molecules of the week (general chemistry lab prelab talk)

Created by Conrad T. Pfeiffer, Graduate Student, Temple University, June 10th 2014 Adapted from chapters from Napoleon's Buttons: How 17 Molecules Changed History by Penny Le Couteur and Jay Burreson Structures drawn using ChemDraw

Week 1: “Phenol” and “Phenols”

Prior to the 1860s an overwhelming about of

patients undergoing surgery died of post-op infections to

the point most considered surgery as a last option. Around

this time, the idea that small microorganisms (germs)

caused disease was only a theory and not commonly

accepted. Inspired by a paper on “The Germ Theory of

Diseases” by Louis Pastuer (of milk pasteurization fame),

Joseph Lister began to investigate the use of substances to

prevent infection by application to the surgical wound

dressings. He found that an application of “carbolic acid”

to a child’s leg following the repair of a compound fracture

was able to ward infection.

Carbolic acid was isolated from the coal tar that

was a byproduct of the many gas lamps used to light city

streets. Phenol was found to be the main constituted in

the carbolic acid that Lister used. By 1867, he was using

carbolic acid as an antiseptic with much success. Lister

also pioneered many other advances in “sterile surgery”. Phenol is not used as an antiseptic anymore as

prolonged exposure was found to be toxic and lead to illness.

“Phenols” constitute a class of organic molecules found both in nature and synthetically. Shown

here are a few examples.

Perhaps the most powerful gift that phenol has given humanity is its use in the development of

the first plastic. In 1907, Leo Baekeland was searching for a replacement of “shellac”, which is a chemical

secreted by a beetle in South America, for use in devices such as insulators. In time, he found that by

controlling the temperature and pressure during a thermosetting reaction between phenol and

formaldehyde, he could produce an insoluble resin that took the shape of its container. He called this

resin Bakelite, patented the process and started a successful business. This marked the birth of the

plastics industry!

OH

Phenol

Antiseptics: Explosives: Food Flavoring:

Drugs (Legal and Illegal):

OH

ClCl

Cl

OH

OH

C6H13

OH

NO2O2N

NO2

trichlorophenol hexylresorcinol trinitrophenol

OH

OMe

CHO

vanillin

OHO

OH

O

OH

OH

OH

OOH

OH

OH

OMe

Me

Me

OHOH

epigallocatechin-3-gallate

tetrahydrocannabinol

active compound in marijuana

found in green tea and red wineprevents buildup in arteries (heart

disease)

primary extract from vanilla beanfireworks and munitionsprevents infectionsnot used anymore

carcinogenic

Plastics:

OH

H H

O+

heat

pressure

OH OHHO

OH

OH

while in mold


Week 2: Spice and the Age of Discovery

Many of us were taught in grade school that “In 1492, Columbus

sailed the ocean blue” and some of us may even remember why: He was

searching for a route to the East Indies! This time period is often called

the Age of Discovery and it was fueled by one thing – money! More

specifically, money from trading with Eastern Asian countries for the

spices that grew there. One spice in particular stood out a little more

than most – pepper.

First introduced to Europe by Arabian traders in Damascus,

pepper was used as an antidote to poison by the Greeks as early as the

5th century B.C and later by the Roman Empire as a spice in many foods.

During the Age of Discovery, a small spice supply by land caused pepper

to first be a luxury item in most of Western Europe. This did not last long,

however, as the masses began to clamor for the spice. Without

refrigeration, most meat was sold heavily salted to help slow it from spoiling. Pepper quickly became the

choice way to make the heavily salted food more appetizing. The chemical responsible for the “hot”

sensation of pepper from India is piperine and this sensation is not a “taste” but actually a dull pain

caused by piperine binding to pain receptors in your mouth. This pain causes neurotransmitters called

endorphins to be released in the brain which in turn gives a feeling of pleasure.

