Rosalind Franklin and the Structure of DNA

Three men, James Dewey Watson,  Francis Harry Compton Crick and Maurice Hugh Frederick Wilkins, shared the The Nobel Prize in Physiology or Medicine 1962 "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.", that is, they  modeled DNA as a double helix, each strand of the helix has a backbone of  sugar molecules held together by phosphate groups. The two strands are twisted together and held together by hydrogen bonds. But how did they learn what DNA was made up of?

 This is where Rosalind Elsie Franklin enters the story of DNA. In 1951 she was a Research Associate at Kings College London where she worked on  X-ray diffraction studies with her colleague Maurice Wilkins. Her x-ray diffraction images of DNA led to the discovery of the DNA helix. The image on the left is known as "photograph 51" and was an x-ray diffraction image of DNA obtained by Franklin's Ph.D student Raymond Gosling.

X-ray diffraction is an instrumental technique used to elucidate the structure of crystals of chemical compounds. Incoming x-rays are diffracted by the crystal lattice and they exit the crystal at different angles. An x-ray crystallographer like Franklin can measure the angles and intensities of these diffracted x-rays to produce a 3-dimensional picture of the density of electrons in the crystal lattice. The electron density can then be used to determine the locations of atoms within the crystal lattice.

Without Franklin's knowledge, Maurice Wilkins showed this image to James Watson who used it, along with other evidence, to develop a model of DNA. Science historians still debate whether Franklin would have determined the structure of DNA on her own had her images not been shared with Watson.

Rosalind Franklin made important scientific contributions, not only to the discovery of the structure of DNA and RNA, but also in helping us to understand the structure of viruses, coal and graphite.
Unfortunately, Rosalind Franklin died of ovarian cancer in 1958. Nobel Prizes are not generally awarded posthumously so her contribution to the elucidation of the structure of DNA is not well-known.


Further Reading:
Chemistry of DNA
Intramolecular Forces
Intermolecular Forces

Suggested Study Questions:

1. Explain the terms crystalline and amorphous.
2. Give an example of a crystalline substance and an example of an amorphous substance.
3. Explain why DNA had to be crystallised before useful information could be obtained using x-ray diffraction.
4. What does the abbreviation DNA stand for?
5. What are the 4 principle bases that make up DNA?
6. These principle bases occur in pairs; what are these 2 pairs?
7. What kind of chemical bonds act between the atoms making up each base in a strand of DNA?
8. What kind of chemical forces join one of the bases on one strand of DNA to its corresponding pair on the other strand of DNA?
9. If you wanted to separate the 2 strands of a DNA double helix, what sort of chemical bonds would you need to break?
10. If you wanted to separated each base from the backbone of sugar molecules, what sort of chemical bonds would you need to break?

Explosive Medicine

You’ve probably heard of Alfred Nobel, the inventor of dynamite and gelignite. The commercialisation of these explosives enabled him to accumulate great wealth during his lifetime which, by the terms of his will signed in 1895, was used to establish the Nobel Prize. In later life he was prescribed Trinitrin, a medication used to relieve a heart condition known as angina.

What do dynamite, gelignite and Trinitrin all have in common?

They all contain nitroglycerin!

This is not a story about the life of Alfred Nobel.

It is a story about the fascinating chemistry of nitroglycerin…

Read more in the June 2018 issue of AUS-e-NEWS, AUS-e-TUTE's free quarterly newsletter for chemistry students and teachers.

Subscribe to AUS-e-NEWS at https://www.ausetute.com.au/ausenews.html

Molecular Machines

People use machines to perform tasks that fall beyond our capacities.

Since the Industrial Revolution, the complexity and number of machines we use has increased.

At the Annual Meeting of the American Physical Society in 1959, physicist and 1965 Nobel Laureate in Physics, Richard Feynman talked about the possibility of building small machines from atoms.

He returned to this idea in a lecture in 1984 he asked, "How small can you make a machine?".

But by then Chemists had already taken the first tentative steps towards building molecular machines.

The 2016 Nobel Prize in Chemistry has been awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa, whose research has led to the development of molecular machines...

Learn more in this edition of AUS-e-NEWS.

Visit http://www.ausetute.com.au/ausenews.html to subscribe to AUS-e-NEWS, AUS-e-TUTE's free quarterly newsletter.

