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Chemistry 101 Fall 2019

Introduction to Environmental Chemistry

Instructor Dr. Upali Siriwardane (Ph.D. Ohio State)

E-mail: upali@latech.edu Phone: 318-278-2272

Tests on Following days

September 16, 2019 : Test 1 (Chapters 1-3)

October 9, 2019 : Test 2 (Chapters 4- 6)

November 4, 2019 : : Test 3 (Chapters 7-9)

November 24, 2019 : Test 4 (Chapters 10-12)

December 4 , 2019 : Final Exam: Chapters 1-12).

1

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A Project of the American Chemical Society

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Chapter 10: Manipulating Molecules and

Designing DrugsIs our society becoming dependent on prescription drugs?

How harmful are illicit drugs?

Herbal remedies: Is “natural” safer than synthetic?

How are effective drugs designed?

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A Wonder Drug?

White willow tree

The classic white willow tree, Salix alba, provides more than just shade and shelter for nature’s animals.

Salicin is the key ingredient that is isolated from the tree and converted into one of our most reliable and heavily used drugs, aspirin!

It is used as an antipyretic-fever reduction.

It is used as an analgesic-pain reliever, and as an anti-inflammatory agent.

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AspirinSemi-synthesis of aspirin: from natural product to marketed drug

White willow tree

Possible side effects:1.Heartburn2.Nausea3.Reye’s Syndrome4.Ringing in ears5.Rash, itch 6.Shortness of breath

Would this drug make it through FDA scrutiny today?

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Carbon Compounds

Organic Chemistry—The Study of Carbon Compounds

There are over 12 million known organic compounds.

Why carbon? Carbon has the remarkable ability to bond in multiple ways:

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Molecular Structures

Some different ways to represent molecular structures:

n-butane and isobutane are isomers, molecules that have the same chemical formula, but with different structures and properties

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Molecular Structures (2)

Representing molecular structures with line-angle drawings:

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Molecular Representations

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Molecular Representations (2)

Representations of benzene (C6H6), an important part of many drug molecules.

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Functional GroupsFunctional groups—arrangements of groups of atoms which impart characteristic physical and chemical properties.

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Functional Groups (2)More Important Functional groups

The presence and orientation of functional groups are responsible for the action of all drugs. See Chapter 9 for more info on functional groups.

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Functional Groups (3)

Ester Formation

Ester functional groups are often found in drugs, flavorings, and fragrances.

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Functional Groups (4)

What are the functional groups in the aspirin molecule?

1. Benzene ring

2. Carboxylic acid

3. Ester

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Polar MoleculesExamples of polar molecules

Functional groups may impart a polar aspect to a molecule.

A polar molecule has partial charge separation.

d- = “partial negative” d+ = “partial positive”

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Salt Formation

The salt forms are often preferred as drugs because of:• Increased water solubility• No odor• Higher melting points (longer shelf life)

CH CH NH

CH3OH CH3

CH CH NH2Cl-

CH3OH CH3

H Cl+

Pseudoephedrine

freebase Pseudoephedrine

hydrochloride salt

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Hormones and EnzymesHormones, our chemical messengers, are produced by the body’s endocrine glands.

Hormones encompass a wide range of functions and a similarly wide range of chemical composition and structure.

Enzymes are proteins that act as biochemical catalysts, influencing the rates of chemical reactions.

Aspirin works by inhibiting the production of certain enzymes responsible for producing specific hormones.

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Aspirin (2)Aspirin and other drugs that are physiologically active, but not anti-infectious agents, are almost always involved in altering the chemical communication system of the body.

Aspirin, as well as other non-steroidal anti-inflammatory (NSAID) drugs, work by inhibiting the catalytic activity of certain enzymes.

The mode of action is due to the ability of aspirin to block the action of cyclooxygenase (COX-1 and COX-2) enzymes from producing the hormonal compounds called prostaglandins.

Certain prostaglandins are responsible for the body’s response to pain, inflammation, and fever.

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Aspirin (3)

Prostaglandins cause a variety of effects. They produce fever and swelling, increase sensitivity of pain receptors, inhibit blood vessel dilation, regulate the production of acid and mucus in the stomach, and assist kidney functions.

By preventing COX-2 enzymes from catalyzing prostaglandin production, aspirin reduces fever and swelling. It also suppresses pain receptors and so functions as a painkiller.

But the drug (as do other NSAIDs) also inhibit COX-1 enzymes that primarily make hormones that maintain proper kidney function and keep the stomach lining intact.

Thus, NSAIDs drugs are not sufficiently selective to affect COX-2 without shutting down COX-1 as well.

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Aspirin (4)

Researchers raced to create nearly a dozen new candidate drugs that block COX-2 alone. This work resulted in the emergence of a new class of medicines in the late 1990s called COX-2 inhibitors.

Two wildly popular and heavily prescribed COX-2 inhibitors are Vioxx and Celebrex. These new “super aspirins” were touted as being safer and more effective than currently available NSAIDs. The premise is that since they do not act on the COX-1 enzymes, there should be fewer gastrointestinal (GI) side effects.

The reality is that they have not been proven to be more effective or safer than aspirin or ibuprofen. In fact, they have been proven to be more dangerous than helpful.

Use the Web to write a short essay on the life and death of “super aspirins.”

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Two COX-2Inhibitors

Uncertain future for the COX-2 inhibitors is due to emerging evidence of their questionable safety. As of 2008, they have been pulled off the shelf by their manufacturers.