Now, as well all know, Columbus never reached the Far East but instead discovered the West

Indies and another spice very similar to the Indian pepper – the chili pepper (and thus capsaicin). In the

16th century, the East India Company was founded (you may have noticed their presence in the Pirates

of the Caribbean movies). The idea of the company was that because of the risk of sailing to bring spices

to Europe, each merchant could bid for a “share” of the overall profit. This protected each individual

merchant from unrecoverable losses and lead to the modern day stock market and the basis of

capitalism!

Other related spices such as cloves, nutmeg and ginger were also highly desired from the Far

East as well. An island very rich in nutmeg groves became the scene of intense fighting between the

English and the Dutch that lead to the 1667 Treaty of Breda. As part of this treaty, the English gave full

control of the island to the Dutch and in return the Dutch gave up control of an island in the “New

World” – the island of Manhattan! Had this spice been not so valuable, “New York City” would have

been “New Amsterdam City”!

O

O

O

N

MeO

HO

NH

O

MeO

HO

MeO

HO

MeO

HO

O

Piperine

Capsaicin

Eugenol Isoeugenol

Zingerone

Black and White Pepper (India)

Chili Peppers (West Indies)

Cloves Nutmeg

Ginger


Week 3: Ascorbic Acid and the Open Sea

We now know that the Age of Discovery was driven by a

profitable spice trade with the Far East. As a consequence, stronger

ships were built to survive the open ocean and enabled explorers to

sail far and wide to claim new lands and resources for king and

country. This travel was harsh on the sailors as life aboard the ship

was difficult. Surprisingly the biggest killer of sailors was not

shipwrecks or pirates but a disease called scurvy.

Scurvy is caused by a vitamin C deficiency and its symptoms

include dry mouth, exhaustion, weakening of gums, fever, yellowing of

the skin, muscle pain and eventually death. One example of the

magnitude of this disease comes from Magellan’s circumnavigation of

the globe from 1519 to 1522. During this trip, over 90% of his crew was

lost to scurvy. Vitamin C is chemically known as ascorbic acid and is

synthesized within the body of most mammals. Unfortunately, humans

do not have the forth enzyme, called lactonase, needed to make

ascorbic acid from the sugar glucose. Today the modern synthesis of

vitamin C for use as supplements begins with glucose as in nature.

Vitamin C is found in fresh fruits and veggies and it’s deficiency in

sailors in the 15th century can be linked directly to the poor diet aboard the ships. Since these were

wooden ships, they absorbed water through their hulls which caused any bread and fruit to quickly mold

only days after leaving port. Also an effect of being wooden, ships would only have a fire in the galley in

very calm waters. Therefore a crew’s diet consisted almost entirely of heavily salt meat and hardtack (a

very hard bread substitute). To make matters worse for those who had begun to show signs of scurvy,

the weakening of gums made even this poor diet very difficult to eat.

Many cures were claimed by different sailors and surgeons; however, it was not until an

experiment in 1747 by a British Naval surgeon James Lind that proved fresh lemons and oranges as the

best treatment. Captain James Cook of the British Royal Navy was the first to demand his crew eat a

better diet both on land and sea. He added sauerkraut and tea to the ship’s menu and stopped as often

as possible to collect fresh fruits and veggies. Cook was never recorded as losing a crew member to

scurvy. It was not until some 40 years after Lind’s experiments that better diet was require aboard most

ships. Had the value of a balanced diet, specifically with foods containing vitamin C, been recognized

earlier, the world today might be a very different place.

O O

OHHO

HO

HO H

Ascorbic Acid

CHO

OHH

OHH

HHO

OHH

CH2OH

[O]

CHO

OHH

OHH

HHO

OHH

CO2H

Reduc.

CH2OH

OHH

OHH

HHO

OHH

CO2H

lactonaseO O

OHHO

HO

HO H

[O]

O O

OHHO

HO

HO H

Glucose


Week 4: Sugars and Slavery

We first saw glucose as a starting material for the

modern and biological synthesis of ascorbic acid. Glucose can

be drawn both as an open chain (Fisher Projection) and as a

cyclic compound because these two conformations are in

equilibrium. The –OH group at the C2 position can be down (α-

glucose) or up (β-glucose). Emil Fisher (hence Fisher Projection)

determined the chemical structures of all sugars in 1891 in

what some consider the most clever chemical investigation ever

deduced. He won the Nobel Prize in 1902 for this work.