2015 Nobel Prize in (Bio)chemistry?

The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for "mechanistic studies of DNA repair".
Cells have developed mechanisms to repair damaged DNA. Four of these mechanisms are:

• photoreactivation


• dark repair (nucleotide excision repair)


• base excision repair


• mismatch repair

Photoreactivation
In the 1920s Hermann Muller found that X-rays could mutate and kill cells.
In the 1940s Albert Kelner found that visible light could stimulate growth recovery after damage caused by UV light, and this was called photoreactivation.
In 1944 Oswald Avery and co-workers showed that DNA is the material of heredity, and in the 1950s it was recognised that DNA became damaged when exposed to UV light.
Renato Dulbecco suggested photoreactivation was an enzymatic reaction dependent on light, which was demonstrated by Stanley Rupert.
In 1978 Aziz Sancar cloned the E. coli photolyase gene, an enzyme responsible for DNA repair in escherichia coli.
In the 1980s Aziz Sancar showed that photolyase can convert the energy of an absorbed photon into chemistry that produces a localised free radical that initiates thymine dimer splitting.

Dark repair (nucleotide excision repair)
In the 1960s Jane Setlow and Richard Setlow showed that thymine dimers inactivated transforming DNA in Hemophilus influenzae and that this was responsible for the biological effect of UV light.
In 1964 Richard Setlow discovered that thymine dimers disappeared from the irradiated, high molecular weight genomic DNA shortly after exposure to UV light and appeared in the low molecular weight fractions, that is, thymine dimers are excised (removed) from the DNA. This mechanism became known as nucleotide excision repair (NER).
In the 1970s Aziz Sancar working with W. Dean Rupp, developed the Maxicell technique for the rapid identification of proteins.
In 1983 Aziz Sancar used purified proteins to reconstitute essential steps in the nucleotide excision repair (NER) pathway, a "cut and patch" method for DNA repair.
Two proteins (UvrA and UvrB) track along the DNA, UvrA recognises damage and causes UvrB to stop tracking and begin unwinding the effected DNA section. Another protein, UvrC, causes the damaged section to be cut out, and then another protein UvrD, causes UvrB to bind and bridge the gap while it is repaired by resynthesising the removed segment via Pol I.

Base excision repair
In the 1970s Tomas Lindahl showed that DNA has limited chemical stability and that modification of the bases of DNA increased the risk of mutations. High levels of spontaneous cytosine deamination leads to the formation of uracil.

Uracil forms base pairs with adenine, so, high levels of cytosine demanination pose a risk of depleting the genetic material from cytosine-guanine base pairs and replacing them with thymine-adenine.
He identified the E. coli uracil-DNA glycosylase (UNG) as the first repair protein which we now know is one member of a large family of proteins that orchestrate base excision repair (BER).
A DNA glycosylase recognises and cuts the base-deoxyribose glycosyl bond of a damaged nucleotide. DNA glycosylase kinks the DNA and the abnormal nucleotide flips out and is removed and the section can then be repaired.

Mismatch repair
During the synthesis of a new DNA strand, a non-Watson-Crick base pair may be formed which distorts the double-stranded DNA helix. These types of errors are known as mismatches.
In 1983 Paul Modrich and Matthew Meselson showed that DNA methylation directed strand-specific elimination of mismatches in E. coli. Modrich developed an assay to isolate the products of the different repair genes and identify the proteins.

Further Reading:
http://www.ausetute.com.au/dna.html
http://www.ausetute.com.au/enzymes.html

Suggested Study Questions:

1. What does the abbrevaition DNA stand for?
2. What do you think when biochemists refer to damaged DNA?
3.  What is meant by the term enzyme?
4. Why do you think enzymes are required in the mechanisms available within a living cell to repair damaged DNA?
5. What is a free radical?
6. Draw the structural formula of thymine.
7. Draw the structural formula for a possible dimer of thymine.
8. What is meant by the term nucleotide?
9. With reference to DNA, what is meant by a base pair?
10. Show how uracil forms a base pair with adenine.
11. Draw the structure of a cytosine-guanine base pair
12. What do you think is meant by the statement, "cytosine deamination leads to the formation of uracil" (structural formulae may be useful in your explanation but you do not need to include chemical reactions).

Nanoscopy

The Nobel Prize in Chemistry for 2014 has been awarded to Eric Betzig, Stefan W. Hell and William E. Moerner for the development of super-resolved fluorescence microscopy. This technique allows scientists to view objects at the nanometre scale and is therefore referred to as nanoscopy.

Since the 17^th century, we have been able to peer into the world of very small things using optical microscopes. In 1873, microscopist Ernst Abbe published an equation to show that optical microscopes could not be used to investigate things that were less than half the wavelength of light, that is, to be seen in an optical microscope the object must be greater than 0.2µm. An optical microscope can therefore be used to see some surface structure of a human hair, but you couldn't use it to see the actual protein building blocks making up the hair.