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Aspirin (5)

Aspirin, revisited – mode of action

COX enzymes

Prostaglandin production

COX -1: liver function, stomach lining

COX-2: fever, pain sensation, inflammation

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Drug Discovery—Serendipity

Actual photo of petri dish Fleming showing inhibition of growth of bacteria where penicillin landed on the dish.

Sir Alexander Fleming, British bacteriologist

Working with Staphylococcus-a bacteria.

A colleague working in same building was working withPenicillium notatum-a fungus that produces penicillin.

Series of chance occurrences, and penicillin was discovered.

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Drug Discovery—Serendipity (2)

How many functional groups can you identify in the structureabove?

“In the fields of observation, chance favors only the prepared mind”

-Louis Pasteur

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Classification of Drugs

Drugs may be broadly classified as:

1.Those that cause a physiological response in the body.

aspirin

anticancer drugs

morphine

2. Those that kill foreign invading organisms.

antibiotics

antifungal agents

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Drug Interactions at the Cellular Level

The lock and key model.

A substrate is a substance whose reactions are catalyzed by an enzyme. Here you see a drug occupying the receptor site of the natural substrate.

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Functional Groups (5)

The functional groups and their placement in three-dimensional space determines to a large degree a molecule’s biological activity.

The portion of a molecule that determines the biological effects of a drug is called the pharmacophore.

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Combinatorial ChemistryCombinatorial chemistry is the systematic creation of large numbers of small molecules in “libraries” that can be rapidly screened in vitro for potential new drugs.

The benefits of using combinatorial chemistry: 1. Many molecules can be created at a rapid rate.2. The cost of the procedure is much cheaper than traditional molecule synthesis.3. Large libraries of bioactive lead compounds can be produced relatively

inexpensively.

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EnantiomersChiral molecules have 4 different groups attached to a central atom.

A chiral molecule and its non-superimposable mirror image are a special kind of isomer called enantiomers.

Enantiomers have identical physical properties.

The only way we can tell them apart is by seeing their effect on plane-polarized light.

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Enantiomers (2)

However, the body can tell them apart. These two enantiomers may have very different actions in the human body.

One enantiomer fits into a receptor site, while the other does not. The molecule on the right will have (possibly) no affect on the human body.

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Enantiomers (3)

Consider the two enantiomers above. Dextromethorphan is a safe cough suppressant. Levomethorphan is an addictive opiate.

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SteroidsSteroids perform many functions in the body:

A B

C DThis is the basic carbon skeleton for all steroids.

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Functional Groups in Some Common Steroids

Can you identifythe functional groupsin the other examples?

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Prescription, Generic, and Over-the-Counter Medicines

A generic drug is chemically equivalent to the pioneer drug, but cannot be marketed until the patent protection on the pioneer drug has run out after 20 years.

The lower priced drug is commonly marketed under its generic name, in this case alprazolam instead of Xanax.

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Common Herbs and Their Possible Benefits

St. John’s Wort

Herb of Plant Symptoms to Be Relieved

Valerian, passion flower Anxiety

Licorice, wild cherry bark, thyme Coughs

Echinacea, garlic, goldenseal root Colds, flu

St. John’s wort Depression

Chamomile, peppermint, ginger Nausea, digestive problems

Valerian, passion flower, hops, lemon balm Insomnia

Ginkgo biloba Memory loss

Valerian, passion flower, kava kava,Siberian ginseng

Stress, tension

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EphedraEphedra—used safely for thousands of years as herbal remedy known as Ma Huang.

In 2003, several deaths related to the ingredients led the FDA (in 2004) to ban ephedra products. At this time, there are ongoing discussions to make the product available again.

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Ephedra (2)

The herb contains the amphetamine-like alkaloids—ephedrine and the less active pseudoephedrine.

Pseudoephedrine is used as a decongestant

Ephedrine is a bronchodilator (opens the airways), and a stimulant

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Drugs of AbuseClass Has Current Accepted

Medical UsesPotential for Abuse

Examples

Schedule I No High HeroinLSDMarijuana*MescalineMDMA (“ecstasy”)

Schedule II Yes High Oxycodone (in OxyContin and Percocet)Morphine, opiumMethadoneCocaine (as a topical anesthetic)Methamphetamine

Schedule III Yes Medium Hydrocodone with acetaminophen (Vicodin)Codeine with acetaminophenAnabolic steroids

Schedule IV Yes Low Alprazolam (Xanax)Propoxyphene and acetaminophen (Darvocet)Diazepam (Valium)

Schedule V yes Lowest Cough suppressants with small amounts of codeine diphenoxylate and atropine (Lomotil)Promethazine (Phenergan)

*Legal status of marijuana currently complicated because federal and state laws may differ.

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Marijuana: Cannabis sativa

THC, or delta-9-tetrahydrocannabinol is the active drug in marijuana.

Medical uses continue to be argued; the Federal Government is opposed.

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Oxycodone

OxyContin contains oxycodone

Oxycodone has been used safely for many years.

But this formulation includes a time-released mechanism for long-lasting treatment of chronic pain.

Drug abusers quickly determined how to get around the time-release and were able to rapidly ingest large amounts of oxycodone. The effects were said to be similar to heroin.

Over-prescribed in the Appalachian areas in late 1990s and early 2000s.

Many became addicted.