Glucose is one of many sugars and is frequently found

as a component of sweet tasting foods. Like the spices we

discussed before, sugar began as an expensive luxury item that

eventually grew into a dietary staple of the “civilized world” in

the 1800s. This lead to the development of massive sugar

plantations in Brazil and the West Indies and a lead to an influx

of African slaves to the Americas. Most notably, the tobacco

industry is talked about as the driving force behind this influx of

slaves when, in fact, two-thirds of the slaves forced to the “New

World” worked on sugar plantations.

Sugars are found in many natural foods such as honey,

sucrose, and milk, lactose. Both of these sugars are called

“disaccharides” meaning they are two monomeric sugars linked

together. In the case of sucrose, the sugars contained within are glucose and fructose. Sugars act much

like the spices we previously discussed in that they bind to receptors on your tongue with the difference

being these receptors are “taste” receptors and not pain receptors. There are four general types of taste

receptors found on your tongue: sweet, salty, bitter, and sour.

Today, the development and production of artificial sweeteners is a billion-dollar business.

Beginning as early as 1885 with the development of saccharin, many sweet compounds have been

discovered including sodium cyclamate and aspartame. The latter is somewhat controversial because

some humans lack the enzyme needed to metabolize the molecule and so must avoid foods containing

it. Sucrolose was approved by the FDA in 1998 and looks much like a natural sugar save for the three

chlorines in the molecule. Interestingly, these chlorines block this molecule from being metabolized

making it a non-calorific sweetener.

A final interesting story is that the early search for artificially sweeteners may have contributed

to the fall of the Roman Empire. Most historians agree that Rome “rotted from the inside” through

greed, corruption, and general madness but from where did this “madness” come? Perhaps it was the

lust of power, greed of money, the longing of fame, or even the incestuous ways of some of the weathly

families; or, perhaps, it was because of the artificial sweetener in the wine that was all-to-consumed by

those in power….lead acetate! For the record, the effects of lead poisoning include, loss of sleep,

irritation, headaches, and permanent brain damage.


Week 5: Boom goes the Dynamite

Nitro compounds “exploded” onto

the scene in ancient China with the invention

of gunpowder. The first ingredients list

known was as early as 1000 A.D and used

potassium nitrate (KNO3). The first record of

gunpowder in Europe was is 1260 by a

Francisan monk named Roger Bacon. Fearing

its destructive power falling into the wrong

hands, Bacon wrote the recipe for

gunpowder in a code that was not broken

until over 650 years later (and by that time

others had reviled the recipe for

gunpowder). The first firearms were simply a

pipe with a projectile and lit buy a candle or

torch made around 1300-1325.

What is the chemical nature of an

explosion? As you can see by looking at the reaction schemes, the decomposition of a solid or liquid

leads to the formation of many gas molecules. Because this process is highly exothermic, this gas rapidly

expands creating a powerful shock wave. Any solids form create the “smoke” you see after the

explosion. In the case of gunpowder, the shock wave moves as ~100m/s. In comparison, trinitrotoluene,

or TNT, is a much more powerful explosive and produces a shock wave that travels at ~6,000m/s. The

reactions of an explosion are very rapid due to the production of very stable molecules such as N2 and

because a supply of fuel (oxygen) is built into the molecules as –NO2. The oxygen must be bound to

nitrogen to be explosive as shown in the example here.

Nitroglycerin is a powerful explosive liquid that can be made from the nitration of glycerol with

nitric acid. First discovered in 1847 and used as a way to blast through mountains to build railroads,

nitroglycerin is very unstable as a liquid and has exploded to kill many by accident. It was not until 1860s

while working in his family owned nitroglycerin factory that Alfred Bernard Nobel found that he could

stabilize the liquid by suspending it in diatomaceous earth forming a solid to create what is now known

as dynamite!. Nitroglycerin outside of its explosiveness has found use in medicine for diluting blood

vessels to avoid blockage. Nobel made a large fortune on his invention and when he died in 1896 he left

his estate to provide what have become yearly awards in the fields of chemistry, physics, medicine,

literature and peace. The Nobel Prize would not be known were it not for an explosive and the

landscape and war would not be the same without nitro compounds.