Stefan Hell was working on fluorescence microscopy, using fluorescent molecules to image parts of a cell. A brief pulse of light makes the fluorescent molecules glow temporarily, following the glow allows scientists to map where the molecules are in the cell. The technique can be used to tell where DNA is located for instance, but it could not be used to determined its structure. Stefan Hall proposed a new method, Stimulated Emission Depletion (STED) in which one pulse of light excites all the fluorescent molecules while another pulse quenches the fluorescence from all the molecules except those in a nanometre-sized volume in the middle. Only this volume is registered. An image is built up be sweeping along the sample and continually measuring light levels. In 2000 Stefan Hall was able to demonstrate the effectiveness of the STED microscope by imaging an E.coli bacterium at a resolution that could never be achieved using an optical microscope.

The nanoscopy method proposed independently by Eric Betzig and W E. Moerner, Single-Molecule Microscopy differs in that it relies on the the superposition of several images.

In 1989, W E. Moerner measured the light absorption of a single molecule for the first time.
W E. Moerner had found that one variant of green fluorescent protein (extracted from fluorescent jellyfish) could be made to fluoresce with light of 488nm wavelength, but that after awhile, the fluorescence faded and would not fluoresce again using 488nm light. The same protein, when hit by light of wavelength 405nm could be brought back to life, and then would fluoresce again when hit with light of 488nm.

In 2006 Eric Betzig demonstrated the usefulness of Single-Molecule Microscopy using a glowing protein coupled to a cell's lysosome. Using a weak light pulse, only some of the molecules were caused to fluoresce, and these were at distances greater than 0.2µm. This image was registered. When the fluorescence of these molecules died out, a new weak light pulse was used to initiate the fluorescence of a few more molecules.This new image was registered. This process was continued many times. When Betzig superimposed all the images, a super-resolution image of the cell's lysosome membrane was the result.

Nobel Prize in Chemistry 2013

Martin Karplus, Michael Levitt and Arieh Warshel have been awarded the 2013 Nobel Prize in Chemistry "for the development of multiscale models for complex chemical systems", that is, they have made it possible to model complex chemical reactions using computers.

When light hits the retina in your eye, the free electrons in retinal are filled with energy, which changes the shape of the molecule. This is the first stage in the process of your sense of sight.
In 1972, Karplus and Warshel modelled retinal by developing a computer program that used quantum  physics when it performed calculations on free electrons and then used classical physics for all electrons and all atomic nuclei. This was the first time that anyone had managed to bring about a chemically relevant collaboration between classical and quantum physics.

Enzymes are crucial to life, but in order to simulate the reactions of enzymes, a computer program would need classical and quantum physics to collaborate more smoothly. In 1976 Levitt and Warshel successfully simulated an enzymatic reaction, and this program would work for any kind of molecule.

The use of computers to simulate chemical reactions is increasingly important as a tool for understanding how reactions occur and the paths the reactants take. Computer programs can be used to optimize chemical process in order to produce better solar cells, improve catalysts in motor vehicles, develop more effective drugs, and so much more.

Reference:
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2013/popular-chemistryprize2013.pdf

Further Reading:
Enzymes: http://ausetute.com.au/members/enzymes.html 
Proteins: http://ausetute.com.au/members/proteins.html
 

Nobel Prize Facts 2013

Alfred Nobel was a Swedish Chemist and the inventor of dynamite. The fortune that he made from this during his lifetime, about SEK 31 million (today about SEK 1,702 million or about $265 million), was left in his will to institute the Nobel Prizes. One of these prizes is awarded to "the person who shall have made the most important chemical discovery or improvement". The announcement regarding the award of Nobel Prizes is made in October each year.
While we wait for this years announcement, here are a few facts about the Nobel Prize in Chemistry:

