilicity), where in the lower skin layers it is absorbed into the body. It is metabolized and excreted in the urine within 12 hours after removal from the skin.
An important aspect raised about skin absorption of DEET is its health eff ects when used in combination with sunscreens. Animal and in vitro studies indicate that sunscreen or certain sunscreen ingredient such as oxybenzone increase DEET’s absorption into the skin.
Researchers performing the studies have recommended further research to determine the potential health eff ects of DEET acting in combination with sunscreens. Th e medical commu-nity and government health agencies such as the Centers for Disease Control and Prevention recommend that repellents and sunscreens should be applied as two separate formulations rather than combined in a single product. Th e reason for this is that sunscreens are often applied repeatedly, which could result in much more DEET being used than is needed for protection. Because physicians recommend that only enough repellent be applied to provide the necessary protection, using individual products for sun and insect protection helps ensure against excessive DEET application.
DEET use on children under the age of two months is not recommended. Th e American Academy of Pediatrics recommends that DEET repellents should not be applied more than once per day on children and that the maximum DEET concentration used be no more than 30%.
Spraying on hands, under clothing, and in the vicinity of food is not recommended. Th e Academy also recommends against using combined sunscreen-repellent formulations.
Th e threat of West Nile virus has led government agencies to recommend the use of DEET repellents. West Nile virus is a mosquito-borne infectious disease that is common in Africa, west Asia, and the Middle East; it was fi rst detected in North America in 1999.
100 | Th e 100 Most Important Chemical Compounds
People infected usually experience only mild fl ulike symptoms, but West Nile virus can result in life-threatening encephalitis or meningitis. DEET is the most popular pesticide used as a repellent for humans, with several hundred products containing DEET available in the United States. Because it is a pesticide, products containing DEET are required to be labeled with information concerning the method of application, directions for medical attention, list special precautions for children, and the percent DEET in the product. DEET is still available at 100% strength in the United States, but Canada bans formulation that are more than 30%
and various groups have recommended that this standard be used in the United States.