NO2 NH2

HO O

C7H7NO2Explosive Not Explosive

NO2 NO2

NO2

NO2

NO2O2N

<<< < <

toluene nitrotoluene dinitrotoluene trinitrotoluene

OH

OH

OH

O

O

O

NO2

NO2

NO2

nitroglyceringlycerol

HNO3

4 KNO3 (s)+ 7 C (s) + S (s) 3 CO2 (g) + 3 CO (g) + 2 N2 (g) + K2CO3 (s) + K2S (s)

Gunpowder:

2 C7H5N3O6 (s) 6 CO2 (g) + 5 H2 (g) + 3 N2 (g) + 8 C (s)

Trinitrotoluene (TNT):

4 C3H5N3O9 (s or l) 6 N2 (g) + 12 CO2 (g) + 10 H2O (g) + O2 (g)

Nitroglycerin:


Week 6: Rubber Meets Road

Natural rubber collect from plants in

Central America have been used by local tribes

for decorative and practical purposes since

between 1600-1200 B.C. Columbus introduced

rubber to Europe upon return of his second

voyage to the New World. However, since

pure, natural rubber becomes sticky and

smelly in hot weather and hard and brittle in

cold weather, it took curious scientific

investigations to unlock the usefulness of the

substance. In 1826, an English scientist named

Michael Faraday established the chemical

formula of the monomeric unit of rubber –

isoprene! With only 5 carbons, isoprene is the

simplest natural polymer known. As you can

see, the structure of isoprene allows rotation to achieve both cis and trans forms. This can lead to the

polymer in a all-cis, all-trans or a mixture form. This leads to different properties since each trans chain

packs tightly against each other it produces a very rigid and hard form of rubber while cis chains can

slide past each other giving a stretching property. As an example, at one time a golfball was made

entirely of rubber – a mostly cis chain core and a mostly trans chain shell.

In 1834 American inventor Charles Goodyear began to work with rubber and in 1839 discovered

that if rubber was heated with sulfur it stabilized the rubber, thus the process of vulcanization. Sulfur

creates disulfide bonds across the chains! Rubber bands contain 1-3% sulfur, tires contain 3-10% and

insulators contain 23-35%. A blockade of Germany during WWI led to a German search for synthetic

rubber which lead to the discovery of Styrofoam (a polymer of styrene) and eventually the development

of synthetic rubber by German company IG Farben. In 1929 (between WWI and WWII), Standard Oil

Company of New Jersey created a business partnership with IG Farben. IG Farben released the patent

only with the exclusion of detailed technical information believing that the US would not be able to

figure it out. We did and the synthetic rubber business boomed by the end of WWII. In 1953, Karl Ziegler

(Germany) and Giulio Natta (Italy) developed catalysts that could control cis/trans chain formation

during the polymerization process and were awarded a Nobel Prize in 1963. Rubber plays a critical role

in our everyday lives. Picture a world not only lacking in tires for our cars and planes but a world without

rubber soled shoes, or many of the gaskets, o-rings, belts and seals needed for our machines!


Week 7: Alkaloids and Addiction

Alkaloids are a group of organic molecules that

contain at least one basic nitrogen. Many alkaloids have

biological effects on the human body. Over 5000 years

ago the opium poppy from Papver Somniferum, native

to the eastern Mediterranean, was used as a medical

herb and appear on the “herbal lists” of many cultures

in the region throughout history - Greeks, Phoenicians,

Egyptians and so on. It was even dosed to teething

infants as a soothing syrup!