• 104 Nobel Prizes in Chemistry have been awarded since 1901.
• A Nobel Prize in Chemistry was not awarded in 1916, 1917, 1919, 1924, 1933, 1940, 1941 and 1942
• 63 Chemistry Prizes have been given to one Laureate only
• 23 Chemistry Prizes have been shared between 3 Laureates. 
• A Nobel Prize in Chemistry can not be awarded to more than 3 people in each year.
• 162 individuals have been awarded the Nobel Prize in Chemistry (these people are called Laureates).
• 1 person, Frederick Sanger, has been awarded the Nobel Prize in Chemistry twice.
• 4 women have been awarded the Nobel Prize in Chemistry:
  • Marie Curie 1911
  • Irene Joliot-Curie 1935
  • Dorothy Crowfoot Hodgkin 1964
  • Ada Yonath 2009
• 2 Chemistry Laureates have been awarded Nobel Prizes in other areas as well:
  • Marie Curie (Physics 1903, Chemistry 1911)
  • Linus Pauling (Chemistry 1954, Peace 1962)
•  1 person, Linus Pauling, is the only person who has been awarded 2 unshared Nobel Prizes.
• 4  Nobel Prize Families:
  • Marie and Pierre Curie - husband and wife (Physics 1903)
  • Irene Joilot-Curie and Frederic Joliot - husband and wife (Chemistry 1935)
  • Hans von Euler-Cheplin (father, Chemistry 1929) and Ulf von Euler (son, Medicine 1970)
  • Arthur Kornberg (father, Medicine 1959) and Roger D. Konberg (son, Chemistry 2006)
• Average age of all Chemistry Laureates is 57
• Youngest Chemistry Laureate was Frederic Joliot who was 35 years old when awarded his Nobel Prize in 1935 (together with his wife Irene Joliot-Curie)
• Oldest Chemistry Laureate was John B. Fenn who was 85 years old when he was awarded the Nobel Prize in Chemistry in 2002.
• 0 posthumous Nobel Prizes in Chemistry. A Nobel Prize cannot be awarded posthumously unless death occurred after the announcement of the Nobel Prize.
• 2 Nobel Laureates in Chemistry have been forced by authorities to decline the Nobel Prize. Adolf Hitler forbade Richard Kuhn (Chemistry 1938) and  Adolf Butenandt (Chemistry 1939) from receiving their Nobel Prizes.

Reference:
http://www.nobelprize.org/nobel_prizes/facts/chemistry/

Nobel Prize countdown

As students head back to the class room for a new term of exciting learning, the scientific community is gearing up for a major annual event, the announcement of the Noble Prizes.
With just days to go before the Nobel Prize in Chemistry is to be announced, there is much discussion (and possibly even a bit of betting) about who is likely to be this year's laureate.

Among the contenders this year are:

• Louis E. Brus (Columbia University) for the discovery of colloidal semiconductor nanocrystals (quantum dots)
• Akira Fujishima (University of Tokyo) for the discovery of photocatalytic properties of titanium dioxide (the Honda-Fujishima Effect)
• Masatake Haruta (Tokyo Metropolitan University) and Graham J. Hutchings (Cardiff University) for their discoveries of catalysis by gold

Quantum dots are semiconductors, but their electronic properties are related to the size and shape of the individual crystals. In general, the smaller a crystal is, the more energy is needed to excite the dot, which means that more energy is released when the crystal returns to its ground state. It is hoped that quantum dots will lead to practical quantum computing and increase the efficiency of photovoltaic cells. Quantum dots are being used in preference to some dyes in biological analyses because quantum dots are brighter and more stable.

While working on his Ph.D in 1967, Akira Fujishima exposed a titanium dioxide electrode to strong light and discovered that this catalyzed the decomposition of water into hydrogen and oxygen. This became known as the Honda-Fujishima Effect (Professor Kenichi Honda was Akira Fujishima's supervisor). Finding cheap, effective methods for providing hydrogen would enable the development of hydrogen as fuel.

In the 1980's Masatake Haruta showed that colloidal gold, gold clusters with diameters of 5 nanometers or less, could catalyze reactions involving oxygen gas.
Graham J Hutchings has extended the number of reactions  we now know of that can be catalyzed by gold. Hutchings has shown that primary alcohols can be oxidized to aldehydes using a gold-palladium/titanium dioxide combination without the need for a solvent. He has also developed the rapid synthesis of hydrogen peroxide, H₂O₂, from hydrogen and oxygen  without the formation of water as a by-product.

Nobel Prize for Work on Graphene

The 2010 Nobel Prize in Physics has been awarded to Andre Geim and Konstantin Novoselov for their "groundbreaking experiments regarding the two-dimensional material graphene".

Graphene is an allotrope of carbon, it is the thinnest and strongest material known. It conducts electricity as well as copper and outperforms all other materials as a conductor of heat. It is almost completely transparent, yet it is so dense that not even helium, the smallest known gas atom, can pass through it.

Geim and Novoselov extracted graphene from a piece of graphite such as is found in "lead" pencils. Using a piece of adhesive tape they obtained a flake of carbon that was just one atom thick, which is the allotrope known as graphene.

Reference:
http://static.nobelprize.org/nobel_prizes/physics/laureates/2010/info_publ_phy_10_en.pdf

Further Reading
Allotropes
Elements

Study Questions:

1. What is meant by the term allotrope?
2. Name two other naturally occurring allotropes of carbon.
3. Draw a table listing the physical properties of both of these allotropes and graphene.
4. Discuss the similarities and differences between these allotropes.
5. Draw a possible structure for graphene.
6. Describe the similarities and differences between the structure for graphene that you have drawn and the structures for the other two allotropes in your table.
7. Using your structure for graphene, explain the similarities and differences between the physical properties of graphene and the other two allotropes.