Opium contains 24 alkaloids, the most abundant

being morphine at ~10% by weight. First isolated by

Friedrich Serturner in 1803 and structurally determined

in 1925, morphine is a narcotic that numbs sensitivity

and induces sleep. It acts as a mimic of endorphins and

works by blocking a pain receptor in the brain. Codeine is also widely known and is found in opium at

0.3-2%. It acts in the same fashion but is less powerful. Both molecules are very addictive and have been

abused as recreational drugs by themselves but also lead to the development of a much darker drug.

Mirroring prior successfully drug improvements of a different compound, in 1898 Bayer and Company

acylated morphine and began marketing the result as a cough suppressant. It did not take very long until

this was pulled from the market due to being even more addictive than morphine and codeine. Today,

diacetylmorphine is more commonly known by its original trade name – “Heroin”! Heroin crosses the

blood-brain barriers much more easily than its predecessors and then is converted to morphine in the

brain and acts as before, only at a much, much higher concentration!

Another commonly used and abused alkaloid of today was first introduced to the “civilized

world” by Columbus on return from his second voyage to the New World. Tobacco, first found naturally

and used in South American contains at least 10 alkaloids with the most abundant being nicotine and

contained at 2-8% by weight. Initially, nicotine stimulates the nervous system but then acts as a

depressant. It mimics a neurotransmitter but is not cleared from the receptor as quickly. Nicotine is an

insecticide and is fatal to an adult at 50mg. Given this information, it is somewhat surprising that it is

very structurally similar to other alkaloids that are actually essential nutrients – niacin and vitamin B6!

Our last series of alkaloids are almost certainly pumping throughout many of your bodies as we

speak. Caffeine is found naturally in coffee beans and tea leaves. A common misconception about

caffeine is that it “wakes us up”. But in fact, caffeine works by blocking adenosine, which is a

neuromodulator that slows the release of neurotransmitters in the brain thus making us feel sleepy. So

really, caffeine does not “wake us up” but rather just prevents us from “feeling sleepy”. Another

surprise is that caffeine is a toxin and is fatal to an adult at a dose of 10g. Luckily, a cup of coffee

contains only about 80-180mg and a cup of tea 40-90mg. Similar molecules in both structure and

function are found in tea and cocoa. Alkaloids have an even wider function in then shown here. But even

with this small sample, we have seen a pain killer, illegal drugs, legal drugs, essential nutrients and the

active component of the most widely consumed beverage in the world!

O

HO

HO

N

O

O

HO

NO

O

O

N

O

O

Morphine Codeine Diacetylmorphine(heroin)

N

N

H

N

OH

O

N

OH

OH

HO

Nicotine Niacin Vitamin B6

N

N N

N

O

O

N

N N

HN

O

O

HN

N N

N

O

O

Caffeine(coffee and tea)

Theophylline(tea)

Theobromine(cocoa)


Week 8: Molecules of Witchcraft

From the middle of the 14th to the late 18th century, an

estimated 40,000 or even a few million (90% woman) were

accused of witchcraft and burned at the stake. Some witches were

subjected to the “water test”. In this test, the accused would have

their hands bound at their sides and were then tossed into a pond

or lake. If the float, it was considered to be that the devil was

preventing their body from sinking and they were burned at the

stake. If they sank, then they were considered free from sin,

although also now free from the living. Today, many of

Christianity’s holiday rituals actually come from the Pagan rituals

the Church once prosecuted! Some examples are Christmas trees

and mistletoe, painting eggs during Easter, the Roman feast day of

Saturnalia (Christmas Eve) and the great Celtic festival of the dead

(Halloween).

Most “witches” were actually herbalists whose fate was

sealed simply by the time period not being able to chemically

explain their science. When we now think of witches, we may picture an old woman mixing a bubbling

potion of toad and flying on a broomstick! This image may actually have some merit. During this time

period, it was known that a strong poison could be extracted from the venom of a common European

toad. The active compound of this venom is called bufotoxin and is cardiac toxin – one of the most

powerful toxins known! Records of the time show that “flying potion” recipes typically contain one or

more of crushed mandrake, belladonna and/or henbane plants mixed in oil and then applied to the skin.

Common alkaloids are found in these plants – hyoscyamine and hyocine. These molecules, when readily

absorbed through the skin, cause blurry vision, agitation and delirium/hallucinations which may explain

the claim of “flying”. A final molecule is actually a group of molecules – the ergot alkaloids found in the

ergot fungus that can infect many cereal grains such as rye. Specific symptoms depend on the “R” group

of the alkaloid but may include, convulsions, seizures, hallucinations, vomiting, miscarriage during

pregnancy and gangrene onset from decreased circulation. This occurring in a town often lead to the

accusation of a witch’s spell being cast! A number of experts have concluded that ergot poisoning was

the root cause of accusations against some 250 people and 20 murders (mostly women) in Salem,

Massachusetts in 1692 (Salem Witchcraft Trials) that then grew to a deadly game of one person’s power

over another’s life. Passed along in lessons of the “Dark Arts” was useful information of many plant and

animal extracts such as using willow tree extract as a pain reliever, wild celery to prevent muscle cramps

and relieving the symptoms of asthma with ivy. Today’s medical drug market largely consists of

compounds isolated and found in nature or derivatives of such molecules. Without a record throughout

history of herbal remedies and toxins, we would not have many of the medicines of today!

O

Me

OH

HMe

HO

H

O

O

Me

O

O

HN

O

OH

O

HN

NH

NH2

NMe

O

O

OH NMe

O

O

OH

O

Bufotoxin

Hyoscyamine Hyoscine

N

NH

Me

HO

R

Base structure of Ergot Alkaloids


Week 9: The Birth of the Chemical Industry

The extraction and

preparation of dyes, mentioned in

Chinese literature as early as 3000

B.C., may have been man’s earliest

venture in the field of chemistry. The

first dyes were isolated from plants

and colored fabrics through

complicated procedures passed on

from person to person. Colors such

as red and yellow are commonly

found in natural whereas blue and

purple are not – this lead to color of

clothing relating to class and wealth.

One of the rare sources of

blue came from a plant and required

a 2 step process to produce the dye.

A marine mollusk was found to

secret a chemical that would

become a shade of purple when

exposed to air. Purple became the

chosen color of royalty and in some

cases; it was illegal for anyone

outside of the royal family to don the

color. The dye alizarin comes from

the madder plant and must be in the presence of a metal ion to adhere to fabric. Interestingly, the color varies

with different metal ions: aluminum = rose, magnesium = violet, chromium = brownish-violet, calcium = reddish-

purple. Carminic acid is the dye obtained from crushed female cochineal beetles and while first used by the Aztecs

in Central America, is better known for giving the British Army its “redcoats”.

Beginning in the late 1700s the growing dye market moved from collection to manufacture. The first

synthetic dye should look familiar – trinitrophenol – which has some obvious disadvantages as a dye. Nevertheless,

this marks the birth of the chemical industry!!! Working toward the goal of synthesizing the antimalarial drug

quinine from coal tar (the same source where phenol was found!), William Henry Perkin ended up making

mauveine. This dye proved to be colorfast on both silk and cotton. Perkin’s discovery marks the first true multistep

synthesis of an organic compound and quickly leads to advancement in the industry. Perkin’s name is forever

enshrined in organic chemistry books for his work. Germany became an early leader in chemical industry by strong

ties between its chemical companies and academic scientists. When the countries three biggest chemical

companies, BASF, Hoechst and Bayer and Company, formed a giant conglomerate after WWI called IG Farben, they

dominated the chemical industry. During WWII IG Farben would take over any industry within a Nazi occupied

region. After the war, 9 executives were found guilty of plunder and property crimes, four were also found guilty of

imposing slave labor and treating prisoners of war inhumanely. As a result, the powerful conglomerate was broken

apart, however, all three are still very much a player in the chemical industry. The demand for dyes caused the

development of the dye industry and the birth of chemistry in industry. From scientific investigation into dyes

came the discovery of explosives, perfumes, paints, pesticides, ect.

O

OH

HOHO

OH

O

NH

O

OH

HOHO

OH

O

NH

Br

fermentationin base

NH

O

NH

OHN

O

NH

OHN

OBr

Br

indican (colorless) indoxol (colorless) indigo (blue)

bromoindican (colorless) dibromoindican (Tyrian purple)

beta-carotene (orange)

O

O

OH

OH

O

O

OH O

O

HO

alizarin (red)

juglone (brown) lawsone (red-orange)

O

O

HO

OH

OH

OH

OH

echinochrome (red)

O

O

OHMe

HO OH

OHHO O

O

OH

OH

OH

OH

Me

O

O

OHMe

HO OH

OHHO O

O

Me

N

NMe

H2N

Me

NH

Me

OH

O2N NO2

NO2

mauveine (deep purple)

trinitrophenol (yellow)carminic acid (scarlet) kermesic acid (bright red)


Week 10: The Birth of “Big Pharma”

In 1856, the year that Perkin

synthesized mauveine, the average life

expectancy in Britain was ~45 years. By 1900

the average life expectancy in the United

States was around 46 years old for a man and

48 for a woman. In 2000, the life expectancy of

a man was 72 years for a man and 79 for a

woman. What changed? As we learn last week,

Perkin’s synthesis birthed the dye industry. By

meeting the demand, chemical companies

were able to make large profits while

expanding knowledge of the chemical world.

This knowledge led to the discovery of many

other chemical fields, none more important

than the pharmaceutical industry.

In 1893 Felix Hofmann, a chemist

working for Bayer and Company, decided to

investigate the properties of compounds

related to salicin, a molecule isolated from willow tree bark (and a molecule of witchcraft). By screening a series of

molecule, Hofmann found that (by dosing his father) acetyl salicylic acid was an effective pain killer. You may know

his discovery as “aspirin”. German doctor Paul Ehrlich developed the idea of “magic bullet” type drugs as proven

by his discovery of salvarsan as a treatment for syphilis. By “magic bullet” we mean a molecule that will specifically

cure a disease rather than one that targets everywhere in the body. In the 1930s, with her daughter deathly ill,

Gerhard Dogmak, an IG Farben doctor, treated his daughters bacterial infection with prontosil red (which had

shown success in mice by not against bacteria in a test tube). His daughter fully recovered in no time! Researchers

soon realized that the molecule was being broken down in the body and the resulting metabolite was the active

drug and explains why it worked in mice but not in a test tube. Sulfa drugs have been very successful for treating a

wide variety of infections. These types of drugs work by inhibiting bacteria from synthesizing a nutrient essential

for their own survival – folic acid (vitamin B9). Since, we humans cannot synthesize folic acid and must consume it

in our diet; sulfa drugs do not affect our cells.

Louis Pasteur (that name should sound familiar) was the first to show that one organism could be used to

kill another in 1877 by killing a strain of anthrax by adding a strain of bacteria. Later, Joseph Lister (we talked about

him too!) investigated the properties of molds to prevent infection with some positive results. Finally, in 1928 a

Scottish physician named Alexander Fleming discovered a mold had accidentally contaminated bacterial cell

cultures he was studying. He noted that the presence of the mold caused the bacterial colonies to become

transparent and vanish. After further experimentation, he successfully isolated the chemical responsible for the

mold’s activity. Fleming named his discovery “penicillin”; however, at the time it generated little interest and did

not go into clinical trials until 1941. Since the structure of penicillin was unknown, the only way to produce the

drug was to grow and extract it from the mold. This lasted until WWII when 39 laboratories in the United States

and Britain began to work together to determine the structure of the molecule, which they did the year after the

war ended in 1946 and worked out the first synthesis in 1957. Penicillin is an unusual structure in that it has a

highly strained 4-membered ring. As it turns out this ring is very important for the molecules ability to inhibit cell

wall synthesis. I will not summarize the effects these molecules played in the world. I will only ask you to think

about the last time you were ill and prescribed a drug…

molecules of the week (general chemistry lab prelab talk)

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